Clinical trial NCT04614311: Strategies Towards Personalised Treatment in Juvenile Idiopathic Arthritis (JIA).
Official title: Strategies Towards Personalised Treatment in Juvenile Idiopathic Arthritis (JIA): the MyJIA Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: The Research Council of Norway
name: Haukeland University Hospital
name: St. Olavs Hospital
name: University Hospital of North Norway
name: Helse Stavanger HF
First posted: 2020-11-03
Enrollment: 189
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel intervention were participants are assigned to either the control group or intervention group.
Primary purpose: TREATMENT

Brief summary: Inhibitors of tumour necrosis factor (TNFa) reduce inflammation in patients with juvenile idiopathic arthritis (JIA), but only 20-40 percent achieve a state of no or very little disease activity. Tailored glucocorticoid joint injections are widely used (usually in general anaesthesia), but no controlled studies have addressed the effect of this approach. In Norway there are unique possibilities for early interventions, rapid escalation of medication and individualised therapy. The investigators aim to find the optimal ways to increase disease control and improve quality of life for JIA patients.

The hypothesis is that JIA patients starting TNF-inhibitors with added steroid injection of inflamed joints, will lead to improved outcomes compared to TNF-inhibitors with no joint injections, and that therapeutic drug monitoring, modern imaging and biologic and clinical profiling can be utilised to characterise JIA patients with different anti-TNF responses.

MyJIA is a national investigator initiated 48 weeks RCT of JIA patients starting TNF-inhibitors; 202 JIA patients will be randomised at baseline to A) concomitant intra-articular glucocorticoid injections versus B) no injections. Primary endpoint is the rate of sustained remission from weeks 24 to 36. Possible risk factors for not reaching remission will be analysed including clinical characteristics, drug antibodies/serum concentrations, patients' reported health status and preferences, molecular signalling (based on transcriptional, cellular and genetic risk) and synovitis detected by modern imaging (ultrasound and whole-body MRI).

Patients will be recruited from all Norwegian health regions through an established collaboration. Unit of Paediatric Rheumatology, Oslo University Hospital, with an extensive research track in this field, will be the coordinating centre. Broad research cooperation across disciplines is established. The trial is highly innovative in evaluating treatment options and strategies to individualise and optimise the efficacy and safety of JIA treatment.


Eligibility criteria: Inclusion Criteria:

1. 1-18 years of age at the time of signing the informed consent.
2. Fulfilment of the International League of Associations for Rheumatology (ILAR) classification criteria for non-systemic JIA.
3. Clinical indication for starting TNFi treatment according to consensus between at least two physicians.
4. Naïve to TNFi or prior use of one TNFi (stopped at least 3 months before study inclusion and no previous TNFi treatment failure).
5. Juvenile Disease Activity Score (JADAS) \>1 at baseline and at least one joint with active arthritis were joint injection is considered.
6. Willing to give written consent (participant ≥ 16, guardians if \< 16 years of age, both participants and guardians if 16-18) and comply with the requirements of the study protocol.

Exclusion Criteria:

Medical Conditions

1. Major comorbidity including uncontrolled infectious, neurological or mental disease, malignant disease, severe heart failure, severe renal failure, active ulcus ventriculi, and uncontrolled diabetes mellitus.

   Prior/Concomitant Therapy
2. Used two or more TNFi.
3. Corticosteroid use (including i.a. injection) less than 4 weeks prior to randomisation.

   Other Exclusions
4. Known hypersensitivity to Triamcinolone hexacetonide (Lederspan) or any of the excipients (sorbitol, polysorbate or benzyl alcohol).
5. Concomitant therapy with CYP3A-inhibitors or digitalis glycosides.
6. Known inherited fructose intolerance
7. Presence of hepatitis B surface antigen (HBsAg) at screening.
8. Positive hepatitis C antibody test result at screening or within 12 months prior to starting study treatment.
9. Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (front), and TB testing. The choice of TB tests will be made by the investigator according to local licensing and standard of care.
10. Having received live vaccines less than two weeks prior to randomisation.
11. Drug / alcohol abuse which hampers adherence to the study protocol.
12. Language barriers that hampers adherence to the study protocol.
13. Pregnancy or breast-feeding.

Primary outcomes:
measure: The proportion of JIA participants with sustained inactive disease
timeFrame: Week 24 to week 36.
Secondary outcomes:
measure: The proportion of participants with ACR pedi 30% response
timeFrame: Baseline to week 6,12 and 24
measure: The proportion of participants with ACR pedi 50,70 and 90% response
timeFrame: Baseline to week 6, 12 and 24.
measure: Juvenile arthritis disease activity score (JADAS)
timeFrame: Baseline to week 6, 12 and 24.
measure: Time to inactive disease
timeFrame: Baseline to 48 weeks
measure: Proportion of Participants with Minimal Disease Activity
timeFrame: Week 26 to 48
measure: Change from baseline in arthritis-related pain severity as measured by pain VAS item
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Trondheim
country: Norway
facility: St Olavs Hospital
state: Trønderlag
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North Norway
Study officials:
affiliation: Oslo University Hospital
name: Pernille H Bøyesen, MD PhD
role: STUDY_DIRECTOR
affiliation: Oslo University Hospital
name: Anna-Birgitte Aga, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital
name: Berit Flatø, Prof
role: PRINCIPAL_INVESTIGATOR
References: