Trial reportAnnals of the rheumatic diseases2023
Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2).
Trial report in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study, Comparing GSK3196165 With Placebo and With Tofacitinib in Combination With Conventional Synthetic DMARDs, in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic DMARDs or Biologic DMARDs
A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study Comparing GSK3196165 With Placebo and With Tofacitinib, in Combination With Methotrexate in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Therapeutic approaches for difficult-to-treat rheumatoid arthritis: a systematic literature review of current evidence.RMD open · 2026Pooled it
- Pooled it
- Trial
- Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis.Arthritis research & therapy · 2024Trial
- Microfluidic-based biomimetic mitochondrial nanocomposite for targeted immunotherapy of rheumatoid arthritis via mitochondrial transplantation.Materials today. Bio · 2026Article
- Mechanistic impasses: tofacitinib treatment ameliorates GM-CSF-driven macrophage inflammation.Cellular & molecular immunology · 2026Article
- A Focused Comparative Review of Innovative Therapeutics Across Autoimmune and Chronic Inflammatory Diseases.Life (Basel, Switzerland) · 2026Review
- Tofacitinib repairs inflammation and mitochondrial dysregulation in GM-CSF-reprogrammed RA macrophages.Cellular & molecular immunology · 2026Article
- GM-CSF promotes pro-inflammatory macrophage activation associated with Akt/mTOR signaling during experimental colitis.Frontiers in immunology · 2026Article
- Failed resolution as a mechanistic basis of difficult-to-treat rheumatoid arthritis: stromal-myeloid crosstalk in the synovium and emerging resolution-restoring therapies.Frontiers in immunology · 2026Review
- Targeting GM-CSF in Rheumatoid Arthritis: Advances in Cytokine-Directed Immunotherapy and Clinical Implications.Life (Basel, Switzerland) · 2025Review
- Article
- Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer.Cancer science · 2025Article
- Promising Molecular Therapeutic Targets for Drug Development in Rheumatoid Arthritis.Journal of clinical medicine · 2025Review
- Targeting the double-edged sword: cytokines in the pathogenesis and treatment of autoimmune diseases.Inflammopharmacology · 2025Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Anti-GM-CSF autoantibodies in myeloid leukemias.Best practice & research. Clinical haematology · 2025Review
- GM-CSFTheranostics · 2025Review
- Modulating M1/M2 macrophage polarization with plant metabolites: a therapeutic strategy for rheumatoid arthritis.Frontiers in pharmacology · 2025Review
- Updating the 2019 ACR/SAA/SPARTAN Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis (SPARTAN 2024 Annual Meeting Proceedings).Current rheumatology reports · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.
methodsTwo phase 3, double-blind randomised controlled trials including patients with inadequate responses to methotrexate (contRAst 1) or conventional synthetic/biologic disease-modifying antirheumatic drugs (cs/bDMARDs; contRAst 2). Patients received background csDMARDs. Through a testing hierarchy, subcutaneous otilimab (90/150 mg once weekly) was compared with placebo for week 12 endpoints (after which, patients receiving placebo switched to active interventions) or oral tofacitinib (5 mg two times per day) for week 24 endpoints. PRIMARY ENDPOINT: proportion of patients achieving an American College of Rheumatology response ≥20% (ACR20) at week 12.
resultsThe intention-to-treat populations comprised 1537 (contRAst 1) and 1625 (contRAst 2) patients. PRIMARY ENDPOINT: proportions of ACR20 responders were statistically significantly greater with otilimab 90 mg and 150 mg vs placebo in contRAst 1 (54.7% (p=0.0023) and 50.9% (p=0.0362) vs 41.7%) and contRAst 2 (54.9% (p<0.0001) and 54.5% (p<0.0001) vs 32.5%). Secondary endpoints: in both trials, compared with placebo, otilimab increased the proportion of Clinical Disease Activity Index (CDAI) low disease activity (LDA) responders (not significant for otilimab 150 mg in contRAst 1), and reduced Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Benefits with tofacitinib were consistently greater than with otilimab across multiple endpoints. Safety outcomes were similar across treatment groups.
conclusionsAlthough otilimab demonstrated superiority to placebo in ACR20, CDAI LDA and HAQ-DI, improved symptoms, and had an acceptable safety profile, it was inferior to tofacitinib. TRIAL REGISTRATION NUMBERS: NCT03980483, NCT03970837.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.