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Abstract
Background Several trials studied initiation of therapy in early RA patients with a more intensive strategy than the standard disease modifying anti-rheumatic drug (DMARD) strategy according to current guidelines, with the aim of rapidly inducing clinical remission (remission-induction strategies).
Objectives To establish in early RA patients the effectiveness of remission-induction strategies compared to standard DMARD strategies according to current guidelines.
Methods A systematic literature review was performed, searching Embase and Medline October 2018 for RCTs and other comparative studies in early RA patients, published the past 5 years. Induction therapy was defined as initiating treatment with a biological (b)DMARD or a targeted small molecule (ts)DMARD, both with or without a conventional synthetic (cs)DMARD, or initiating a csDMARD with moderately-high dosed glucocorticoids (GCs), with delayed tapering (not ‘bridging therapy’) or starting ≥2 csDMARDs. Standard DMARD strategy was defined as starting monotherapy with a csDMARD, with or without GCs as bridging therapy.
The outcome was remission according to a validated disease activity index or the Boolean definition.1 Numbers of patients were extracted from all studies and relative risks (RR) for achieving remission with 95% confidence intervals (95%CI) per study were calculated. Subgroup analyses were performed for different definitions of remission, the use of a b/tsDMARD as part of the induction therapy strategy (yes/no) and the use of concomitant GC bridging therapy (yes/no) in standard DMARD strategies.
Results Included were 22 clinical studies, involving 4435 patients in induction strategies and 3314 in standard DMARD strategies. For remission, 17 studies applied the criterion of DAS28 <2.6, 12 the Boolean remission definition, 7 CDAI ≤2.8 and 10 studies SDAI ≤3.3. Remission had to be present during 6 to 12 months in all studies. Heterogeneity in study design prohibited providing an overall pooled effect estimate, but for subgroups pooled estimates were given for descriptive purposes.
In the figure we provide results for studies applying the DAS28 remission definition. Of those studies, 13/17 (76%) showed a statistically significant effect in favour of induction therapy. The pooled RR of achieving remission for strategies initiating bDMARDs was 1.73 [95%CI 1.59 to 1.88] versus the standard DMARD strategy without GC bridging, and it was 1.20 [95%CI 1.03 to 1.40] for induction strategies without bDMARD versus standard DMARD strategies without GC bridging. No superior effect of any induction strategy was found compared to that of standard DMARD strategies with GC bridging (pooled RR 1.06, 95%CI 0.83 to 1.35).
When using other remission definitions, all induction strategy studies with Boolean/CDAI/SDAI outcomes applied a b/tsDMARD, and 63%, 100% and 78%, respectively found a statistically significantly superior effect compared to standard DMARD strategies without GC bridging; however, compared to standard DMARD strategies with GC bridging, only trends in the same direction were found.
Conclusion Induction therapy strategies initiated in early RA patients are more effective in achieving remission compared to standard DMARD strategies. However, their benefit compared to that of a standard DMARD strategy with GC bridging seems to be limited.
References [1] Felson DT, et al. Arthritis Res Ther. 2011;63;573-586
Disclosure of Interests Maxime Verhoeven: None declared, Paco Welsing: None declared, Johannes WJ Bijlsma Grant/research support from: The department of the author who included patients (JWJB) in the U-Act-Early trial received reimbursements from Roche Nederland BV. JWJB reported grants and fees from Roche, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, and UCB
University Medical Center Utrecht, Utrecht University, Consultant for: SUN Pharma, Speakers bureau: Lilly, Roche, Jacob M. van Laar Grant/research support from: Genentech, Consultant for: F. Hoffmann-La Roche, Floris Lafeber Shareholder of: ArthroSave, Grant/research support from: FOREUM; Dutch Arthritis Society, Janneke Tekstra: None declared, Johannes W. G. Jacobs Grant/research support from: Roche, Consultant for: Roche