Remote Monitoring of Axial Spondyloarthritis in Specialist Healthcare Services
Phase: NA
Conditions: Axial Spondyloarthritis
Sponsor: Diakonhjemmet Hospital

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Remote monitoring of axial spondyloarthritis in specialist 
healthcare services (ReMonit) 
 
The ReMonit study 
IDENTIFIER NUMBERS 
 
REK no: 229187 
ClinicalTrials.gov: NCT05031767 
PROTOCOL NUMBER 
Version 1.1 (revised November 2021) 
SPONSOR 
 
 
 
 
 
Sponsor signature & Date: 
Diakonhjemmet Hospital AS  
Contact person:  
Professor Espen Haavardsholm, MD PhD 
Address: Box 23 Vinderen, 0319 Oslo, Norway 
Tel: +4722451500 
E-mail: espen.haavardsholm@medisin.uio.no 
01.11.2021 
 
_____________________________ 
PRINCIPAL INVESTIGATOR 
 
 
 
Principal investigator signature & 
Date:  
Nina Østerås, PT PhD 
Division of Rheumatology and Research 
Diakonhjemmet Hospital 
E-mail: nina.osteras@medisin.uio.no 
01.11.2021 
_____________________________ 
 
 
 

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Protocol amendments in version 1.1: 
 
Amend-
ment 
No. 
Date 
Protocol Section 
Affected 
Reason for amendment 
Expected 
Impact on 
Study 
1 
01.11.21 
Protocol 
Summary + 
5.1.2 Usual Care 
The text regarding the content of the 
conventional follow-up strategy (usual care) 
is revised to be more specific on the content 
of the face-to-face-visits. 
None 
2 
01.11.21 
Protocol 
Summary + 3.2.3 
Intervention 
+ 5. Study 
Intervention 
The text is revised to clarify that the physical 
activity tracker data is collected for the 
purpose of research, that this data is not 
monitored by the project group and that is 
not included in the evaluation of 
intervention compliance. 
None 
3 
01.11.21 
1.3 Schedule of 
Activities 
Medication review is added to the schedule 
of activities for clarification of the content of 
the face-to-face-visits. 
None 
4 
01.11.21 
2.3.4 Objectives 
and endpoints 
The secondary objectives were further 
divided into secondary and additional 
objectives to be more clear. 
None 
5 
01.11.21 
5.1.4 Patient-
initiated care arm 
 
Table 2 regarding indication for the HPs to 
contact a patient in the Remote monitoring 
study arm was updated to be more clear on 
which situations that leads to a “yellow flag” 
or a “red flag”. 
None 
6 
01.11.21 
Protocol 
Summary + 3. 
Overall Design + 
8. Statistical 
Considerations 
The definition of the primary endpoint was 
amended to be more clear. «The proportion 
of low disease activity…» was replaced with 
«The point prevalence of low disease 
activity..» 
None 
7 
01.11.21 
9.5.17 Patient 
satisfaction with 
remote 
monitoring or 
patient-initiated 
care 
We have replaced the instrument Telehealth 
Usability Questionnaire (TUQ) with Service 
User Technology Acceptability Questionnaire 
(SUTAQ) since the SUTAQ is translated into 
Norwegian and validated. 
None 
8 
01.11.21 
References 
The reference for the eHealth Literacy 
Questionnaire (eHLQ) was corrected. 
None 
 
 
 

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Study organization 
Medical Leader 
Inger Jorid Berg, MD PhD 
Principal Investigator 
Professor Nina Østerås, PT PhD 
Project group members 
 
Inger Jorid Berg, MD PhD, Postdoctoral fellow, 
Professor Sella Aarrestad Provan, MD PhD 
Eirik Klami Kristianslund, MD PHD 
Anne Therese Tveter, PT PHD 
Professor Espen Haavardsholm, MD PhD 
Siri Lillegraven, MD MPH PhD 
Joseph Sexton, MSci PhD 
Emil E.K. Thomassen, PT PhD student 
Ellen Moholt, study nurse 
Inger Espegren, study nurse 
Jostein Arnesen, coordinator 
International and national advisors 
Professor Gary Macfarland, MD PhD, Scotland 
Professor Laure Gossec, MD PhD, France 
Assoc. Professor Annette de Thurah, RN PhD, Denmark 
Assoc. professor Gunnstein Bakland, MD PhD, Norway 
Patient representative 
Tale Gjøvik 
Sarah Hakim  
Biostatisticians 
Joseph Sexton, MSci PhD  
 
 

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Table of content 
Protocol amendments in version 1.1: ................................................................................................. 2 
Study organization ............................................................................................................................. 3 
1 
Protocol Summary .............................................................................................................. 7 
 
Synopsis ........................................................................................................................................ 7 
 
Schema ......................................................................................................................................... 8 
 
Schedule of Activities ................................................................................................................... 9 
2 
Introduction ..................................................................................................................... 10 
 
Study Rationale ........................................................................................................................... 10 
 
Background ................................................................................................................................. 11 
 
Pharmacological and non-pharmacological treatment of axial 
spondyloarthritis......................................................................................................................... 12 
 
Clinical assessment of axial spondyloarthritis ............................................................................ 12 
 
Follow-up strategies in axial spondyloarthritis ........................................................................... 13 
 
Benefit/Risk Assessment ............................................................................................................ 14 
 
Risk Assessment .......................................................................................................................... 14 
 
Benefit Assessment .................................................................................................................... 14 
 
Overall Benefit: Risk Conclusion ................................................................................................. 14 
 
Objectives and endpoints ........................................................................................................... 15 
3 
Study Design ..................................................................................................................... 16 
 
Overall Design ............................................................................................................................. 16 
 
Scientific Rationale for Study Design .......................................................................................... 16 
 
Conventional treatment target................................................................................................... 16 
 
Primary outcome measure ......................................................................................................... 17 
 
Intervention ................................................................................................................................ 17 
 
Participant Input into Design ...................................................................................................... 17 
 
End of Study Definition ............................................................................................................... 18 
4 
Study Population .............................................................................................................. 18 
 
Inclusion Criteria ......................................................................................................................... 18 
 
Exclusion Criteria ........................................................................................................................ 18 
 
Lifestyle Considerations.............................................................................................................. 19 
 
Screen Failures............................................................................................................................ 19 
5 
Study Intervention ............................................................................................................ 20 
 
Study intervention ...................................................................................................................... 20 
 
Medical treatment for all three arms ......................................................................................... 20 
 
Usual care arm ............................................................................................................................ 21 
 
Remote monitoring arm ............................................................................................................. 21 
 
Patient-initiated care arm........................................................................................................... 22 
 
Measures to Minimize Bias: Randomization and Blinding ......................................................... 23 
 
Study Intervention Compliance .................................................................................................. 23 
6 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal ............................................................................................. 25 
 
Discontinuation of Study Intervention ....................................................................................... 25 
 
Participant Discontinuation/Withdrawal from the Study .......................................................... 25 
 
Lost to Follow up ........................................................................................................................ 25 
7 
Study Assessments and Procedures ................................................................................... 26 
 
Study visits .................................................................................................................................. 26 

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Screening .................................................................................................................................... 26 
 
Assignment of intervention and subject numbering .................................................................. 26 
 
Baseline visit ............................................................................................................................... 27 
 
Regular visits ............................................................................................................................... 27 
 
Unscheduled visits ...................................................................................................................... 27 
 
End of study visit ......................................................................................................................... 28 
 
Withdrawal visit .......................................................................................................................... 28 
 
Efficacy assessments .................................................................................................................. 28 
 
Patient-reported outcome measures ......................................................................................... 28 
 
Clinical examination/assessment ............................................................................................... 29 
 
Laboratory assessment ............................................................................................................... 30 
 
Composite measures of disease activity .................................................................................... 30 
 
Safety assessments ..................................................................................................................... 30 
 
Physical Examinations ................................................................................................................. 30 
 
Vital signs .................................................................................................................................... 31 
 
Clinical Safety Laboratory Assessments (every 3rd month and all visits) .................................. 31 
 
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety 
Reporting .................................................................................................................................... 31 
 
Time Period and Frequency for Collecting AE and SAE Information .......................................... 31 
 
Method of Detecting AEs and SAEs ............................................................................................ 31 
 
Follow-up of AEs and SAEs.......................................................................................................... 31 
 
Regulatory Reporting Requirements for SAEs ............................................................................ 31 
 
Pregnancy ................................................................................................................................... 32 
 
Health Economics ....................................................................................................................... 32 
8 
Statistical Considerations .................................................................................................. 33 
 
Statistical Hypotheses ................................................................................................................ 33 
 
Sample Size Determination ........................................................................................................ 33 
 
Analysis Sets ............................................................................................................................... 33 
 
Statistical Analyses ..................................................................................................................... 34 
 
General Considerations .............................................................................................................. 34 
 
Primary Endpoint ........................................................................................................................ 34 
 
Secondary Endpoint .................................................................................................................... 35 
 
Safety Analysis ............................................................................................................................ 35 
9 
Supporting Documentation and Operational Considerations .............................................. 36 
 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ...................................... 36 
 
Regulatory and Ethical Considerations ....................................................................................... 36 
 
Informed Consent Process .......................................................................................................... 36 
 
Data Protection ........................................................................................................................... 36 
 
Dissemination of Clinical Study Data .......................................................................................... 37 
 
Data Quality Assurance .............................................................................................................. 37 
 
Source Documents ...................................................................................................................... 37 
 
Study and Site Start and Closure ................................................................................................ 38 
 
Publication Policy ........................................................................................................................ 38 
 
Appendix 2: Clinical Laboratory Tests ........................................................................................ 39 
 
Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................................ 40 
 
Definition of AE ........................................................................................................................... 40 
 
Definition of SAE ......................................................................................................................... 41 

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Recording and Follow-Up of AE and/or SAE ............................................................................... 41 
 
Appendix 5: ASAS Classification criteria for Axial Spondyloarthritis .......................................... 43 
 
Appendix 6: Patient-reported outcomes .................................................................................... 44 
 
Patient global assessment .......................................................................................................... 44 
 
Pain assessment.......................................................................................................................... 44 
 
 Joint pain assessment ................................................................................................................ 44 
 
Patient reported flare ................................................................................................................. 44 
 
BASDAI ........................................................................................................................................ 45 
 
BASFI ........................................................................................................................................... 46 
 
EQ-5D-5L ..................................................................................................................................... 47 
 
WPAI item no. 6 .......................................................................................................................... 49 
 
Patient-reported global change in disease activity .................................................................... 49 
 
Patient-reported global change in activity impairment ............................................................. 49 
 
Physical activity ........................................................................................................................... 50 
 
Patient satisfaction with care ..................................................................................................... 51 
 
Medication use ........................................................................................................................... 51 
 
Time use and costs related to consultations .............................................................................. 52 
 
Digital self-efficacy ...................................................................................................................... 53 
 
eHealth literacy ........................................................................................................................... 53 
 
Patient satisfaction with remote monitoring or patient-initated care ....................................... 54 
 
Appendix 8: Abbreviations and Definitions ................................................................................ 54 
10 
References........................................................................................................................ 56 
 
 
 
 

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1 Protocol Summary 
  Synopsis 
Study title 
Remote monitoring of axial spondyloarthritis in specialist healthcare services 
(ReMonit) 
Study Period 
 
Estimated date of first patient enrolled: September 7th 2021 
Anticipated recruitment period: September 7th 2021 - May 31st 2022 
Estimated date of last patient completed: November 30th 2023 
Intervention Duration/ 
Follow-up 
18 months 
Main objective 
To determine if two, new follow-up strategies for patients with axial 
spondyloarthritis (axSpA) are non-inferior in maintaining low disease activity 
over time compared to the conventional follow-up strategy with regular 
hospital visits. 
Main Inclusion Criteria    
 
Adult (>18 years of age) 
 
Clinical diagnosis of axSpA 
 
Fulfillment of diagnostic ASAS criteria for axSpA 
 
Stable medical treatment with tumour necrosis factor inhibitors (TNFi) 
the last 6 months 
 
Inactive or low disease activity (ASDAS<2.1) at inclusion 
Endpoints 
Primary endpoint:  
The point prevalence of low disease activity (defined as ASDAS <2.1) at the 6-, 
12- and 18-months follow-ups. 
 
Secondary endpoints:  
Individual and composite disease activity measures, patient global assessment 
of disease activity, general pain, joint pain, safety profile, adverse events, use 
of analgesics and antibiotics, health care resource use and societal costs 
related to consultations, health related quality of life, and patient satisfaction 
with care 
Number of patients 
240 patients (80+80+80) 
Study Design 
A single-site three-arm, parallel-group, non-inferiority follow-up strategy 
study, in which patient participants are randomized 1:1:1 to:  
 
a. Usual care: conventional follow-up strategy with pre-scheduled visits 
at the hospital every 6th month with a review of disease-related 
concerns, blood test results, joint examination, medication use, and 
adverse events 
or 
b. Remote monitoring: hospital health professionals (HPs) perform 
remote monitoring of frequent PROs and blood test results  
or 
c. Patient-initiated care: no pre-scheduled visits or remote monitoring 
 

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The treatment target, applicable to all arms, is that the patients consider their 
symptoms to be absent or mild and that their medication is effective. The 
patients in all three study arms are instructed to contact the hospital should 
they experience significant symptom worsening and consider that a 
consultation with HP is indicated. The HP will then evaluate and schedule a 
visit when needed. 
Intervention 
Two, new follow-up strategies will be implemented and evaluated: 
b) Remote monitoring: patients will self-report symptoms and register 
blood tests using an app on their smartphone or tablet. HPs will 
remotely monitor patient data and schedule a consultation when 
needed. 
c) Patient-initiated care: there will be no pre-scheduled visits or remote 
monitoring. This way more responsibility is placed on the patients to 
contact the hospital should they experience significant symptom 
worsening. When needed, the HP will schedule a consultation. 
Efficacy assessments 
 
Disease activity: Individual and composite disease activity measures at 
all three follow-ups 
 
Safety profile, adverse events, use of analgesics, prescribed antibiotics 
 
Patients’ satisfaction, pain, sleep, and health related quality of life 
 
Number of consultations in specialist or primary healthcare, costs and 
time for travelling, and time off work 
 
Work participation/sick leave 
Safety assessments 
Physical examination and vital signs, laboratory tests, record of adverse 
events and serious adverse events 
 
 Schema 
 

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  Schedule of Activities  
Procedure 
 
Screening 
 
Intervention Period [remote monitoring/visits] 
 
Baseline 
 
Every 
month 
6th month 
follow-up 
12th month 
follow-up 
18th month 
Study end 
Extra visits and 
 early discontinuation 
Inclusion and exclusion criteria  
X 
 
 
 
 
 
 
Fulfilment ASAS criteria1 
X 
 
 
 
 
 
 
Physical examination incl. heart and lungs 
X 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
Safety laboratory tests2 
 
X 
 
X 
X 
X 
X 
CRP and ESR 
 
X 
(X3) 
X 
X 
X 
X 
Clinical examination of disease activity, 
incl. enthesitis (heel), peripheral arthritis 
 
X 
 
X4 
X4 
X 
X 
Vital signs5 
 
X 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
Demography 
 
X 
 
 
 
 
 
Lifestyle 
 
X 
 
 
 
 
 
Patient global assessment 
 
X 
X6 
X 
X 
X 
X 
Patient-reported outcomes 
 
X 
X6 
X 
X 
X 
X 
Medication review 
 
X 
 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Adverse event review 
 
 
 
X 
X 
X 
X 
Reason for discontinuation7 
 
 
 
 
 
 
X 
1 The ASAS criteria include: Sacroilitis on imaging, HLA-B27 and SpA features (see 9.5.1) 
2 Patients using biologic medication, including the tumour necrosis factor inhibitors (TNFis), are instructed to take safety laboratory tests each 3rd month. For the “Usual care” 
arm, the patients will take blood tests at the 6th month visit at the hospital and take an additional blood test between these visits, which normally is prescribed and monitored by 
their general practitioner. For the “Remote monitoring” and “Patient-initiated care” arms, the patients are instructed to take blood tests each 3rd month, which normally is 
prescribed and monitored by their general practitioner. Patients, who normally take the 3-month blood tests at the hospital due to convenience, may continue this practice. 
Each 6th month the patients in the two latter arms will be requested to upload a photo of the blood test results into the MyDignio app. 
3 Only for the subgroup n=15 in the “Remote monitoring” arm that receive a home-based CRP instrument 
4 At 6 and 12 months only in the “Usual care” arm 
5 Pulse, blood pressure, body weight and height  
6 Patients in the “Remote monitoring” arm will complete a brief questionnaire each month, and patients in the “Patient-initiated care” only each 3rd month. Longer 
questionnaires will be completed by all study arms each 6th month. 
7 Only at “Early discontinuation” visit 
Abbreviations: CRP: C-Reactive Protein, ESR: Erythrocyte Sedimentation Rate, HLA-B27: Human Leucocyte Antigen B27  
 
 

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2 Introduction 
This protocol outlines an 18-months, non-inferiority randomized, controlled trial with three parallel 
arms to determine if two, new follow-up strategies for patients with axial spondyloarthritis (axSpA) are 
non-inferior in maintaining stable, low disease activity over time compared to the conventional follow-
up regimen with regular hospital visits. 
 Study Rationale 
The rapid development of technology and innovations for collecting patient-reported outcomes (PROs), 
remote patient monitoring, and medical decision support tools have opened an era for more 
personalized, and potentially better, treatment strategies for chronic diseases. Remote monitoring has 
shown consistent positive outcomes in chronic conditions like cardiovascular and respiratory disease1. It 
may also be effective for the management of inflammatory rheumatic diseases2,3, but remote 
monitoring has not yet been formally tested or utilized in the management of people with rheumatic 
diseases in Norway. These are serious, chronic diseases affecting the working age population with 
follow-up management taking place in specialist healthcare. Hence, utilizing remote monitoring to 
improve management of care can have beneficial effects for both individuals and the society. Recently, 
the Norwegian Directorate of Health, the Norwegian Directorate of eHealth and the Norwegian 
Medicines Agency delivered a report to the Ministry of Health and Care Services on how to facilitate 
implementation and dissemination of patient remote monitoring. Remote monitoring is a strategic 
priority in a recently published plan for the specialist healthcare services in Norway (“Nasjonal helse- og 
sykehusplan”) for achieving a sustainable healthcare sector4. 
 
The COVID-19 pandemic has resulted in a rapid implementation of digital technology in the healthcare 
sector in general. While adopting and implementing new innovations may have several beneficial 
effects, the research evidence on remote monitoring of patients with rheumatic diseases is very 
limited2,3. There is a need to determine whether remote monitoring for this patient group is equally 
effective in maintaining a stable, low disease activity as traditional outpatient visits at the hospital. The 
medical treatment of axSpA has been revolutionized during the last two decades, after the introduction 
of biologic medication, including the tumour necrosis factor inhibitors (TNFis). These drugs improve 

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symptoms and substantially inhibit inflammation in the majority of patients regardless of disease 
duration5,6. However, adherence to medication is only moderate over the long term7. Since non-optimal 
adherence compromises therapeutic efficacy and may lead to complications, unnecessary treatment 
switches and heightened costs, optimization of adherence should be integrated in new care models7,8. It 
is currently unknown if digital remote monitoring may increase, or decrease, adherence to medical 
treatment. 
 
In June 2020, a quality assurance study on video consultations at Division of Rheumatology and 
Research at Diakonhjemmet Hospital was conducted. This included an electronic patient survey (n=139) 
and focus group interviews (7 nurses, 7 rheumatologists). Both the patients and the health professionals 
(HPs) reported high satisfaction with video consultations and considered video consultation to be 
suitable for follow-up care, also in a non-pandemic situation. The study further revealed that axSpA 
would be the optimal patient group for testing remote monitoring since this is a predominantly young 
population with a large proportion reaching a low disease activity state. Furthermore, for axSpA, the 
prospects of potential joint damage in case of non-optimal treatment are much smaller compared to 
other rheumatic diseases, e.g., rheumatoid arthritis. 
 
In this randomized, controlled trial (RCT), we will compare two, new follow-up strategies for axSpA 
patients with conventional outpatient follow-up. The purpose is to investigate whether axSpA patients 
with stable, low disease activity and stable medication can be remotely monitored, i.e. be scheduled for 
consultations only when they experience significant symptoms worsening. We will further investigate 
whether regular monitoring by HPs is unnecessary and if patients and HPS are equally adept to judge 
when a hospital visit is needed. 
 
 Background 
AxSpA is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, but 
inflammation in peripheral joints and at the site of muscle/tendon attachment are also frequent9. The 
prevalence of axSpA is from 9 to 30 per 10 000 in the general population10. The main symptoms, back 
pain and stiffness, may lead to limited mobility of the spine, fatigue and functional disability. The 
evolution of axSpA is marked by alternated periods of flares (disease activity worsening) and stable 

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disease activity. Assessments of flares are needed for evaluations of disease status and treatment 
efficacy11. Uncontrolled, the disease may lead to structural damage, employment obstacles and serious 
socio-economic load12,13. Current treatment guidelines propose a treat-to-target strategy aiming at 
minimal or low disease activity14 and recommend a combination of pharmacological and non-
pharmacological treatment modalities15. 
 
Pharmacological and non-pharmacological treatment of axial spondyloarthritis 
 
Non-steroidal anti-inflammatory drugs (NSAIDs) and exercise represent the first line treatment of axial 
SpA, which often leads to reduced back-pain and stiffness. For patients with inadequate effects of 
NSAIDs and exercise, TNFis may be tested as the next step. TNFis improve symptoms and substantially 
inhibit inflammation in the majority of patients regardless of disease duration5,6. It is currently unknown 
if digital remote monitoring may increase, or decrease, adherence to medical treatment. 
 
Physical activity and exercise are important parts of the treatment regimen as most patients experience 
a relief of symptoms by exercise15. While several studies have demonstrated beneficial effects of 
exercise on disease activity16,17, high disease activity may also reduce the ability to be physically active 
due to pain, stiffness and fatigue18. A recent pilot study employing machine learning showed that 
episodes of reduced physical activity were associated with disease flares among patients with SpA and 
rheumatoid arthritis19. Thus, automatic monitoring may lead to early identification of flares20. This may 
pave the way for future remote monitoring of disease activity with great precision and minimal patient 
burden, but further testing is needed19. Compared to the general population, patients with axSpA have a 
higher risk of cardiovascular disease and cardiovascular mortality21. The increased risk is partly related to 
a higher prevalence of traditional risk factors22, but the systemic, chronic inflammation is recognized as 
an independent risk factor23. Physical activity and exercise can reduce this risk21.  
 
Clinical assessment of axial spondyloarthritis 
The disease course can be unpredictable, with periods of relatively lower disease activity interspersed 
with clinically significant worsening (disease flares) with up to 75% of patients reporting a current or 
past flare24. Ankylosing Spondylitis Disease Activity Score (ASDAS) is a common clinical measure of 
disease activity calculated from four PROs and C-reactive Protein (CRP). ASDAS <2.1 is regarded as an 
acceptable, low disease activity level25, and an increase of ASDAS>0.9 is considered a clinical important 

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worsening26. Patients can also self-report their “global assessment of disease activity” on a 0-10 or 0-100 
scale, and a flare has been defined as a relative change of ≥2 on a 0-10 scale11. 
 
Follow-up strategies in axial spondyloarthritis 
SpA care is resource demanding since it requires long-term treatment with regular monitoring and costly 
drug treatments. A recent study from UK showed that 93% of patients with axSpA were reviewed by a 
rheumatologist at least once a year, and 23% were reviewed three or more times a year27. In Norway, 
patients with axSpA on biologic medication have traditionally been followed by rheumatologists at the 
out-patient clinic with a 3-month interval in the beginning, and thereafter ideally every 6th month.  
 
Since the conventional outpatient follow-up regimen is scheduled using standardized time intervals and 
not based on the disease activity in the individual patient, the visit may not occur when it is needed the 
most (e.g., when severe flares or adverse effects occurs). In addition, for patients with axSpA with 
stable, low disease activity, several visits could likely be postponed. A study on outpatient visits among 
patients with rheumatoid arthritis showed that 30% of the visits led to no examinations or other actions, 
and 42% of visits were considered unnecessary by the rheumatologist28. 
 
A previous RCT showed that patients with rheumatoid arthritis and psoriasis arthritis were able to self-
monitor their blood tests and disease activity leading to a 50% reduction in hospital visits while 
maintaining acceptable disease activity and psychosocial well-being29. Patient interviews revealed that 
they described usual care as burdensome and inefficient use of time for those in employment, and that 
being able to self-monitor and initiate their own personalized care increased patient empowerment30. In 
Denmark a PRO–based remote monitoring follow-up strategy for tight control of disease activity was 
recently compared with conventional outpatient follow-up in an RCT among patients with rheumatoid 
arthritis. The Danish follow-up strategy with PROs every 3-4 months and a telephone call from a nurse or 
rheumatologist, achieved similar disease control as usual care follow-up; with less visits per year31 and a 
possible cost-saving impact32. 
 
 
 
 
 

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 Benefit/Risk Assessment 
 
Risk Assessment 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Missed detection of no 
efficacy of medical 
treatment or 
underreporting of 
symptoms 
(“Remote monitoring” and 
“Patient-initiated care” 
arms) 
In theory, less hospital visits may have 
negative effects like non-adherence to 
treatment, under-reporting of 
symptoms and that patients develop 
tolerance for high disease activity levels 
Frequent patient self-reporting in combination with 
patient-registered blood test results every 6th month 
should allow for detection of loss of efficacy, 
underreporting or increasing tolerance levels.  
Missed detection of 
clinically important side-
effects/adverse events 
(“Remote monitoring” and 
“Patient-initiated care” 
arms) 
If patients underreport or fail to 
complete the self-reporting or register 
blood test results, important side-effects 
or adverse events may not be detected 
Patients repeatedly failing to complete the self-
reports will be contacted. 
 
 
Benefit Assessment 
All participants may benefit from the frequent collection of self-reported outcomes, physical or digital 
visits and predefined treatment goals and therapy. Patients in the two, new follow-up arms may save 
time off from work and travel time as well as travel costs compared to standard care with hospital visits.  
 
Overall Benefit: Risk Conclusion 
For axSpA, the prospects of potential joint damage in case of non-optimal treatment are much smaller 
compared to other inflammatory rheumatic diseases, e.g., rheumatoid arthritis. Given the close 
monitoring in the remote monitoring group with frequently brief self-reporting of disease activity and 
symptoms as well as blood test results, we consider that a significant worsening of the disease activity is 
likely to be detected and that treatment to minimize the impact in patient outcomes will be initiated 
when needed. The patient-initiated care arm is instructed to contact the hospital if they experience 
symptoms worsening or adverse events. 
 
 
 

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Objectives and endpoints 
 
Objectives 
Endpoints  
Primary 
 
Assess if two, new follow-up strategies are non-inferior 
compared to conventional follow-up with hospital visits 
in terms of maintaining low disease activity 
Disease activity (ASDAS) at 6, 12 and 18 months 
Secondary 
 
Compare additional measures of clinical efficacy between 
the treatment arms 
Efficacy measures outlined in section 7.2 at each time 
point 
Compare the safety of the two, new follow-up strategies 
in axSpA with the conventional follow-up strategy 
Safety profile and adverse events throughout the 
study + doses of analgesics + prescribed antibiotics 
Assess if the patients and HPs are equally adept to judge 
the need for consultation 
Comparing the proportions that are scheduled for a 
visit when a serious disease activity worsening (flare) 
occurs  
 
Additional 
 
Evaluate cost effectiveness of remote monitoring in 
axSpA 
 
Health related quality of living, health care utilization 
and costs related to the societal perspective (e.g. work 
participation) as outlined in section 7.4. at each, or a 
combination, of time points.  
Examine fluctuations in disease activity and physical 
activity level over time 
Self-reported disease activity every month, blood tests 
every 6th month, and monthly CRP for a subgroup of 
participants. Physical activity data from wearing an 
activity tracker in the two, new follow-up strategy 
arms  
Examine if flares can be detected based on changes in 
monitored physical activity level 
Physical activity tracker data (steps per day and 
minutes with moderate and high intensity activity 
levels) and measures of disease activity 
Investigate barriers and facilitators for remote monitoring 
among HPs and patients 
Questionnaire at baseline among HPs and patients 
Investigate the HPs’ and patients’ perspectives and 
satisfaction with remote monitoring 
Semi-structured interviews of 10-15 patients and their 
treating rheumatologist and/or nurse 
Investigate HPs’ and patients’ experiences with video 
consultations, as compared to hospital visits and 
telephone consultations, and the impact of self-reporting 
on the follow-up care 
Semi-structured interviews and observations of 10-15 
patients and their treating rheumatologist and/or 
nurse 
Investigate the optimal frequency of collecting patient 
self-reported outcomes based on HPs’ experiences in 
clinical decision making, patients’ preferences, and 
disease activity fluctuation data 
Semi-structured interviews of 10-15 patients and their 
treating rheumatologist and/or nurse. Comparing 
observed fluctuations in diseases activity with the 
frequency of patient self-reporting 
 
 
 

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3 Study Design 
  Overall Design 
 
Randomised 
 
Single-blind  
 
Parallel group 
 
Non-inferiority 
 
Treatment strategy: conventional follow-up with hospital visits vs. remote monitoring vs 
patient-initiated care  
 
Study intervention assignment:  1:1:1 central computer randomisation  
 
Patients with axSpA > 18 years of age and low disease activity (ASDAS<2.1) 
 
Primary end point: the point prevalence of low disease activity at the 6-, 12- and 18-month 
follow-ups 
 
Duration of study: 18 months 
 
  Scientific Rationale for Study Design 
The study is designed to investigate if two, new follow-up strategies for patients with axSpA are non-
inferior to the conventional follow-up strategy with hospital visits for maintaining a stable, low disease 
activity. Hence, a randomized, controlled design is required to provide a valid comparison.  A non-
inferiority design is chosen as the two, new follow-up strategies are likely to be less resource-intensive, 
but they may still not be inferior compared to conventional follow-up for maintaining a stable, low 
disease activity.  Based on data from the NOR-DMARD database (ClinicalTrials.gov NCT01581294), 88% 
of the patients remained at a stable, low disease activity level (ASDAS >2.1) after two-year follow-up, 
hence, superiority may be difficult to achieve.  
 
Conventional treatment target  
The protocol adheres to current treatment recommendations to ensure appropriate care for patients 
and to ensure generalizability of results14,15. The goal of treating the patient with axSpA is to maximize 
long-term health-related quality of life through control of symptoms and inflammation, prevention of 
progressive structural damage, preservation/normalization of function and social participation15. This 
implies that the patients consider that their symptoms are absent or mild and that their medication is 
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Primary outcome measure 
The primary outcome for this trial is the point prevalence of low disease activity (defined as ASDAS< 2.1) 
at the 6-, 12- and 18-monts follow-ups.  
Ankylosing Spondylitis Disease Activity Score (ASDAS) is a common clinical measure of disease activity 
calculated from four PROs and CRP (or ESR if CRP is not available). The formula for calculating ASDASCRP 
= 0.12 × back pain + 0.06 × duration of morning stiffness + 0.11 × patient global + 0.07 × peripheral 
pain/swelling + 0.58×Ln(CRP + 1)). The formula for calculating ASDASESR = 0.08 x back pain + 0.07 x 
duration of morning stiffness + 0.11 x patient global + 0.09 x peripheral pain/swelling + 0.29 x √(ESR).  
There is a defined cut-off for low disease activity which allows using the ASDAS score as a target, and 
ASDAS <2.1 is regarded as an acceptable, low disease activity level25. ASDAS is also a continuous 
measure, which makes it appropriate to assess potential changes in disease activity, and an increase of 
ASDAS>0.9 is considered a clinical important worsening26. 
 
Intervention 
The remote monitoring study arm includes implementing remote monitoring and remote care using the 
Dignio platform and software allowing for remote collection of PROs, patient monitoring and triaging by 
using the clinicians’ dashboard and asynchronous chat, as outlined in 5.1.3 and 5.1.4.  
The patients in the “Patient-initiated care” arm will have no remote monitoring and no pre-scheduled 
hospital visits but will be instructed to contact the hospital should they experience significant symptom 
worsening and consider that a consultation with a health professional is indicated. 
In a substudy, the patients in the two intervention arms will be asked to wear wrist bands/smart 
watches during daytime for physical activity tracking, but this data will not be monitored and will only be 
collected for the purpose of research. A subgroup of 10-15 participants will use a CRP instrument for 
home-based measurements. 
 
Participant Input into Design 
Patient research partners, Tale Gjøvik and Sarah Hakim, are included in the project group. They have 
provided input on the relevance of the research question, the feasibility of the study design from a 
patient perspective and written information to patients. They will continue their involvement for the 
continuation of the study.  

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 End of Study Definition 
A participant is considered to have completed the study if he/she has completed all phases of the study 
including the last visit. The study period is 18 months, with a possible extension to 36 months, which will 
be decided by the study project group. The end of the study is defined as the date of the last visit of the 
last participant in the study.  
 
4 Study Population 
 Inclusion Criteria 
Participants are eligible to be included in the study only if all the following criteria apply: 
 
Male or female >18 years of age at screening 
 
Patients with a diagnosis of axSpA who fulfil the diagnostic ASAS criteria for axSpA (see Appendix 9.4) 
 
Stable medical treatment with TNFi the last 6 months 
 
Inactive or low disease activity (ASDAS<2.1) at inclusion 
 
Capable of understanding the Norwegian language and of signing an informed consent form 
 
 Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions: 
 
Major co-morbidities, such as severe malignancies, severe diabetes mellitus, severe infections, 
uncontrollable hypertension, severe cardiovascular disease (NYHA class III or IV), severe 
respiratory diseases, and/or cirrhosis. 
 
Indications of active tuberculosis (TB) 
 
Pregnant or nursing 
 
Diagnostic assessments: 
 
Abnormal renal function, defined as serum creatinine >142 µmol/L in female and >168 µmol/L in 
male, or glomerular filtration rate (GFR) <40 mL/min/1.73 m2 
 
Abnormal liver function (defined as Alanine Transaminase (ALT) >3x upper normal limit), active or 
recent hepatitis 
 
Leukopenia and/or thrombocytopenia 
 

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Other:  
 
Severe psychiatric or mental disorders, alcohol abuse or other substance abuse, language 
barriers or other factors which makes adherence to the study protocol impossible 
 
 Lifestyle Considerations 
Female patients planning pregnancy within the study period will not be recruited as this will induce a 
different follow-up pattern not compatible with this study design. No lifestyle changes are otherwise 
required for participation in the study.  
 Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are not 
subsequently randomly assigned to study intervention. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries from 
regulatory authorities. Minimal information includes demography, screen failure details, eligibility 
criteria, and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened.  
 

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5 Study Intervention 
 Study intervention 
The ReMonit study is a randomized, controlled study with three parallel arms, and the design is 
illustrated in Figure 1. AxSpA patients are randomized 1:1:1 to either:  
a. Usual care: conventional follow-up strategy with pre-scheduled visits at the hospital every 6th 
month with a review of disease-related concerns, blood test results, joint examination, 
medication use, and adverse events 
or 
b. Remote monitoring: hospital health professionals (HPs) perform remote monitoring of frequent 
PROs and blood test results   
or 
c. Patient-initiated care: no pre-scheduled visits or remote monitoring 
 
Figure 1: Illustration of the ReMonit study design.  
 
 
 
Medical treatment for all three arms 
The medical treatment will be the same for all three study arms and will follow the current treatment 
recommendations for axSpA15. At inclusion, all patients will have low disease activity. The treatment target 
for all three study arms is that the patients consider their symptoms to be absent or mild and that their 
medication is effective. The treatment will be individualized by the treating physician according to signs 

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and symptoms of the disease and patient characteristics. If TNFi therapy fails, switching to another TNFi 
alternative or an anti-IL-17 therapy may be considered. 
 
All included patients will be on stable medical treatment with TNFi for the last 6 months. Patients will be 
instructed to use NSAIDs should they experience minor worsening of symptoms, but if the patients 
experience significant symptom worsening and suspect a severe disease worsening (flare) or adverse 
events, they will be instructed contact the hospital (Table 1). A visit will be arranged within two weeks to 
allow for examination and documentation of disease status. Concomitant medication will be recorded in 
the CRF, with particular attention to registration of use of NSAIDs, oral or injected glucocorticoid, and 
analgesics for residual pain (paracetamol or opioids).  
 
Patients in all three study arms will be instructed to take blood tests for assessment of safety and side 
effects each 3rd month as prescribed and monitored by their general practitioner. Patients, who normally 
take these 3-month blood tests at the hospital due to convenience, may continue this practice. 
 
Usual care arm 
Patients in the “Usual care” arm will be treated according to current conventional follow-up regimen 
with regular hospital visits. In the ReMonit study this includes prescheduled face-to-face visits with an 
experienced rheumatology nurse at 6 and 12 months and with a rheumatologist at 18 months (study 
end), with a review of disease-related concerns, blood test results, joint examination as well as 
recording medication use, and adverse events. 
 
Remote monitoring arm 
The patients in this study arm will download the app, MyDignio, on their smartphone or tablet and 
receive a brief introduction on the use of MyDignio from the study coordinator. MyDignio app will be 
used for reporting PROs, displaying results (histograms) for PROs over time, and for asynchronous (chat) 
communication with HPs. The patients will receive a SMS reminder for “tasks” (e.g., self-reporting PROs 
or uploading a photo with blood test results each 6th month) according to the planned time points as 
outlined in 7.2- 7.3. The patients will receive an automatic reminder when a task is uncompleted.  
A subgroup of patients (n= 10-15) will use a CPR instrument for home-based monthly self-
measurements of CRP. The patients will register the CRP value in the MyDignio app. 

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The patients will be asked to wear a wrist band/smart watch for physical activity monitoring over 12 
months. They will be instructed to wear this activity tracker at least 10 hours during daytime, but they 
can wear the water-resistant tracker all day and night should they want to. The number of steps and 
mean pulse levels will be collected per minute for research purposes.  
A study coordinator/nurse will once daily (Monday to Friday) log on to the digital platform, Dignio 
Prevent, to monitor the PROs and respond to potential patient messages/questions. By setting 
acceptable maximum and minimum values for the outcomes (see table 2), a triaging functionality in the 
Dignio Prevent software will aid the study coordinator/nurse in highlighting PROs or measurements that 
needs attention. The software will also indicate if the patient misses one or more self-reports or 
measurement registrations. 
The patients can send a message to the HP through the app, and HPs can reply or call the patient to 
investigate if there is a need to schedule a visit. The software uses a standardized application program 
interface, and all communication through the software is encrypted and in compliance with current 
legislation.  
 
Patient-initiated care arm 
Patients in this arm will also download the app, MyDignio, on their smartphone or tablet and receive a 
brief introduction from the study coordinator. The app will be used to collect PROs. Patients are 
instructed to contact the hospital if they need an evaluation regarding medication, symptoms worsening 
or adverse events. The patients will receive a SMS reminder for “tasks” (e.g. self-reporting or uploading 
a photo with blood test results each 6 months) according to the planned time points as outlined in 7.2- 
7.3. The patients will receive an automatic reminder if the task is not completed. 
 
 

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Table 1: Indication for unscheduled/extra visits for all three study arms 
Indication 
Definition 
Action 
Significant 
worsening 
Patient-reported significant symptoms 
worsening 
The HP excludes other potential reasons for the 
experienced worsening. If there is a need for 
changing medication, a physical examination or 
blood test, a visit will be scheduled within two 
weeks 
Significant 
adverse effects 
Safety laboratory test results showing 
adverse effects or patient-reported 
adverse events 
Schedule a visit within two weeks 
 
Table 2: Indication for the HPs to contact a patient in the Remote monitoring study arm 
Indication 
Definition 
Action 
Significant 
worsening 
Yellow flag: BASDAI ≥4 in the monthly 
PRO reporting 
 
Red flag: BASDAI ≥8 in the monthly PRO 
reporting 
The study nurse contacts the patient to 
evaluate if a hospital visit is needed  
The patient has 
requested to be 
contacted by HP 
The patient sends a message in 
MyDignio app asking to be contacted by 
HP 
The study nurse contacts the patient to 
evaluate if a hospital visit is needed 
1 PGA: Patient Global Assessment of disease activity 
 
 
 Measures to Minimize Bias: Randomization and Blinding 
Eligible patients will be allocated in a 1:1:1 ratio between the three study arms. A statistician and a 
secretary, not involved in patient screening or enrollment, will provide a computer-generated block 
randomization list, and prepare sealed, opaque envelopes containing information on study arm 
assignment. Details of block size and allocation sequence generation will be provided in a separate 
document unavailable to those who enroll patients or assign treatment.  The study does not include 
blinding of participant and treating health care personnel.  
 
 Study Intervention Compliance 
Compliance to treatment will be assessed as the proportion of completed self-reports at all time points 
for self-reporting and the proportion who register their blood test results at 6- and 12-months. Full 

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compliance is defined as completion of ≥80% of all frequent self-reports and 100% of all half-year self-
reports and blood test results. Partial compliance is less than full, but ≥60% completed frequent self-
reports, and 2 half-year self-report and blood test result registered. Low compliance is <60% completed 
frequent self-reports, and only 1 half-year self-report and 1 blood test result registered.   
Full compliance to medical treatment is defined as taking the treatment as prescribed, partial 
compliance is less than 100% but more than 70% compliant to prescribed treatment, and low 
compliance is less than 70% compliant.  Reason for non-compliance (lack of efficacy/adverse 
events/concurrent medical condition/patient wish/other) will be assessed.   
 
 

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6 Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal 
 Discontinuation of Study Intervention 
Patients who for some reason withdraw from following the treatment protocol will be asked to continue 
follow-up in the study. 
 Participant Discontinuation/Withdrawal from the Study 
Patients have the right to withdraw from the study at any time for any reason. In the case that a patient 
decides to prematurely withdraw from the study, he or she should be asked if they can still be contacted 
for further information, so that a final evaluation can be made with an explanation of why the patient is 
withdrawing from the study, including assessment of possible adverse events.  Although a subject is not 
obliged to give his or her reason(s) for withdrawing prematurely from a trial, the investigator should 
make a reasonable effort to ascertain the reason(s), while fully respecting the subject's rights. If 
possible, at the last visit of the patient all assessments of the” Early discontinuation of study visit” will be 
done. 
 Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits or to complete self-reports and is unable to be contacted by the study site. If a participant in the 
“Usual care” arm fails to return to the clinic for a required study visit, the study coordinator must 
attempt to contact the participant and reschedule the missed visit as soon as possible and counsel the 
participant on the importance of maintaining the assigned visit schedule and ascertain whether the 
participant wishes to and/or should continue in the study. If a participant in any of the two, new follow-
up strategy arms fail to report the half-year self-reports and register blood test results, the study 
coordinator must attempt to contact the participant and counsel the participant on the importance of 
maintaining the self-report schedule and ascertain whether the participant wishes to and/or should 
continue in the study. Before a participant is deemed lost to follow up, the coordinator must make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods). These 

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contact attempts should be documented in the participant’s medical record. Should the participant 
continue to be unreachable, he/she will be considered to have withdrawn from the study.  
 
 
7 Study Assessments and Procedures 
Study procedures and their timing are summarized in the Schedule of Activities. Adherence to the study 
design requirements, including those specified in the Schedule of Activities, is essential and required for 
study conduct. 
 Study visits 
 
Screening 
All screening evaluations as outlined in the Schedule of Activities must be completed and reviewed to 
confirm that potential participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record reasons for screening 
failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management and obtained before 
signing of the informed consent form may be used for screening purposes provided the procedures met 
the protocol-specified criteria and were performed within the time frame defined in the Schedule of 
Activities. Laboratory measures preformed < 14 days prior to screening can be used.  
 
Assignment of intervention and subject numbering 
Eligible patients will be assigned a unique patient identification number. Once assigned, this number 
cannot be reused for another patient. The patients will be randomized 1:1:1 to the three arms as 
described in section 5.1. 
 
 

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Baseline visit 
At the baseline visit all assessments outlined in 7.2. and 7.3 except AE/SAE will be assessed. In addition, 
the following data will be recorded: 
o Demography: age, sex, education, work status 
o General medical history: previous and current comorbidities and previous and current 
medications 
o Disease specific medical history: symptom duration, date of diagnosis, current and previous SpA-
features (peripheral arthritis, enthesitis), SpA associated disease (uveitis, psoriasis, inflammatory 
bowel disease), family history of SpA and SpA associated diseases. 
o Fulfilment of ASAS criteria including HLA B27, X-ray and/or MRI findings on sacroiliac (SI) joints 
and spine as documented in the patient journal 
o Lifestyle factors: tobacco use and physical activity last seven days (frequency, intensity, and 
duration) 
o Patient satisfaction with care 
o Self-efficacy/confidence related to using smartphone, tablet, computer, app’s, secure login and 
digital health serviced: 6 items with response categories: Never used, Very bad, Bad, Neither 
good nor bad, Good, Very good  
o eHealth literacy (20 items from 4 domains from the eHealth Literacy Questionnaire (eHLQ) 33: 1) 
using technology to process health information, 2) ability to actively engage with digital services, 
3) feel safe and in control, 4) motivated to engage with digital services. Response options range 
from 1 (strongly disagree) to 4 (strongly agree). 
 
Regular visits 
Assessments are as outlined in the Schedule of Activities and in section 7.2.  
 
Unscheduled visits 
HPs can freely schedule additional visits as required according to clinical judgement. If patients in any of 
the three study arms suspects a disease worsening or AE, he or she should contact the hospital and be 
seen there within two weeks as the latest. Unscheduled visit will, if possible, include all assessments of a 
regular visit.  
 

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End of study visit 
The end of the study visit will be performed at 18 months and will include a formal end of study 
assignment in the eCRF. The patients will self-report their satisfaction with care. 
 
Withdrawal visit 
A withdrawal visit (early discontinuation) will include all assessments of a regular visit in addition to an 
assessment of reason for withdrawal and time of withdrawal. 
  Efficacy assessments  
 
Patient-reported outcome measures 
At Baseline (after screening, but before the randomization), patient demographics and PROs be 
collected using a digital device at the hospital.  
Every 6. month, patients will receive a link a digital survey (“Nettskjema” (Services for sensitive data 
(TSD), University of Oslo)). Collection of a few PROs from patients will be done monthly for the Remote 
monitoring arm and every third month for the Patient-initated care arm using the MyDignio app. The 
participants in these two intervention arm will also report blood test results every 6. month using the 
MyDignio app. 
• 
Patient global assessment of disease activity (PGA) (Visual Analogue Scale, NRS 0-10) (All arms: 
Baseline, 6-, 12- and 18-months) (Remote monitoring arm: each month) (Patient-initiated care arm: 
each 3rd month) 
• 
Patient-reported flares (All arms: 6-, 12- and 18-months) (Remote monitoring arm: each month) 
(Patient-initiated care arm: each 3rd month) 
If the patient responds “yes” or “uncertain” to the question if they have experienced a significant 
worsening of symptoms (reflecting a flare in disease activity), they will be asked which date the flare 
occurred and the number of days it lasted. 
• 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (All arms: Baseline, 6-, 12- and 18-
months) (Remote monitoring arm: each month if disease worsening) (Patient-initiated care arm: 
each 3rd month if disease worsening) 
BASDAI is a 6 item questionnaire (NRS 0-10) used to assess disease activity in ankylosing 
spondylitis34. The score is the sum (of the first four individual questions and the mean of questions 
five and six) divided by five.  
 
Bath Ankylosing Spondylitis Functional Index (BASFI) (Baseline) 
BASFI is a 10 item questionnaire (NRS 0-10)  used to assess disease activity in ankylosing 
spondylitis34. The score is the sum of each individual question divided by 10.  
 
Patient-reported pain (general) Single item (NRS 0-10) (Baseline, 6-, 12- and 18-months)  

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 
Patient-reported joint pain Single item (NRS 0-10) (Baseline, 6-, 12- and 18-months)  
 
Patient-reported global change in disease activity. Single item with seven-point response scale 
ranging from "Much worse" to "Much better” (6-, 12- and 18-months) 
 
Patient-reported global change in activity impairment. Single item with seven-point response scale 
ranging from "Much worse" to "Much better” (6-, 12- and 18-months) 
 
Euro Quality of Life 5 Dimensions 5 Levels (EQ5D-5L) (Baseline, 6-, 12- and 18-months) 
EQ-5D is a utility instrument for measurement of health related quality of life35 and is applicable to a 
wide range of health conditions and treatments, it provides a simple descriptive profile and a single 
index value for health status. 
 
Work Productivity and Activity Impairment (WPAI) – item no. 6 on activity Impairment (NRS 0-10) 
(Baseline, 6-, 12- and 18-months).  
 
Questions on physical activity from the HUNT study (Baseline, 6-, 12- and 18-months) The HUNT 
questionnaire consists of 3 questions assessing frequency, intensity, and duration of physical activity 
in the past 7 days 36. 
• 
Sleep disturbance (Baseline, 6-, 12- and 18-months) 1 item from the Pittsburgh Sleep Quality Index 
measuring sleep disturbance due to pain with four-point response categories ranging from "Not 
during the past month" to "Three or more times a week"37. 
• 
Patient satisfaction with care (Baseline, 6-, 12- and 18-months) 
Satisfaction with the care provided (from patient experience questionnaires) includes one item with 
five point response options ranging from “Very satisfied” to “Very dissatisfied” 38. 
 
Medication use (Baseline, 6-, 12- and 18-months) 
Questions on whether the patient has taken the TNFi medication as instructed, and if NSAIDs, 
glucocorticoid (oral or injections) or analgesics have been used. 
 
Time and costs related to consultations (Baseline) 
The time being absent from work and potential travel costs related to consultations will be 
registered. 
 
Clinical examination/assessment 
Clinical assessments will be performed as outlined for each element below. If possible, assessments of 
individual patients will be performed by the same assessor. Training in clinical examination will be 
provided for all assessors 
 
General clinical examination (baseline visit) 
 
Heel enthesitis and peripheral arthritis assessment (all visits) 
Assessment of heel enthesitis is done by palpating with sufficient pressure to blanch the anterior part of 
the examiner’s fingernail and scored as yes/no. For assessment of peripheral arthritis, the following 
joints are examined for tenderness and swelling: proximal interphalangial joints (1-5, 
metacarpophalangial joints (1-5), wrists, elbows, shoulders, knees, ankles, metatarsophalangial joints. 
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Laboratory assessment 
Assessment of inflammatory markers will be performed prior to each hospital visit by the hospital 
laboratory and includes ESR (mm/hr) and CRP (mg/L). All patients will be instructed to take standard 
care blood samples (hemoglobin, red blood cells, white blood cells with differential count, platelets, 
creatinine, and alanine transaminase) as a safety procedure when using TNFi as prescribed and 
monitored by their general practitioner. Patients, who normally take these blood tests at the hospital 
due to convenience, may continue this practice. Patients in the “Remote monitoring” and the “Patient-
initiated care” arms are instructed to report blood test results each 6th month in the MyDignio app. 
These blood tests will in addition be used to assess clinical safety (see 7.3.3). A small subgroup in the 
Remote monitoring group will receive a CRP-instrument and be asked to measure their CRP monthly and 
register the value in the MyDignio app. 
 
Composite measures of disease activity 
 
Ankylosing Spondylitis Disease Activity Score (ASDAS) (Baseline, 6-, 12- and 18-months) 
The ASDAS score is a 6-item composite measure of 4 PROs and CRP or ESR: 
ASDASCRP: 0.12 x back pain + 0.06 x duration of morning stiffness + 0.11 x patient global + 0.07 x 
peripheral pain/swelling + 0.58 x Ln(CRP+1).  
ASDASESR:  0.08 x back pain + 0.07 x duration of morning stiffness + 0.11 x patient global + 0.09 x 
peripheral pain/swelling + 0.29 x √(ESR). 
ASDASCRP is preferred, but the ASDASESR can be used in case CRP data are not available. CRP in mg/L; 
all patient assessments on a 10 cm scale. ASDAS <2.1 is regarded as an acceptable, low disease 
activity level25. ASDAS is also a continuous measure, which makes it appropriate to assess potential 
changes in disease activity, and an increase of ASDAS>0.9 is considered a clinical important 
worsening26.   
 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (Baseline, 6-, 12- and 18-months) 
BASDAI is a 6 item questionnaire (NRS 0-10) used to assess disease activity in ankylosing 
spondylitis34. The score is the sum (of the first four individual questions and the mean of questions 
five and six) divided by five.  
 
 Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities. 
 
Physical Examinations 
 
General clinical examination (baseline visit) 

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Vital signs 
 
Pulse and blood pressure (baseline visit) 
 
Height and weight (baseline visit) 
 
Clinical Safety Laboratory Assessments (every 3rd month and all visits) 
 
Haemoglobin, red blood cells, white blood cells with differential count and platelet count 
 
Glomerular filtration rate (GFR) and creatinin 
 
Alanine transaminase (ALT)  
 
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Reporting 
The definitions of adverse events (AEs) and serious adverse events (SAEs) as well as the method of 
recording, evaluating, and assessing causality of AEs and SAEs and the procedures for completing and 
transmitting SAE reports are provided in Appendix 3. 
 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the start of intervention until the final follow-up visit at the time 
points specified in Schedule of Activities. Medical occurrences that begin before the start of study 
intervention, but after obtaining informed consent, will be recorded as Medical History/Current Medical 
Conditions, not as AEs. All SAEs, including updates, will be recorded and reported to the sponsor or 
designee immediately, as indicated in Appendix 3. Investigators are not obligated to actively seek 
information on AEs or SAEs after conclusion of the study participation.  
 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about AE occurrences. 
 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant at 
subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is otherwise 
explained, or the participant is lost to follow-up.  
 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal obligations and 
ethical responsibilities are met. The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention under clinical 

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investigation. The sponsor will comply with regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Board and Independent Ethics Committee. 
 
Pregnancy 
Details of all pregnancies in female participants will be collected after the start of study intervention and 
until end of the study. If a pregnancy is reported, the investigator will record pregnancy information on 
the appropriate form and submit it to the sponsor. While pregnancy itself is not considered to be an AE 
or SAE, any pregnancy complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. Abnormal pregnancy outcomes are considered SAEs and will be reported as 
such. The participant will be followed to determine the outcome of the pregnancy and any post-study 
pregnancy-related SAE considered reasonably related to the study intervention by the investigator will 
be reported to the sponsor. Further participation in the study will be determined by the treating 
physician and principal investigator. 
 
 Health Economics  
Use of health care (costs) will be captured by the following registers: The Norwegian Patient Register 
(hospital services), The Norwegian Prescription Register (pharmaceuticals), Norway Control and Payment 
of Health Reimbursement - KUHR database (primary care services), Statistics Norway’s database on social 
benefits (FD Trygd). We will assign unit costs to each type of service by means of the diagnosis-related 
group (DRG) pricing system, and the price list of the Norwegian Medicines Agency. The patients will be 
asked about costs related to consultations, e.g., transport costs, time use, work absenteeism, need for 
support. We will also register the time study coordinator/nurse and rheumatologist spend on remote 
monitoring, telephone calls, replies to patient messages on the Dignio platform and similar. For each 
patient we will estimate one-year costs based on register data for utilization of health care and the unit 
costs. The mean quality adjusted life years (QALYs) and costs in the three arms will be used to estimate 
an incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB).  

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8 Statistical Considerations 
 Statistical Hypotheses 
Statistical hypothesis (non-inferiority test): 
Null hypothesis: The point prevalence of low disease activity (ASDAS<2.1) in both “Remote monitoring” 
and “Patient-initiated care” is more than 15 percentage points lower than in “Usual care” arm at any 
follow-up time point. 
Alternative hypothesis: The point prevalence of low disease activity (ASDAS<2.1) in “Remote 
monitoring” / “Patient-initiated care” is at most 15 percentage points lower than in “Usual care” arm at 
any follow-up time point. 
  Sample Size Determination 
Randomly assigning 80 participants to each of the three study arms will give approximately 80% power 
to conclude that at least one of the alternative follow-up strategies is non-inferior to conventional 
follow-up, using a 15% non-inferiority margin. This controls for multiple testing at the 5% level and 
assumes an analysis based on a logistic mixed model. We will additionally test the non-inferiority of 
“Patient-initiated care” to “Remote monitoring” using the same 15% margin. This test will be done only 
if “Patient-initiated care” is shown to be non-inferior to conventional care (a hierarchical test), and thus 
will not inflate the 5% false positive rate. 
 Analysis Sets 
Population 
Description 
Enrolled 
The Enrolled set will include all patients who have provided informed consent 
and have been included into the study data base. 
Intention to Treat Set 
The Intention to Treat (ITT) Set will include all patients randomly assigned to 
a study arm irrespective of post randomization occurrences. 
Full Analysis Set 
The Full Analysis Set (FAS) will be defined as all patients randomly assigned to 
a study arm and that have started the allocated intervention defined as 
having completed at least one assessment of the primary endpoint at 6, 12 or 
18 months. The FAS will form the primary analysis set of the study and will be 
used for primary non-inferiority analyses. 
Completer Analysis Set 
The Completer Analysis Set will include all randomized patients having 
started the allocated intervention and not withdrawn during the study.  
Per Protocol Analysis Set 
The Per Protocol Analysis Set (PPS) will include all randomized patients 
meeting the study entry criteria who followed the study protocol with no 
major protocol deviations.  

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  Statistical Analyses 
The statistical analysis plan (SAP) will be finalized prior to un-blinding and it will include a more technical 
and detailed description of the statistical analyses described in this section. This section is a summary of 
the planned statistical analyses of the most important endpoints including primary and key secondary 
endpoints. 
 
General Considerations 
 
Efficacy (both primary and secondary endpoints) and safety analyses will include data from all 
randomised patients who started the allocated intervention by attending at least one completed 
questionnaire and blood test result after randomisation (FAS), and robustness analyses will be 
performed in the PPS. 
 
Demographics, baseline characteristics, efficacy and safety variables will be summarised using 
descriptive statistics. 
 
All efficacy analyses will be presented with the results from the hypothesis testing (by p-value) 
in addition to estimates and 95% confidence limits of the treatment effect. For the primary 
variables specifically, this will be the estimated mean probability with corresponding 95% 
confidence limits.   
 
Primary Endpoint 
The primary endpoint is defined as the point prevalence of with low disease activity (defined as ASDAS 
<2.1) at the 6-, 12- and 18-months follow-ups.  
 
The probability of being in low disease activity for repeated measures per individual will be used to 
estimate a risk difference across the three study arms. The primary variables will be analyzed using 
logistic regression mixed models with allocated study arm as primary explanatory variable. Other pre-
specified covariates included in sensitivity analyses include age, gender, disease features. The SAP will 
detail these procedures, as well as alternative and further supportive evaluations, such as analyses 
including unbalanced baseline predictors or modifications of the regression model in case validity 
assumptions are not met. The primary analysis will be performed in the FAS. The primary endpoint will 
be evaluated by the p-value and confidence interval of the hypothesis test from the regression analysis. 

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In case the null hypothesis is not rejected, the new, follow-up strategies will be considered worse or 
inferior to usual care with hospital follow-up visits. 
 
Secondary Endpoint 
Between-group comparisons will be performed for secondary efficacy endpoints.  
The between-group comparisons for secondary endpoints will be tested as for the primary endpoint 
where applicable and additional analyses will be performed based on the following methods (but not 
limited to): 
 
Continuous secondary variables will be subject to repeated measures mixed models or appropriate 
non-parametric alternatives 
 
Binary response variables will be analyzed using logistic regression (possibly adjusting for within-
subject dependencies by mixed model approaches) or other appropriate tests, e.g., chi-
square/Mantel-Haenszel test 
Unless otherwise specified, all statistical hypotheses will be tested as the primary endpoint, i.e., with an 
assessment of non-inferiority based on the p-value of the group differences.  
 
Safety Analysis 
Rates and type of adverse events and serious adverse events in all three study arms will be reported. 
 
 

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9 Supporting Documentation and Operational Considerations 
 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the Consensus ethical principles 
derived from international guidelines including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, ICH Good Clinical Practice 
(GCP) Guidelines and applicable laws and regulation.  
The protocol, protocol amendments, informed consent form and Investigator Brochure must be 
reviewed and approved to the institutional review board and independent ethics committee before the 
study is initiated. Any amendments to the protocol will require approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate hazard to 
study participants.  
The investigator will be responsible for providing written summaries of the status of the study to the 
relevant authorities in accordance with their requirements and notify them of any significant safety 
findings. The investigator is also responsible for providing oversight of the conduct of the study at the 
site and adherence to relevant regulations.  
 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the study to the participant and 
answer all questions regarding the study. Participants must be informed that their participation is 
voluntary. Participants will be required to sign a statement of informed consent that meets the 
requirements of local regulations. Participants must be re-consented to the most current version of the 
informed consent form during their participation in the study and a copy must be provided to the 
participant. 
 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. The participant must be informed that 
his/her personal study-related data will be used by the sponsor in accordance with local data protection 
law. The level of disclosure must also be explained to the participant who will be required to give 

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consent for their data to be used as described in the informed consent. The participant must be 
informed that his/her medical records may be examined by auditors or other authorized personnel 
appointed by the sponsor, institutional review board, independent ethics committee or regulatory 
authorities. 
 
Dissemination of Clinical Study Data 
Study design and results will be registered at the US National Institutes of Health’s website 
www.clinicaltrials.gov. Trial results will be disseminated through non-promotional, peer-reviewed 
publications. Access to analyzable datasets from the clinical study can be granted through a secure 
system, following an independent assessment of the scientific merit of a rigorously defined research 
question from a third party. 
 
Data Quality Assurance 
All participant data relating to the study will be recorded on electronic case report file (eCRF). The 
investigator is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. Guidance on completion of CRFs will be provided in investigator brochure 
and eCRF. The investigator must permit study-related monitoring and regulatory reviews, audits and 
inspections. The investigator must provide direct access to source data documents. Monitoring details 
are provided in the monitoring plan and contracts. The sponsor or designee is responsible for the data 
management of this study including quality checking of the data and the sponsor assumes accountability 
for actions delegated to other individuals. Records and documents, including signed informed consent 
forms, pertaining to the conduct of this study must be retained by the investigator for 15 years after 
study completion. No records may be destroyed or transferred to another location or party during the 
retention period without the written approval of the sponsor.  
 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the integrity of 
the data collected. Source documents are filed at the investigator’s site. Data entered in the eCRF that 
are transcribed from source documents must be consistent with the source documents or the 
discrepancies must be explained. Definition of what constitutes source data can be found in the 
investigator brochure. Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and verifiable from source 

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documents; that the safety and rights of participants are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and all applicable regulatory 
requirements. 
 
Study and Site Start and Closure 
Study start 
The study start date is the date on which the clinical study will be open for recruitment of participants. 
 
Study Termination 
The sponsor or designee reserves the right to terminate the study at any time for any reason at the sole 
discretion of the sponsor. Reasons for the early closure of a study by the sponsor or investigator may 
include but are not limited to: Failure of the investigator to comply with the protocol, the requirements 
of the institutional review board, independent ethics committee or local health authorities, the 
sponsor's procedures, or GCP guidelines, inadequate or no recruitment or total number of participants 
included earlier than expected. 
 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, independent ethics committee and institutional review board and the regulatory 
authorities of the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 
 
Publication Policy 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
 
 

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 Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 6 will be performed at the hospital laboratory for any hospital visit including 
the standardized preplanned 6. month visits for the “Usual care” arm, unscheduled visits, early 
discontinuation visits and at study end visit. Patients will be instructed to take blood tests each 3rd 
month. The patient’s general practitioner will be responsible for these blood tests in the two, new 
follow-up strategy arms. If there are safety issues or adverse events, the general practitioner will contact 
HPs at the hospital. Patients, who normally take the 3-month blood tests at the hospital due to 
convenience, may continue this practice. Every 6th month the patients in the two intervention arms will 
take a photo of the laboratory test results and upload this in the MyDignio app. For the “Remote 
monitoring” study arm, the laboratory test results will be monitored each 6th month, whereas for the 
“Patient-initiated care”, the laboratory test results will only be used for research purposes after the 18-
month follow-up.  Additional tests may be performed at any time during the study as determined 
necessary by the medical doctor or required by local regulations. Medical doctors must document their 
review of each laboratory safety report. 
Table 6: Protocol-Required Safety Laboratory Tests 
Laboratory Tests Parameters 
Hematology 
Hemoglobin 
Red blood cells  
White blood cell count with Differential: Neutrophils, Lymphocytes, Monocytes, 
Eosinophils, Basophils 
Platelet Count 
Clinical 
Chemistry 
Creatinine 
Glomerular filtration rate 
Alanine transaminase 
 
 
 
 

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 Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
 
Definition of AE 
AE Definition 
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with 
the use of study intervention, whether or not considered related to the study intervention.  
 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of 
study intervention. 
Events Meeting the AE Definition 
 
Any abnormal laboratory test results or other safety assessments, including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment of the 
investigator. 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study intervention even though it may have been 
present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either TNFi or a concomitant 
medication. Intentional overdose taken with possible suicidal/self-harming intent should be 
reported regardless of sequelae. 
 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as 
AE or SAE if they fulfil the definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition 
 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the investigator to be more 
severe than expected for the participant’s condition. 
 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s condition. 
 
Medical or surgical procedure: the condition that leads to the procedure is the AE. 
 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected 
at the start of the study that do not worsen. 
 
 

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Definition of SAE 
An SAE is defined as any serious adverse event that, at any dose: 
a. 
Results in death 
b. 
Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant was 
at risk of death at the time of the event. It does not refer to an event, which hypothetically might 
have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been admitted (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician’s office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious 
criteria, the event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious. Hospitalization for elective treatment of a pre-
existing condition that did not worsen from baseline is not considered an AE. 
d. 
Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (e.g., sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
Medical or scientific judgment should be exercised by the investigator in deciding whether SAE 
reporting is appropriate in other situations such as significant medical events that may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other outcomes 
listed in the above definition. These events should usually be considered serious. 
 
 
Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
related to the event and record all relevant AE/SAE information. 
 
The investigator will attempt to establish a diagnosis based on signs, symptoms, and/or other 
clinical information, and whenever possible, this diagnosis will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will assess the intensity for each AE/SAE according to the following categories:  
 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
 
Moderate: An event that causes sufficient discomfort to interfere with normal everyday 
activities. 
 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with an SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 

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Assessment of Causality 
 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE and must document this review in the medical notes.  
 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than it not being ruled out. Clinical judgment 
and the Product Information is applied to determine the relationship. Alternative causes (e.g. 
underlying disease, concomitant therapy, other risk factors) and temporal relationship of the 
event to study intervention will be considered and investigated. 
 
Follow-up of AEs and SAEs 
 
The investigator is obligated to perform or arrange for any supplemental evaluations as medically 
indicated to elucidate the nature and/or causality of the AE or SAE as fully as possible.  
 
New or updated information will be recorded in the originally submitted documents. 
 
 
 
 

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 Appendix 5: ASAS Classification criteria for Axial Spondyloarthritis 
 
In patients with ≥3 months history of back pain and age of onset <45 years 
Sacroiliitis on imaging* and ≥1 SpA feature 
 
OR 
 
HLA B27 and ≥2 SpA features 
SpA- features 
 
Inflammatory back pain 
 
Arthritis 
 
Enthesitis (heel) 
 
Uveitis 
 
Dactylitis 
 
Psoriasis 
 
Inflammatory bowel disease 
 
Good response to NSAIDs 
 
Family history of SpA 
 
HLA B27 
 
Elevated CRP 
Sacroiliitis on imaging 
 
Active (acute) inflammation on MRI highly suggestive of sacroiliitis associated with SpA 
 
Definite radiographic sacroiliits according to the modified New York criteria 
 
 
 
 
 
 
 
 

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 Appendix 6: Patient-reported outcomes 
 
Patient global assessment  
 
 
Pain assessment 
 
 
 
 
 
 
 Joint pain assessment 
 
 
 
 
 
 
 
 Patient reported flare  
Har du sykdomsoppbluss (klar forverring) av din revmatiske sykdom nå? 
 Nei 
 Ja 
 Usikker 
Hvis du svarte «Ja» eller «usikker», hvilken dato startet forverringen?    __.__.20__  
 
Omtrent hvor mange dager varte forverringen/har forverringen vart?   _____dager   
 
 

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BASDAI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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BASFI 
Angi hvordan du greide følgende aktiviteter den siste uken:. 
 
1. Ta på strømper eller strømpebukser uten assistanse eller ved bruk av hjelpemiddel (for 
eksempel strømpe-påtrekker)? 
 
2. Bøye deg forover fra midjen for å plukke opp en penn fra gulvet uten å bruke et hjelpemiddel 
 
3. Nå opp til en høythengende hylle uten bruk av hjelpemidler (for eksempel gripetang). 
 
4. Reise deg fra en spisebordsstol uten armlener eller annen hjelp
 
5. Reise deg opp fra liggende stilling på gulvet uten hjelp? 
 
6. Stå oppreist uten støtte i 10 min. uten å få ubehag
 
7. Gå opp 12-15 trappetrinn uten å bruke rekkverk eller gåstøtte. En fot på hvert trinn
 
8. Se deg over skulderen uten å vri kroppen
 
9. Utføre fysisk krevende aktiviteter (for eksempel fysioterapiøvelser, hagearbeid eller sport). 
 
10. Utføre en hel dags aktiviteter enten hjemme eller på arbeid
 
 
 

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EQ-5D-5L 
 

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WPAI item no. 6 
 
 
 
 
Patient-reported global change in disease activity 
Sammenliknet med for 6 måneder siden, hvordan er din sykdomsaktivitet nå?  
 
 
 Patient-reported global change in activity impairment 
Sammenliknet med for 6 måneder siden, hvordan er din evne til å utføre vanlige, daglige aktiviteter, 
utenom arbeid, nå?  
 
 
 

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 Physical activity  
 
 
 

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 Patient satisfaction with care 
Hvor fornøyd er du alt i alt med den behandlingen du har fått for din revmatiske sykdom? 
 
 
 
 
Svært fornøyd       
Fornøyd        
Både og        
Misfornøyd        Svært misfornøyd 
 
 Medication use 
De siste 6 månedene, har du tatt medisin for din revmatiske sykdom som avtalt? 
 Nei 
 Ja 
 
Hvis nei: Hvor mange ganger har du ikke tatt medisinen de siste 6 månedene? ______  
 
De siste 6 månedene, har du fått kortison (injeksjon i ledd eller som tablett)? 
 Nei 
 Ja 
 
Hvis ja: Hva var årsaken til at du fikk kortison: _________________________________________ 
 
De siste 6 månedene, har du brukt NSAIDs (betennelsesdempende medikamenter)? 
 Nei 
 Ja 
 
Hvis ja: De siste 6 månedene, har du da brukt… 
 NSAIDs som en kur over en periode? 
 Enkelte NSAIDs tabletter nå og da? 
 
Hvis ja: Hvilken NSAIDs type (navn) brukte du? _____________________ 
Hvis ja: Hvor mange milligram tok du per dag? _____________________ 
Hvis ja: Hvor mange dager brukte du NSAIDs?  
 
 
 
 
 
 
 

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Hvis ja og som en kur: Hvilken dato startet du en NSAIDs kur?   __.__.___ 
 
Hvis ja og som en kur: Hvilken dato stoppet du en NSAIDs kur? __.__.___ 
 
 
De siste 6 månedene, har du brukt andre smertestillende medikamenter (andre enn 
betennelsedempende/NASAIDs)? 
 Nei 
 Ja 
 
Hvis ja, Oppgi navn på medikament, hvor mange milligram du brukte per dag og antall dager: 
___________________________________________________________________________  
 
 Time use and costs related to consultations  
1) Hvis du er i lønnet arbeid: Hva må du gjøre for å få fri fra arbeidet for å dra til Diakonhjemmet Sykehus  
 
Lønnet fravær fra arbeid 
 
 
 
 
Ulønnet fravær fra arbeid 
 
 
 
 
Jobber inn tiden senere/avspaserer 
 
 
 
Var utenfor arbeidstiden 
 
 
 
 
Tok ut ferie 
 
 
 
 
 
 
Andre ordninger 
 
 
 
   
Hvilken annen ordning må du gjøre for å få fri?____________________________ 
 
2) Omtrent hvor lang tid bruker du på å reise til Diakonhjemmet Sykehus (én vei)? 
Oppgi antall minutter:________ 
 
3) Omtrent hvor lang er reiseveien til Diakonhjemmet Sykehus (én vei)?  
Oppgi antall kilometer (km) én vei. _____________ 
 
4) Hva slags transportmiddel bruker du vanligvis for å reise til Diakonhjemmet Sykehus?  
Dersom du brukte flere typer transportmiddel, sett kryss for transportmiddelet du bruker lengst (i form 
av distanse). (Sett ett kryss) 
 
Går/sykler 
 
 
Privat bil 
 
 
Buss/T-bane/tog 
 
 
Taxi 
 
 
Fly 
 
Annet: 
   
 
Hvilket annet transportmiddel brukte du?: ___________ 
 

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5) Hvis bil: Kjører du bil selv eller blir kjørt?  
 
 
 
 
 
Kjører bil selv       Blir kjørt   
 
 
6) Hvis du blir kjørt: Må vedkommende ta seg fri fra arbeidet?  Nei   Ja     
     
 
 
 Digital self-efficacy 
 
 
 eHealth literacy 
20 items from 4 domains of the eHLQ33: 1) using technology to process health information, 2) ability to 
actively engage with digital services, 3) feel safe and in control, 4) motivated to engage with digital 
services. Response options for all items range from 1 (strongly disagree) to 4 (strongly agree). The 
instrument cannot be shown due to license requirements. 
 
 

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 Patient satisfaction with remote monitoring or patient-initated care 
22 items in the Service User Technology Acceptability Questionnaire (SUTAQ)39 reported at the 18-
months follow-up. While the remote monitoring arm will report all 22 items, the patient-initiated care 
arm will report on 3 of the 22 items (no. 1, 10 and 11). The usual care arm will not report on this 
questionnaire. 
 
 Appendix 8: Abbreviations and Definitions 
AE 
Adverse event 
ALT 
Alanine Transaminase 
ASAS 
Assessment of SpondyloArthritis International Society 
ASDAS 
Ankylosing Spondylitis Disease Activity Score 
AxSpA 
Axial spondyloarthritis 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI 
Bath Ankylosing Spondylitis Functional Index 
CIOMS 
Council for International Organizations of Medical Sciences 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case report file 
CRP 
C-reactive protein 
EQ5D 
Euro Quality of Life 5 dimensions 
ESR 
Erythrocyte Sedimentation Rate 
FAS 
Full analysis set 
GCP 
Good clinical practice 
GFR 
Glomerular Filtration Rate 
HLA-B27 
Human Leucocyte Antigen B27 
HP 
Health professional 
ICER 
Incremental Cost-Effectiveness Ratio 
ITT 
Intention to treat 
MRI 
Magnetic Resonance Imaging 

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NSAIDs 
Non-steroidal anti-inflammatory drugs 
NYHA 
New York Heart Association 
PGA 
Patient global assessment 
PPS 
Per protocol set 
PRO 
Patient-reported outcomes 
QALY 
Quality Adjusted Life Years 
RCT 
Randomized controlled trial 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SI-joints 
Sacroiliac joints 
SpA 
SpondyloArthritis 
TB 
Tuberculosis 
TNFi 
Tumor Necrosis Factor inhibitor 
VAS 
Visual analogue scale 
WPAI 
Work Productivity and Activity Impairment 
X-ray 
Conventional radiography 
 
 
 

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10 References 
1. 
Totten AM, Womack DM, Eden KB, et al. Telehealth: Mapping the Evidence for Patient 
Outcomes From Systematic Reviews. Rockville (MD): Agency for Healthcare Research and 
Quality (US): 2016. (https://www.ncbi.nlm.nih.gov/pubmed/27536752). 
2. 
McDougall JA, Ferucci ED, Glover J, Fraenkel L. Telerheumatology: A Systematic Review. Arthritis 
Care Res (Hoboken) 2017;69(10):1546-1557. DOI: 10.1002/acr.23153. 
3. 
Piga M, Cangemi I, Mathieu A, Cauli A. Telemedicine for patients with rheumatic diseases: 
Systematic review and proposal for research agenda. Semin Arthritis Rheum 2017;47(1):121-
128. DOI: 10.1016/j.semarthrit.2017.03.014. 
4. 
Norwegian Ministry of Health and Care Services. [In Norwegian: Nasjonal helse- og sykehusplan 
2020-2023]. 2019. (https://www.regjeringen.no/no/dokumenter/nasjonal-helse--og-
sykehusplan-2020-2023/id2679013/). 
5. 
Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369(9570):1379-1390. DOI: 
10.1016/S0140-6736(07)60635-7. 
6. 
Sepriano A, Regel A, van der Heijde D, et al. Efficacy and safety of biological and targeted-
synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR 
recommendations for the management of axial spondyloarthritis. RMD Open 
2017;3(1):e000396. DOI: 10.1136/rmdopen-2016-000396. 
7. 
Gossec L, Molto A, Romand X, et al. Recommendations for the assessment and optimization of 
adherence to disease-modifying drugs in chronic inflammatory rheumatic diseases: A process 
based on literature reviews and expert consensus. Joint Bone Spine 2019;86(1):13-19. DOI: 
10.1016/j.jbspin.2018.08.006. 
8. 
Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS. Impact of medication adherence on 
hospitalization risk and healthcare cost. Med Care 2005;43(6):521-30. DOI: 
10.1097/01.mlr.0000163641.86870.af. 
9. 
Dougados M, Baeten D. Spondyloarthritis. Lancet 2011;377(9783):2127-37. DOI: 10.1016/S0140-
6736(11)60071-8. 
10. 
Wang R, Ward MM. Epidemiology of axial spondyloarthritis: an update. Curr Opin Rheumatol 
2018;30(2):137-143. DOI: 10.1097/BOR.0000000000000475. 
11. 
Gossec L, Portier A, Landewe R, et al. Preliminary definitions of 'flare' in axial spondyloarthritis, 
based on pain, BASDAI and ASDAS-CRP: an ASAS initiative. Ann Rheum Dis 2016;75(6):991-6. 
DOI: 10.1136/annrheumdis-2015-208593. 
12. 
Sieper J, Braun J, Dougados M, Baeten D. Axial spondyloarthritis. Nat Rev Dis Primers 
2015;1:15013. DOI: 10.1038/nrdp.2015.13. 
13. 
Carli L, Calabresi E, Governato G, Braun J. One year in review 2018: axial spondyloarthritis. Clin 
Exp Rheumatol 2019;37(6):889-898. (https://www.ncbi.nlm.nih.gov/pubmed/31796161). 
14. 
Smolen JS, Schols M, Braun J, et al. Treating axial spondyloarthritis and peripheral 
spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by 
an international task force. Ann Rheum Dis 2018;77(1):3-17. DOI: 10.1136/annrheumdis-2017-
211734. 
15. 
van der Heijde D, Ramiro S, Landewe R, et al. 2016 update of the ASAS-EULAR management 
recommendations for axial spondyloarthritis. Ann Rheum Dis 2017;76(6):978-991. DOI: 
10.1136/annrheumdis-2016-210770. 
16. 
Regel A, Sepriano A, Baraliakos X, et al. Efficacy and safety of non-pharmacological and non-
biological pharmacological treatment: a systematic literature review informing the 2016 update 

CONFIDENTIAL 
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Doc. No. 2.01.1. Valid from March 2020.  
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of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open 
2017;3(1):e000397. DOI: 10.1136/rmdopen-2016-000397. 
17. 
Sveaas SH, Berg IJ, Provan SA, et al. Efficacy of high intensity exercise on disease activity and 
cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study. PLoS 
One 2014;9(9):e108688. DOI: 10.1371/journal.pone.0108688. 
18. 
Fongen C, Sveaas SH, Dagfinrud H. Barriers and Facilitators for Being Physically Active in Patients 
with Ankylosing Spondylitis: A Cross-sectional Comparative Study. Musculoskeletal Care 
2015;13(2):76-83. DOI: 10.1002/msc.1088. 
19. 
Gossec L, Guyard F, Leroy D, et al. Detection of Flares by Decrease in Physical Activity, Collected 
Using Wearable Activity Trackers in Rheumatoid Arthritis or Axial Spondyloarthritis: An 
Application of Machine Learning Analyses in Rheumatology. Arthritis Care Res (Hoboken) 
2019;71(10):1336-1343. DOI: 10.1002/acr.23768. 
20. 
Davergne T, Rakotozafiarison A, Servy H, Gossec L. Wearable Activity Trackers in the 
Management of Rheumatic Diseases: Where Are We in 2020? Sensors (Basel) 2020;20(17). DOI: 
10.3390/s20174797. 
21. 
Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk 
management in patients with rheumatoid arthritis and other forms of inflammatory joint 
disorders: 2015/2016 update. Ann Rheum Dis 2017;76(1):17-28. DOI: 10.1136/annrheumdis-
2016-209775. 
22. 
Wibetoe G, Ikdahl E, Rollefstad S, et al. Cardiovascular disease risk profiles in inflammatory joint 
disease entities. Arthritis Res Ther 2017;19(1):153. DOI: 10.1186/s13075-017-1358-1. 
23. 
Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease 
prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology 
and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by 
representatives of 10 societies and by invited experts)Developed with the special contribution of 
the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 
2016;37(29):2315-2381. DOI: 10.1093/eurheartj/ehw106. 
24. 
Jacquemin C, Maksymowych WP, Boonen A, Gossec L. Patient-reported Flares in Ankylosing 
Spondylitis: A Cross-sectional Analysis of 234 Patients. J Rheumatol 2017;44(4):425-430. DOI: 
10.3899/jrheum.160838. 
25. 
Machado PM, Landewe R, Heijde DV, Assessment of SpondyloArthritis international S. 
Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for 
disease activity states. Ann Rheum Dis 2018;77(10):1539-1540. DOI: 10.1136/annrheumdis-
2018-213184. 
26. 
Molto A, Gossec L, Meghnathi B, et al. An Assessment in SpondyloArthritis International Society 
(ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on 
ASDAS. Ann Rheum Dis 2018;77(1):124-127. DOI: 10.1136/annrheumdis-2017-212178. 
27. 
Derakhshan MH, Pathak H, Cook D, et al. Services for spondyloarthritis: a survey of patients and 
rheumatologists. Rheumatology (Oxford) 2018;57(6):987-996. DOI: 
10.1093/rheumatology/kex518. 
28. 
Hehir M, Mitchell K, Hewlett S. What happens in rheumatoid arthritis out-patient clinics? 
Rheumatology 2001;40:146. 
29. 
McBain H, Shipley M, Olaleye A, Moore S, Newman S. A patient-initiated DMARD self-monitoring 
service for people with rheumatoid or psoriatic arthritis on methotrexate: a randomised 
controlled trial. Ann Rheum Dis 2016;75(7):1343-9. DOI: 10.1136/annrheumdis-2015-207768. 

CONFIDENTIAL 
Protocol ReMonit, version 1.1 
 
Doc. No. 2.01.1. Valid from March 2020.  
Only the electronic version is valid. 
Side 58 av 58 
 
www.norcrin.no 
30. 
McBain H, Newman S, Shipley M, Olaleye A, Moore S. Experiences of a patient-initiated self-
monitoring service in inflammatory arthritis: A qualitative exploration. Musculoskeletal Care 
2018;16(2):278-286. DOI: 10.1002/msc.1232. 
31. 
de Thurah A, Stengaard-Pedersen K, Axelsen M, et al. Tele-Health Followup Strategy for Tight 
Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial. 
Arthritis Care Res (Hoboken) 2018;70(3):353-360. DOI: 10.1002/acr.23280. 
32. 
de Thurah AS, S.; Maribo, T.; Hjøllund, N.H.; Kruse, M. Cost effectiveness of tele-health follow-up 
in rheumatoid arthritis based on a non-inferiority randomized controlled trial. Ann Rheum Dis 
2020;79:Suppl 1. 
33. 
Kayser L, Karnoe A, Furstrand D, et al. A Multidimensional Tool Based on the eHealth Literacy 
Framework: Development and Initial Validity Testing of the eHealth Literacy Questionnaire 
(eHLQ). J Med Internet Res 2018;20(2):e36. DOI: 10.2196/jmir.8371. 
34. 
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining 
disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J 
Rheumatol 1994;21(12):2286-91. (https://www.ncbi.nlm.nih.gov/pubmed/7699630). 
35. 
EuroQol G. EuroQol--a new facility for the measurement of health-related quality of life. Health 
Policy 1990;16(3):199-208. DOI: 10.1016/0168-8510(90)90421-9. 
36. 
Kurtze N, Rangul V, Hustvedt BE, Flanders WD. Reliability and validity of self-reported physical 
activity in the Nord-Trondelag Health Study: HUNT 1. Scand J Public Health 2008;36(1):52-61. 
DOI: 10.1177/1403494807085373. 
37. 
Buysse DJ, Reynolds CF, 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality 
Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28(2):193-
213. DOI: 10.1016/0165-1781(89)90047-4. 
38. 
Skudal KE, Garratt AM, Eriksson B, Leinonen T, Simonsen J, Bjertnaes OA. The Nordic Patient 
Experiences Questionnaire (NORPEQ): cross-national comparison of data quality, internal 
consistency and validity in four Nordic countries. BMJ Open 2012;2(3):e000864. (PM:22649175). 
39. 
Hirani SP, Rixon L, Beynon M, et al. Quantifying beliefs regarding telehealth: Development of the 
Whole Systems Demonstrator Service User Technology Acceptability Questionnaire. J Telemed 
Telecare 2017;23(4):460-469. DOI: 10.1177/1357633X16649531.