Stand UP to Rheumatoid Arthritis (SUPRA)
- Conditions
- Rheumatoid Arthritis
- Interventions
- Drug: Anti-IL6Drug: TNFiDrug: JAKi
- Registration Number
- NCT05305066
- Lead Sponsor
- Marie Hudson, MD
- Brief Summary
Rheumatoid arthritis is a disabling arthritis that affects young women disproportionately. Although the physicians have some excellent treatments, they do not know which treatment is best for which patient. The investigators want to find ways to identify the right drug for the right patient at the right time. This is what personalized medicine is all about.
- Detailed Description
Rheumatoid arthritis (RA) is a complex, chronic disease of the immune system characterized by disfiguring and disabling arthritis. It affects predominantly women (3:1 ratio with men) and has its peak onset during their most productive years (ages 30-50). RA is associated with serious morbidity (including impaired fertility and pregnancy outcomes, disability, and depression) and premature mortality (particularly from cardiovascular and infectious causes). The Arthritis Alliance of Canada estimates that the cost of RA will exceed $30 billion in Canada in 2040.
First-line treatment of RA consists of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with methotrexate considered as the gold standard. Yet, only 30% of patients will achieve adequate response to methotrexate and the majority will need additional treatment. The development of new biologic and targeted synthetic DMARDs (b/tsDMARDs) in the 20th century has transformed the treatment of RA. Anti-tumour necrosis factor (TNF)-α molecules were the first clinically successful biologic therapies for RA. Drugs targeting other signaling pathways (JAK-STAT, which work downstream of interferons), inflammatory cytokines (IL-6), as well as B cells and T cells have now also become available. Molecules with novel targets (eg. GM-CSF, CD40L) are in clinical trials.
Although hailed as 'game-changers' in patient care, the inconvenient truth is that even though nine different b/tsDMARDs are currently available to treat RA, 30% of patients will fail any particular drug. Moreover, physicians have no reliable way of predicting response and guiding treatment decisions. Clinical and genetic predictors have been the subject of intense research but these factors explain only a small portion of the observed variance in treatment response. Using the current trial-and-error approach, patients can cycle through multiple drugs before finally attaining disease control. This means months or years of suboptimal disease control and considerable losses in many domains including physical and emotional well-being, family and social networks, and occupational attainment. The lack of a personalized approach is particularly detrimental in RA because there is a narrow ''window of opportunity'' in the first 3-6 months of onset to control disease and optimize long term outcomes. In addition, failure to personalize treatment may also result in wasted spending on ineffective drugs, that cost up to $20,000 per patient per year, and exposing patients to unnecessary risks of adverse events, in particular serious infections.
There is a critical need to 1) transform the current 'trial-and-error' treatment paradigm, 2) explore novel predictors of b/tsDMARD response in RA and, 3) harness the power of advanced analytical strategies to personalize treatment decision-making and optimize outcomes in RA. The investigators propose a multi-pronged solution that combines innovative trial designs, multi-omics and advanced computational prediction to transform clinical care in RA.
The investigators propose to develop a new model of care and investigate new avenues, including sex and gender, diet, gut bacteria and environmental exposures, to make treatment decisions. The investigators will also use new methods of analyzing complex information. The highly talented research team has what is needed to transform the care of people living with RA.
In preparation for a full-scale study, the investigators propose this feasibility study.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
- Age ≥ 18 years;
- Arthritis that fulfills the 2010 ACR/EULAR classification criteria for RA;
- Failure to standard conventional synthetic DMARDs and eligible for second-line b/tsDMARDs (Sub-study 1) or failure to at least one TNF inhibitor and eligible for third-line b/tsDMARDs (Sub-study 2).
- Prior b/tsDMARDs for Sub-study 1 or prior b/tsDMARDs other than TNF inhibitors for Sub-study 2;
- Contraindication to b/tsDMARD therapy, such as active infection or untreated latent TB, current malignancy, severe organ dysfunction, history of VTE (unless anticoagulated), high risk of cardiovascular disease, pregnancy/lactation;
- Overlap with another inflammatory disease requiring specific immunosuppressive therapy, such as lupus nephritis;
- Unable to provide consent or complete forms (alone or with assistance) in English or French
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sub-study 1 Anti-IL6 Anti-IL6 Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab Sub-study 1 TNFi TNFi TNFi - any sub-cutaneous (sc) formulation, namely etanercept (receptor fusion protein), adalimumab (monoclonal antibody), golimumab (monoclonal antibody), or certolizumab (pegylated fragment of a monoclonal antibody) Sub-study 2 Anti-IL6 Anti-IL6 Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab Sub-study 2 JAKi JAKi JAKi - tofacitinib (JAK1/3 inhibitor), baricitinib (JAK 1/2 inhibitor) or upadacitinib (JAK1 inhibitor)
- Primary Outcome Measures
Name Time Method Proportion of eligible patients who accept to participate 12 months Patient acceptability outcome
Rate of recruitment at two RA referral centers over 12 months 12 months Feasibility outcome
Proportion of eligible patients who are invited to participate by their physician 12 months Physician acceptability outcome
Proportion of participants adhering to the allocated treatment 24 months Feasibility outcome
Prompt access to drugs 4 weeks Feasibility outcome
Proportion of patients reaching SDAI <= 3.3 24 months Exploratory outcome
Proportion of patients reaching DAS28 LDA state 24 months Exploratory outcome
Patient-reported outcomes (function, health-related quality of life, fatigue) 24 months Exploratory outcome
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Sir Mortimer B. Davis Jewish General Hospital
🇨🇦Montreal, Quebec, Canada