bluuebunny/crossref_metadata_2025 huggingface dataset:
P159 Current patient reported outcomes (PROs) poorly reflect changes in lung function in patients with systemic sclerosis
Authors: Danzo Fiammetta , Gjeloshi Klodian , Abignano Giuseppina , Dean Anne-Maree , Masini Francesco , Cuomo Giovanna , del Galdo Francesco
Published: April 2020

Background

In a recent clinical trail the reduction of FVC was not accompanied by a benefit with respect to health-related quality of life and patient-reported outcomes (PROs). The aim of this study is to assess how the change in Pulmonary Function Test (PFTs) parameters correlates with the patient reported outcomes (PROs) in an observational cohort of patients with systemic sclerosis (SSc).

Methods

We conducted a retrospective study of 330 clinic episodes from 121 unselected patients diagnosed with systemic sclerosis according to EULAR/ACR 2013 criteria, in annual follow-up (for a total of 165 patients/year) with PFTs, Health Assessment Questionnaire Disability Index (HAQ-DI), Scleroderma Health Assessment Questionnaire (sHAQ), Modified Borg Dyspnea Scale (Borg) and Cochin Hand Function Score (CHFS). We assessed the correlation between the HAQ and the Visual Analogical Scale 1-7 at baseline (VAS1 pain, VAS2 disease severity, VAS3 arthritis activity, VAS4 intestinal problems, VAS5 dyspnea, VAS6 Raynaud’s phenomenon, VAS7 digital ulcers). We evaluated the correlation of PFTs with PROs at every time period and the correlation between the change of PFTs parameters (δFVC, δDLCO) with the change of the PROs over a year of follow-up. Following analysis of distribution, Spearman or Pearson Test were used to determine correlation coefficients, as appropriate (Prism 7).

Results

The median disease duration was 5 years (IQR 3-10). The median of 12 months δFVC% and δDLCO% were 0 (IQR -5.81 to 3.28) and -2.439 (IQR -8.76 to 5.98), respectively. The analysis evidenced a strong positive correlation between VAS1-7 and HAQ. We observed also significant correlation between FVC%, DLCO% and HAQ-DI (r= -0.355 and -0.266, respectively; p < 0.0001 for both), Borg (r= -0.403 and -0.379, respectively; p < 0.0001) and CHFS (r = -0.355 and -0.256, respectively; p < 0.0001). Nevertheless, in longitudinal setting there was no significant correlation between δPROs and changes lung function, as continuous variables, neither there was any significant PROs difference in patients that did or did not lose more than 10% of FVC and DLCO over a year of follow-up.

Conclusion

This analysis of a monocentric non-selected population evidenced that the current commonly used PROs in SSc while showing a good correlation with lung function are poorly sensitive to change or to reflect changes in lung function over 12 months. In this sense, prudent interpretation of the lack of correlation between FVC and patient-reported outcomes in studies of phase 3 is warranted.

Disclosures

F. Danzo: None. K. Gjeloshi: None. G. Abignano: None. A. Dean: None. F. Masini: None. G. Cuomo: None. F. del Galdo: None.
P173 Progression of subclinical cardiovascular disease in SLE: a five year follow up study
Authors: Bakshi Jyoti , Griffin Maura , Croca Sara , Farhina Filipa , Isenberg David , Nicolaides Andrew , Rahman Anisur
Published: April 2020

Background

Patients with SLE have 5-10-fold increased risk of developing CVD compared to age and sex-matched controls. The average age of developing a first CVD event in patients with SLE is only 49. In this study we aimed to describe the rate and determinants of carotid plaque progression in a cohort of SLE patients who were asymptomatic of CVD at baseline.

Methods

We carried out vascular ultrasound studies of 100 patients with SLE asymptomatic of CVD at baseline. Sixty-nine patients were rescanned over a median of 5 years of follow up. Ninety-four percent who were re-scanned were women and the mean overall age was 46 years (SD 11). Clinical and CVD risk was assessed at baseline and follow up. The same protocol for assessment at baseline using B-mode Doppler ultrasound to measure intimal media thickness and plaque was used at follow up to assess progression. We also assessed total plaque area (TPA), a more sensitive measure of plaque, and echolucency expressed as gray scale median (GSM) which is linked to plaque lipid content.

Results

Of the 100 patients with a baseline scan, 69 patients had a second scan at a median of 5 years follow up. New plaque developed in 9% and 26% had an increase in plaque number. The mean overall IMT (0.111 vs 0.064, p < 0.01) and common carotid IMT (0.065 vs 0.055, p < 0.01) were significantly raised in plaque vs non-plaque patients. In a multi -variable analysis CIMT at follow-up was independently associated with age (beta 0.415, p < 0.001) and diastolic blood pressure (beta 0.285, p < 0.021). Independent predictors of plaque at follow-up scan on multi-variable analysis were age at scan>52 years (OR 10.41, CI 2.66-40.80) and systolic BP > 133 (OR 5.26, CI 1.396 - 19.862). In contrast, total cholesterol was negatively correlated with TPA (beta = -1.167, p = 0.002) and with GSM (beta = -0.513, p = 0.012).

Conclusion

Amongst these 69 patients, 26% had increased plaque and none had decreased plaque over a median of five years follow-up. Measurement of novel ultrasound variables such as TPA and echolucency may identify more modifiable risk factors that can be used to improve CVD outcomes in patients with SLE.

Disclosures

J. Bakshi: None. M. Griffin: None. S. Croca: None. F. Farhina: None. D. Isenberg: None. A. Nicolaides: None. A. Rahman: None.
P177 Art in dialogue: art and voice in an ANCA-associated vasculitis workshop
Authors: Perera Shanali , Krafcsik Dijana , Rutherford Peter
Published: April 2020

Background

Using art to facilitate 'expressions of illness experience’ can provide new ways of helping healthcare professionals and others gain a deeper understanding of the impact that illnesses can have. Using art as a non-verbal communication tool may provide a voice for people with ANCA-associated vasculitis (AAV), as well as a space for their carer to reveal lived experiences of AAV. This can open communication channels in the patient-clinician or carer/support interview. Furthermore, art could be used as a coping mechanism for rare diseases such as AAV and could have therapeutic effects.

Methods

A workshop for people with AAV was held for participants to express their individual AAV using digital art, as either a patient, a carer or healthcare provider (n = 6). We employed a personal narrative inquiry and a digital art exercise focusing on patients', carer's and the clinicians' perceptions on what pain, fatigue, change and support look like in colour and shape.

Results

As an artist, the first author presented her own dialogue and agency of being an artist, patient and retired rheumatologist. We invited a collective understanding of ‘how people make sense of key life experiences and what it means to them’. For all participants, using a digital art workshop to express the patient journey and experiences with pain and fatigue was a new experience. The participants used different types of expressions in their art. Some individuals used art for storytelling, some used more abstract art with different digital brush techniques to express their feelings of pain, fear or hope. The colour theme was discussed with the participants. Red/orange was intuitively used to represent pain whereas green/blue was used to represent periods of calm. People who said they were less expressive could also use this form of non-verbal communication. Participants expressed their feelings and experiences and highlighted when painting with digital art that using the finger was easier and less tiring than holding a brush. Others found that while concentrating on creating the picture, they found some relief from illness-related symptoms.

Conclusion

This workshop used colour and shape to portray different energies surrounding adaptations and transitions that AAV had for patients, carer and clinicians. Digital art helped to express illnesses and emotions that AAV patients or carers experience and could be used as a method for coping. It may open up channels in the patient-clinician or carer/support dialogue and break communication barriers in healthcare encounters, leading to better monitoring results. Art encourages self-reflection, and can influence, inspire and enable individuals. It helps us to see more of the face behind the illness, not just the person with an illness.

Disclosures

S. Perera None. D. Krafcsik Corporate appointments; Employee of Vifor Pharma. P. Rutherford Corporate appointments; Employee of Vifor Pharma. Shareholder/stock ownership; Vifor Pharma.
P180 External validation of the Southend GCA Probability Score (GCAPS) as a screening tool for referrals with possible GCA
Authors: Quick Vanessa , Hughes Mark , Mothojakan Nadira , Fishman Daniel
Published: April 2020

Background

We run a rheumatologist-led, ultrasound-driven giant cell arteritis (GCA) fast track pathway (FTP). Currently, no specific referral criteria are required. Sensitive referral criteria are now needed to safely reduce referrals, which have risen year-on-year (92 in Year 3, 84% greater than Year 1).

Methods

The following were collected for all patients referred to our GCA-FTP from 1/4/2018-31/3/2019 (Year 3): Final diagnosis of imaging/biopsy confirmed-GCA, unconfirmed clinical-GCA or not-GCA using the electronic patient record to September 2019; Rheumatologist-determined clinical probability of GCA (low, moderate, high) before imaging/biopsy; Presence of ≥ 3 ACR 1990 GCA Classification Criteria (biopsy excluded, adapted to increase sensitivity, see table); Presence of Southend GCAPS≥10 (Based on our clinical experience, polymyalgic symptoms were also counted if patients had recently taken prednisolone for PMR).

Results

88 consecutive patients were analysed (total 92: 2 missing data; 2 passed through twice). 25/88 (27%) were diagnosed with GCA 24 were imaging/biopsy confirmed. The single patient with unconfirmed clinical-GCA had high clinical probability, indeterminate ultrasound and biopsy after >1-week glucocorticoid. GCA patients were mean age 77.3y (range 63-94), 76% female, all White, with mean GCAPS 15.3 (range 10-25).

Our adaptations of the ACR criteria increased ACR-criteria sensitivity: 24% GCA patients had new generalised headache and 16% had ESR<50, but CRP>10. 14% referrals were non-White, although GCA is rare in this group. GCAPS was based on a largely White population. If GCAPS did not remove 3 points for alternative diagnoses, then 5 additional non-White patients would have scored ≥10.

Conclusion

This study externally validates GCAPS≥10 as a screening tool for referrals with possible GCA. It captured all GCA patients and screened out 44% referrals. For this indication, it performed better than a consultant rheumatologist. Despite adaptations to improve sensitivity, ACR criteria missed a quarter of cases. To improve GCAPS specificity when scored by a non-rheumatologist, GCAPS should be adapted to reflect the low likelihood of GCA in non-Whites. We plan to only accept patients with GCAPS≥10, where 3 points are removed for non-Whites if not already removed for alternative diagnoses. We predict referrals will reduce but anticipate referrers will need education to limit over-scoring.

Disclosures

V. Quick None. M. Hughes None. N. Mothojakan None. D. Fishman None.
P191 Real life experience of tocilizumab for the management of giant cell arteritis in Fife, Scotland
Authors: Allcoat Paul , Hart Stephanie , Hailwood Sarah J , McLaren John S
Published: April 2020

Background

Tocilizumab was accepted by the Scottish Medicines Consortium for use in the management of Giant Cell Arteritis (GCA) on 10.09.18. The Fife Rheumatic Diseases Unit is the first Rheumatology unit in Scotland to introduce a structured process for the management of GCA patients with tocilizumab. We describe here our experience of this new service for NHS Fife.

Methods

All GCA patients considered for tocilizumab are discussed at our weekly Medication Review Meeting by the Consultant Rheumatologists (JSM & SJH) and Rheumatology Pharmacist (SH). By consensus decision, GCA patients deemed appropriate for tocilizumab treatment are then referred to the Vasculitis Nurse Specialist (VNS; PA) for counselling. We have prospectively recorded data on all GCA patients counselled on tocilizumab from 08.11.18 onwards. Patients are followed up closely in a structured manner by the VNS on a fortnightly basis, with both clinical and laboratory assessment at each visit. The VNS ensures that GCA patients follow a rapid steroid taper in line with that used in the GiACTA Trial. Patients also have laboratory assessments performed between each VNS visit at their GP's surgery (to monitor the ESR) to assist in decision making in view of the rapid steroid taper. The VNS also records the cumulative steroid dose along with drug-related side effects (both from steroids and tocilizumab).

Results

14 GCA patients have been counselled and commenced on tocilizumab between 08.11.18 and 18.09.19. We have another 2 GCA patients awaiting counselling and due to start tocilizumab soon. Twelve patients have newly diagnosed GCA (5 with unilateral visual loss), 5 with Large vessel vasculitis and 3 patients have refractory GCA. Of the newly diagnosed patients, the reasons for initiating tocilizumab were as follows: poor control of diabetes mellitus on high dose steroids; large vessel vasculitis confirmed on PET scan; previous long-term steroid exposure due to past history of polymyositis; high osteoporotic risk.

Conclusion

We have successfully introduced a structured process for the use of tocilizumab in Fife GCA patients via a VNS-led GCA clinic. This ensures robust clinical governance around the issues of safety, efficacy and cost. In addition, by collecting real life prospective data, we will add to the existing information available regarding use of this new therapeutic advance for GCA management in routine clinical practice. This initiative is the first of its kind in Scotland and a new service development for NHS Fife.

Disclosures

P. Allcoat None. S. Hart None. S.J. Hailwood None. J.S. McLaren Honoraria; J.S.M. has received Speaker fees from Roche.
P197 Analgesic prescribing in patients with inflammatory arthritis in the NHS
Authors: Scott Ian C , Bailey James , White Christopher , Mallen Christian D , Muller Sara
Published: April 2020

Background

There is little evidence analgesics improve pain in inflammatory arthritis (IA), and substantial evidence they have significant harms. Excepting NSAIDs in ankylosing spondylitis (AS), their long-term use is not recommended in guidelines. Despite this, international data suggest pain management in IA involves the substantial and sustained use of opioids (∼40% of North American patients with rheumatoid arthritis [RA] are chronic opioid users). We evaluated analgesic prescribing practice in NHS-managed patients with IA.

Methods

This study was undertaken in the Consultations in Primary Care Archive (CiPCA), containing primary care consultation/prescription data from 9 general practices (∼200,000 patients) in North Staffordshire (UK) from 2000-2015. Repeated cross-sectional analyses evaluated annual prevalence of analgesic prescriptions in (a) patients with IA (RA; psoriatic arthritis [PsA]; AS), and (b) five age, sex, and practice-matched controls without inflammatory rheumatic conditions. Patients without full calendar-years of data were excluded. The numerator was the number of patients receiving oral analgesic prescriptions in a calendar-year; the denominator was the number of patients contributing data within that calendar-year. Analgesic prescriptions were classified into basic, opioids, gabapentinoids, and NSAIDs. Patients were grouped into users, or non-users of analgesics. Users were sub-classified into chronic (≥3 prescriptions across a calendar year), or intermittent (1-2 prescriptions) users.

Results

In all years, the majority (65.1-77.8%) of patients with IA received analgesics, compared with the minority (38.1-42.0%) of controls (Table). Opioid prescribing in IA fell slightly between 2000-2015, but remained common with 45.0% receiving an opioid, and 32.5% being chronic opioid users in 2015. The proportion of patients with IA prescribed gabapentinoids increased from 0% in 2000, to 9.4% in 2015. In contrast, the proportion prescribed NSAIDs fell from 53.3% in 2000, to 24.9% in 2015. In all years, analgesic use was commoner in patients with RA, compared to PsA and AS, and 2-4 times higher in IA than controls.

Conclusion

Analgesic prescribing - particularly opioids - in IA is commonplace, with most prescribed long-term. This is at variance with existing evidence, and guidelines. Interventions are needed to improve analgesic prescribing in this population.

Disclosures

I.C. Scott None. J. Bailey None. C. White None. C.D. Mallen None. S. Muller None.
P207 A quality improvement intervention to increase pneumococcal and influenza vaccination rates in immunosuppressed inflammatory arthritis patients
Authors: Murray Kieran , Low Candice , Young Francis , O'Rourke Anna , Callanan Ian , Feeney Eoin , Veale Douglas J
Published: April 2020

Background

Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group.

Methods

In 2017, Rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease modifying antirheumatic drugs (csDMARDs) or biologics (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis.

Results

425 patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥60 years old). From 2017-2018, vaccination rates increased for PPSV23 {41.0% to 47.2% (p = 0.29)} and influenza {61.8% to 62.1% (p = 0.95)}. The most common reason for non-vaccination was lack of awareness. Following the intervention, this decreased for influenza (36.7% to 34.2%) and PPSV23 (82.1% to 76.4%). General Practitioners performed most vaccinations, only 3.6% were delivered in hospital. Significant predictors of PPSV23 vaccination were older age {≥80 years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared to ≤ 39 years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013) and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P < 0.001). Up to date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P < 0.001) predicted influenza vaccination.

Conclusion

PPSV23 and influenza vaccination rates were suboptimal and increased marginally. Point-of-care vaccination may be more effective.

Disclosures

K. Murray: None. C. Low: None. F. Young: None. A. O'Rourke: None. I. Callanan: None. E. Feeney: None. D. Veale: None.
P237 Utility of diagnostic ultrasound in a rheumatology podiatry clinic
Authors: Newcombe Lisa , Tougher John , Woodburn James , Barn Ruth
Published: April 2020

Background

The use of musculoskeletal ultrasound (MSUS) is increasing with diagnostic, prognostic and treatment advantages for inflammatory disease. However, further work is required to determine its utility in podiatry clinics regarding diagnosis and management of lower limb pathology. The overall objective was to investigate the agreement between clinical and MSUS diagnoses and the impact of MSUS on treatment planning.

Methods

Consecutive patients attending a rheumatology clinic at the Queen Elizabeth University Hospital Podiatry Department, Glasgow were invited to participate. Clinical diagnosis of foot problems and structures affected was conducted by a single experienced podiatrist (JT). MSUS assessment of affected structures was then conducted by a single podiatrist with US training (LN) using an Esaote MyLabAlpha portable US machine using two linear array transducers (IH6-18 and SL2325) with a range of 6-18MHz. Ultrasound findings were made available to the podiatrist responsible for diagnosis and management (JT) and any amendments to the diagnosis or treatment plan were recorded.

Results

A total of 23 participants were recruited, 7 male and 16 female with a mean (SD) age of 54 (14) years. Across a range of pathologies, agreement between clinical examination and MSUS was 55% (Table 1). Where disagreement occurred, a range of additional findings were reported from MSUS including bursae, osteomyelitis, active inflammation (joint and tendon) and gout. MSUS assessment confirmed the treatment plan for 15 patients (65%) and altered the treatment plan for 8 patients (35%). The alterations included: 2 onward referrals for further imaging/antibiotic therapy; 4 rehabilitation programme adjustments (based on presence or absence of active inflammation); 2 orthotic plan adjustments; and 2 where corticosteroid injection was no longer indicated.

Conclusion

When compared with an experienced clinician’s clinical diagnosis of foot pathology, MSUS agreed in just over half of the cases. Additional diagnostic findings from MSUS were reported in 45% of the sample. One third of the management plans were amended due to MSUS findings. Further work is required in a larger sample, but these findings provide provisional evidence of the utility of MSUS for enhancing the accuracy of diagnosis and the tailored management of lower limb pathology in rheumatology.

Disclosures

L. Newcombe None. J. Tougher None. J. Woodburn None. R. Barn None.
P241 Associations between clinical variables and psychological symptoms in RA: a network science perspective
Authors: Tung Hsiu Yen , Norton Sam , Galloway James , Matcham Faith , Hotopf Matthew
Published: April 2020

Background

This study tests the feasibility of a network analysis approach to examine associations between clinical variables and mental health symptoms in rheumatoid arthritis (RA).

Methods

Over 1,000 patients completed patient reported outcomes. A sub-sample of 211 was extracted where psychological screening (using two-item versions of the Patient Health Questionnaire (PHQ2) and the Generalised Anxiety Disorder scale (GAD2)) and inflammatory markers were recorded concurrently (<14days). Inflammatory markers, joint counts, pain, fatigue, and global disease activity were also recorded. Network analysis was conducted based on egularised correlations between variables.

Results

The network highlights pain and PHQ2 (low mood) as having the highest degree (3.9 & 3.8) and betweenness centrality (22 & 10), indicating that they have the highest number of connections and provide the shortest pathway between symptoms, therefore act as key variables linking inflammation and mental health. Pain and global disease activity had the highest closeness centrality (0.033 & 0.032), illustrating that they have the shortest path with other symptoms, and capture the influence of both inflammation and mental health. Tender and swollen joints have weak connections with mental health variables, suggesting that extra-articular aspects of pain may be important.

Conclusion

Inflammation in RA does not have a strong influence on mental health, but pain appears to be the biggest influencing factor. Symptoms of mental health were all strongly connected, but low mood provides the main connection between clinical and psychological variables. This indicates mood as potentially a key variable, which is easy to monitor in routine care.

Disclosures

H. Tung None. S. Norton None. J. Galloway None. F. Matcham None. M. Hotopf None.
P254 Secukinumab provides rapid and sustained improvement in joint tenderness and swelling in patients with PsA: 2-year results from the Phase 3 FUTURE 5 study
Authors: McInnes Iain , Chinoy Hector , Asquith Darren , White Abigail , Gaillez Corine
Published: April 2020

Background

Tender joint count (TJC) and swollen joint count (SJC) are components of composite measures used to assess treatment response, which may be impacted by confounding factors. TJC and SJC used in psoriatic arthritis (PsA), which can affect small joints of the feet, assess 78 and 76 joints. TJC and SJC are effective measures of synovitis, a key measure of disease activity. We report 16-week through 2-year effects of secukinumab upon 78 TJC and 76 SJC in PsA patients in FUTURE 5.

Methods

996 patients with active PsA were randomised to subcutaneous secukinumab 300 mg with loading dose (LD), 150 mg with LD, 150 mg without LD or placebo. All patients received secukinumab or placebo at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter. Placebo-treated patients were re-randomised to secukinumab 300 or 150 mg at Week 16 (non-responders) or 24 (responders). Secukinumab dose was escalated from 150 to 300 mg starting at Week 60 and maintained thereafter, if active signs of disease were observed by the physician. 78 TJC and 76 SJC were assessed at baseline, Weeks 1, 2, 3 and 4, every 4 weeks until Week 52, every 8 weeks until Week 92 and at Week 104. ACR20 response, 78 TJC and 76 SJC results are reported for the overall population over 2 years of treatment. Data are reported as observed.

Results

Baseline characteristics were comparable across treatment arms (Table 1). 783/996 (78.6%) patients completed 104 weeks of treatment. All secukinumab dose regimens (300 mg with LD, 150 mg with LD and 150 mg without LD) demonstrated rapid-onset ACR20 responses that were superior to placebo at Week 16 (adjusted P values: P < 0.0001 for all secukinumab regimens) and increased to 77.0%, 79.4% and 82.4% at Week 104, respectively. Adjusted 78 TJC and adjusted 76 SJC improved in all secukinumab groups vs placebo by Week 4 through Week 16 and were sustained after 2 years of treatment (Table). Numerical differences were comparable between secukinumab doses.

Conclusion

Secukinumab provided rapid and sustained improvements in 78 TJC and 76 SJC over 2 years of treatment in patients with active PsA.

Disclosures

I. McInnes: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Honoraria; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. H. Chinoy: Honoraria; Novartis. D. Asquith: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. White: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. C. Gaillez: Shareholder/stock ownership; Novartis, Bristol-Myers Squibb. Other; Employee of Novartis.
P283 Clinical predictors of switching biologic treatment in patients PsA: data from a single centre over 17 years
Authors: Naja Meena , Santos Liliana R , Greenwood Mandy , Castelino Madhura
Published: April 2020

Background

Management of PsA has included biologic agents (bDMARDs) since the early 2000s, in addition to conventional disease-modifying antirheumatic drugs (csDMARDs). Switching of bDMARD treatment is currently common clinical practice in treatment failure. Our aims were to determine the most prescribed first line bDMARDs, reasons for switching and any clinical factors at baseline that may predict switching in PsA.

Methods

Data was analysed retrospectively from a cohort of 400 PsA patients followed through from 2002-2019. Statistical analysis was carried out (logistic regression, analysis of variance and descriptive statistics) using SPSS version 22.

Results

The median age at baseline was 38.4 years (interquartile range [IQR] 29.8 - 53.3 years), 52.5% were female. bDMARDs were started in 220 of the 400 patients (55.0%). Initial therapy was a TNFi in 212 patients (96.3%). The median age of those started on bDMARDs was 33.7 years (IQR 27.5 - 48.2 years), 52.5% were female. The most frequently prescribed was adalimumab (59.5%), followed by etanercept (33.2 %) and infliximab (3.2%). 106 out of the 220 patients (48.2%) were on at least one concomitant csDMARD. 83 patients (37.8%) switched to a second bDMARD; 69 of these (83.1%) switched to a second TNFi. The commonest reasons for switching were primary or secondary inefficacy (61.0%) and adverse events (33.7%). The median duration on the first bDMARD was 11.6 months (IQR 3.8 - 30.1 months). Of the 83 patients who commenced a second bDMARD, 45 (54.2%) switched to a third bDMARD. The median duration on the second bDMARD was 10.0 months (IQR 3.0 - 33.0 months). The main reasons for the second switch were primary or secondary inefficacy (44.4%), adverse events (42.2%) and a combination of the two (11.1%). Patients who switched onto a second bDMARD were more frequently female (57.8%), had longer disease duration (14.01 versus 13.2 years), higher pain scores (84.2 versus 66.0) and higher tender/swollen joint counts compared to non-switchers at baseline. Patients using csDMARDs at baseline were more often responsive to initial bDMARD treatment than those on bDMARD alone (63.2% response versus 45.1%), but this was not statistically significant (p value >0.05). There was no significant change in drug survival of the first bDMARD if the patient was concurrently taking csDMARDS. A high ESR at baseline was associated with increased risk of switching from a second bDMARD to a third (odds ratio 1.20, p = 0.036).

Conclusion

We found that females, those with longer disease duration, higher subjective elements to disease activity at baseline were more likely to switch from initial bDMARD therapy. A high baseline ESR was associated with switching onto a third line bDMARD. Interestingly, the concurrent use of csDMARDs had no significant effect on the drug survival or efficacy of bDMARD therapy.

Disclosures

M. Naja None. L. R. Santos None. M. Greenwood None. M. Castelino None.
Prevalence and impact of comorbidities in axial spondyloarthritis: systematic review and meta-analysis
Authors: Zhao Sizheng Steven , Robertson Selina , Reich Tzvi , Harrison Nicolas L , Moots Robert J , Goodson Nicola J
Published: April 2020

Objectives

Comorbidities are common in people with axial spondyloarthritis (axSpA). In this systematic review and meta-analysis, we aimed to: (i) describe the prevalence of commonly reported comorbidities, (ii) compare comorbidities between axSpA and control populations, and (iii) examine the impact of comorbidity burden on axSpA outcomes.

Methods

We systematically searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We excluded studies of only one comorbid condition or a few closely related diseases within one organ system. Where possible, meta-analysis was performed using random-effects models.

Results

A total of 40 studies were included for analysis. 36 studies reported prevalence of comorbidities, amounting to a combined sample size of 119 427 patients. The number of comorbidities studied ranged from 3 to 43. The most prevalent individual comorbidities were hypertension (pooled prevalence 23%), hyperlipidaemia (17%) and obesity (14%). Eleven studies consistently showed higher prevalence of comorbidities in axSpA than controls, particularly large differences were seen for depression [pooled odds ratio (OR) 1.80] and heart failure (OR 1.84). Comorbidities (total number of and individual conditions) were also associated with axSpA disease activity, functional impairment, quality of life, work productivity and mortality.

Conclusions

Comorbidities are common in axSpA, particularly cardiovascular diseases and risk factors. Most comorbidities were more prevalent in axSpA patients than in control populations. Overall comorbidity burden, and many individual conditions, were associated with axSpA outcomes including worse disease severity, work productivity and mortality.
A roadmap to target interleukin-6 in osteoarthritis
Authors: Wiegertjes Renske , van de Loo Fons A J , Blaney Davidson Esmeralda N
Published: April 2020

Joint inflammation is present in the majority of OA patients and pro-inflammatory mediators, such as IL-6, are actively involved in disease progression. Increased levels of IL-6 in serum or synovial fluid from OA patients correlate with disease incidence and severity, with IL-6 playing a pivotal role in the development of cartilage pathology, e.g. via induction of matrix-degrading enzymes. However, IL-6 also increases expression of anti-catabolic factors, suggesting a protective role. Until now, this dual role of IL-6 is incompletely understood and may be caused by differential effects of IL-6 classic vs trans-signalling. Here, we review current evidence regarding the role of IL-6 classic- and trans-signalling in local joint pathology of cartilage, synovium and bone. Furthermore, we discuss targeting of IL-6 in experimental OA models and provide future perspective for OA treatment by evaluating currently available IL-6 targeting strategies.
Classification vs diagnostic criteria: the challenge of diagnosing axial spondyloarthritis
Authors: Poddubnyy Denis
Published: April 2020

In recent years, significant progress has been made in improving the early diagnosis of spondyloarthritides (SpA), including axial SpA. Nonetheless, there are still issues related to the application of classification criteria for making the primary diagnosis of SpA in the daily practice. There are substantial conceptional and operational differences between the diagnostic vs classification approach. Although it is not possible to develop true diagnostic criteria for natural reasons as discussed in this review, the main principles of the diagnostic approach can be clearly defined: consider the pre-test probability of the disease, evaluate positive and negative results of the diagnostic test, exclude other entities, and estimate the probability of the disease at the end. Classification criteria should only be applied to patients with an established diagnosis and aimed at the identification of a rather homogeneous group of patients for the conduction of clinical research.
Cannabis Use Linked to Altered Functional Connectivity of the Visual Attentional Connectivity in Patients With Psychosis and Controls
Authors: Sami Musa Basseer , McCutcheon Robert A , Ettinger Ulrich , Williams Steve , Lythgoe Dave , McGuire Philip , Bhattacharyya Sagnik
Published: April 2020

Background

Both chronic cannabis use and psychotic disorders are associated with abnormalities in visual attentional processing. Using functional magnetic resonance imaging (fMRI), we sought to determine whether there would be a difference in functional connectivity in patients and controls with and without a history of cannabis use in the visual and dorsal attention networks.

Methods

Resting-state fMRI data were acquired in patients with early psychosis with (EPC = 29) and without (EPNC = 25); and controls with (HCC = 16) and without (HCNC = 22) cannabis use.

Results

There was a patient effect in both Visual-Dorsal Attention Internetwork (F(1,87) = 5.326, P = .023) and the Visual Network (F(1,87) = 4.044, P = .047) and a cannabis effect in the Dorsal Attention Network (F(1,87) = 4.773, P = .032). These effects were specific to the networks examined with no evidence for significant patient or cannabis effects in other canonical networks. Patients with a history of cannabis use showed increased connectivity in the Dorsal Attention Network (134%, P = .019) and Visual Dorsal Attention Internetwork (285%, P = .036) compared to non-using controls. In the EPC group connectivity of the Visual Network (ρ = 0.379, P = .042) and Visual-Dorsal Attention Internetwork (ρ = 0.421, P = .023) correlated with visual hallucinations which were significantly different from EPNC (P = .011). Dorsal attention network strength correlated with severity of dependence for cannabis (ρ = 0.215, P = .04).

Conclusion

We demonstrate specific cannabis and patient effects in networks associated with visual attentional processing. There is a differential association with hallucinatory symptoms in patients with and without a history of cannabis use. This may indicate that dysconnectivity in these networks serves different roles in the context of cannabis use.
Exploring the effects of Ia reciprocal inhibition on neuromodulatory commands in the human lower limb
Authors: Pearcey Gregory E. P. , Khurram Obaid U. , Beauchamp James A. , Heckman Charles J.
Published: April 2020

The control of normal motor behaviors involves sublime interactions between excitatory, inhibitory and neuromodulatory commands to motoneurons. The effects of altered inhibition on neuromodulatory commands has not received much attention in humans. Yet, motoneuron firing patterns can be readily measured from the muscle fibers they innervate, collectively known as motor units (MUs), due to their one‐to‐one spike ratio. Persistent inward currents (PICs) are reduced with activation of Ia fibers from the antagonist muscle in the decerebrate cat. Here, we set out to explore whether estimated PICs are affected by a tonic vibratory input to antagonist tendons in humans. MU firing patterns of the tibialis anterior (TA), soleus (SOL) and medial gastrocnemius (MG) were discriminated using high‐density surface electromyography array electrodes and a convolutive blind source separation algorithm. PICs were estimated using the paired MU analysis technique, which quantifies discharge rate hysteresis (ΔF) by comparing the onset and offset of a high‐threshold MU with respect to a low‐threshold MU, providing an estimate of neuromodulatory drive to the MU. Participants performed isometric plantarflexion and dorsiflexion triangular ramp contractions to 30% of maximal voluntary contraction with 10 s ascending and descending phases. In half of the trials, we applied vibration (128 Hz) to the distal TA tendon (plantarflexion) or Achilles tendon (dorsiflexion) with a constant force of 15 ± 2 N. There were large decreases in ΔF for both the SOL (31.3 ± 7.94%, p = 0.006, d = 0.81) and MG (31.4 ± 10.36%, p = 0.008, d = 0.9) during plantarflexion contractions with vibration applied to the distal TA tendon, and there was a moderate decrease in ΔF for the TA (10.9 ± 8.79%, p = 0.009, d = 0.63) during dorsiflexion with vibration to the Achilles tendon. These findings suggest that Ia reciprocal inhibition from the antagonist muscle can reduce the discharge rate hysteresis, providing insights about the interactions that occur to produce normal human motor behaviors.

Support or Funding Information

This work was supported by National Institute of Health (NIH) grants R01NS098509‐01 and T32HD007418‐23, and a Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellowship.
Vascular Phenotype is Compromised in Dynamically Stiffening Hydrogel
Authors: Schnellmann Rahel , Wei Zhao , Choudhury Mohammad Ikbal , Sun Sean , Gerecht Sharon
Published: April 2020

Cardiovascular diseases are one of the leading causes of death worldwide with age mediated endothelial dysfunction as one of the major risk factors. Endothelial dysfunction is caused by a variety of reasons, such as oxidative stress, DNA damage and senescence. Although, observations in vivo showed a clear correlation between increased extracellular matrix (ECM) stiffness and morphological changes within the vasculature, the identification of underlying signaling pathways in endothelial cells remains challenging, due to the lack of physiological 3D systems. Here we report the use of a fibrillary hydrogel, composed of hyaluronic acid and collagen I, which is capable of dynamically changing its stiffness along cell culture. This hydrogel allows for the increase in stiffness after the development of a mature vascular network, therefore mimicking the natural process of aging ex vivo. Using this system we found that an increase in ECM stiffness leads to a decrease in vessel length, increase in lumen size and the disassembly of adherence junctions. We further observed that an increase in matrix stiffness leads to changes in cell contractility and pFAK signaling, leading to further increase in matrix stiffness and the disassembly of adherence junctions. Inhibition of cell contractility using blebbistatin partially rescues the vascular morphology and the integrity of adherence junctions.

Support or Funding Information

Maryland Stem Cell Fund (RS is MSCRF Fellow)
The Impact of Perinatal Exposure to Inflammation and Hyperoxia on the MicroRNA Profile of the Developing Heart
Authors: Pavlek Leeann , Korada Roopi , Rogers Lynette
Published: April 2020

Background

Several cardiac‐specific microRNAs (miRs) are involved in the embryonic and postnatal development of the heart, with alterations in normal expression implicated in multiple disease states. This research aims to understand the impact of exposure to maternal systemic inflammation and/or postnatal hyperoxia on the microRNA profile of the developing heart using a murine model. MiRs‐1 and ‐133 are involved early in cardiac embryogenesis and regulate the transformation of mesoderm into cardiomyocytes. MiR‐195 regulates the cell cycle and proliferation of cardiomyocytes. MiRs‐208a, ‐208b, and ‐499 regulate the differential expression of myosin heavy chain isoforms, which contribute to myocardial contractile strength and energy consumption.

Methods

Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) intraperitoneal lipopolysaccharide (LPS) to induce maternal inflammation or saline. Offspring were euthanized on E18 or postnatal day 1 (P1). Other offspring were placed into room air or 85% oxygen for 7 days after birth before euthanizing on P7. RT‐PCR was used to analyze expression of microRNA‐1, ‐133, ‐195, ‐208a, ‐208b, and ‐499. Results were normalized to expression of U6.

Results

At E18 with exposure to LPS, no differences in expression were detected for miR‐1, ‐ 133, ‐195, ‐208, or 499. Exposure to LPS at P1 led to upregulation of miR‐208a (3‐fold; p=0.032) and miR‐208b (10‐fold; p=0.032), but no differences in expression of miR‐1, ‐133, ‐ 195, or ‐499. Upregulation of miR‐208a (4‐fold; p=0.006) and miR‐208b (7‐fold; p=0.047) persisted in hearts exposed to LPS/O2 at P7. No changes in expression of miR‐1, ‐133, ‐195, or ‐ 499 were detected in samples exposed to LPS and/or hyperoxia at P7.

Conclusions

Perinatal exposure to inflammation and hyperoxia led to upregulation of miR‐208a and miR‐208b expression in heart tissue from samples at P1 and P7. No changes in expression of miR‐208a and ‐208b were detected in embryonic heart samples. Perinatal exposure to inflammation and hyperoxia did not alter expression of miR‐1, ‐133, ‐195, or ‐499 at any timepoint.

Support or Funding Information

American Academy of Pediatrics Marshall Klaus Perinatal Research Award (Pavlek)
The Effects of Chemotherapeutic Agents and a Mitochondrial Antioxidant on the Brain Transcriptome and Cognitive Function
Authors: Cavalier Alyssa N. , Clayton Zachary , Wahl Devin , Seals Douglas , LaRocca Thomas
Published: April 2020

Cancer is the second leading cause of death in the United States, and over one‐third of patients will receive chemotherapy. One of most frequently reported side effects of chemotherapy is decreased cognitive function, commonly known as “chemobrain.” The underlying biological mechanisms of chemobrain are unclear, but could involve mitochondrial dysfunction and oxidative stress, which have been implicated in peripheral tissues, and could therefore be a therapeutic target. To investigate this possibility in the brain, we measured cognitive function and transcriptome changes by RNA‐seq in mice treated with doxorubicin, a common chemotherapy agent (single intraperitoneal injection, 10mg/kg, at 4 months old), or with doxorubicin plus the mitochondrial antioxidant, MitoQ (250 μM in drinking water for 4 weeks). We observed marked behavioral differences in doxorubicin‐treated mice, such as decreased overall exploration time in the novel object recognition test (NOR, an index of learning/memory). Despite these differences, we observed a trend towards reduced learning/memory (NOR) with doxorubicin treatment compared to sham. MitoQ did not prevent this; however, in RNA‐seq data, we found that doxorubicin increased expression of 127 genes and decreased expression of 154 genes (p < 0.01 vs. sham). These genes corresponded to ~80 transcriptional modules (FDR < 0.01), which were enriched for gene ontology terms related to synaptic transmission/plasticity, learning/memory, neurogenesis and neurotransmitter processing. MitoQ prevented most of these transcriptome changes (31 upregulated and 101 downregulated genes, p < 0.01 vs. sham) which corresponded to expression of only 16 transcriptional modules (none specifically related to brain function). Thus, our results suggest that MitoQ may have potential as a treatment for chemobrain at the biological level; however, its effects on brain/cognitive function require further investigation.

Support or Funding Information

AG060302
Characterization of MC903 induced Atopic Dermatitis‐like skin inflammation in mice
Authors: Chu Katharine , Su Zhi , Wetter Joseph , Namovic Marian , Leys Laura , Wang Yibing , Honore Prisca , McGaraughty Steve
Published: April 2020

Atopic Dermatitis (AD) is a chronic inflammatory skin disease that affects both adults and children worldwide. Symptoms of AD, such as recurrent dry, scaly lesions and intensive pruritus, can become an enormous burden to patients and their caregivers. Animal models are needed to better understand the pathophysiology of AD and for evaluating novel therapeutics. Topically applying MC903 (calcipotriol) on mouse skin has been reported to capture key features associated with AD. In the current study, we conducted a comprehensive characterization of MC903 induced ear skin inflammation in the mouse. An 11 day time course revealed skin thickening starting as early as day 4 and significantly progressing up to day 10. This chronicity was mirrored by increased transepidermal water loss in the ear skin. Histologically, hypervascularization, spongiosis, strong immune cell infiltration and epidermal hyperplasia were observed. The animals also manifested pruritic behaviors. The skin expression of Type 2 and other inflammatory cytokines such as IL‐4, IL‐5, IL‐31, TSLP (peak day 4), IL‐1β, IFNγ, TNFα were typically elevated by day 7 and further increased to day 10. Most of these endpoints were attenuated by administration of a selective JAK1 inhibitor (ABT‐317) or a steroid (Dexamethasone). The observations further the understanding of the utility of MC903 as a preclinical model for AD.

Support or Funding Information

Disclosures: All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.