Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis

Abstract

ObjectivesTo update a previous systematic review assessing the efficacy of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA).MethodsTwo systematic reviews of the literature using PubMed, Embase and the Cochrane library were performed from 2009 until January 2013 to assess the efficacy of csDMARDs (as monotherapy or combination therapy) in adults with RA, and the efficacy of glucocorticoids in early RA. A third systematic review was performed until March 2013 to assess the efficacy of tofacitinib by meta-analysis.ResultsFor glucocorticoids, of 222 hits, five publications relating to four new trials were analysed for efficacy, confirming that initial treatment of RA with low-dose prednisone plus methotrexate (MTX) results in better clinical and structural outcomes at 1 and 2 years than treatment with MTX alone. For csDMARDs, of 498 studies, only two new studies were randomised controlled trials comparing MTX monotherapy with MTX in combination with another csDMARD without differences in glucocorticoid usage. Using tight control principles, clinical outcomes were no better with immediate triple therapy than with ‘step-up’ therapy. For tofacitinib, the pooled analysis of 10 trials showed that tofacitinib was more efficacious on signs and symptoms, disability and appeared to be more efficacious on structural damage than control treatment with placebo (OR (95% CI)—American College of Rheumatology 20% (ACR20) response: 2.44 (1.97 to 3.02)) or treatment with MTX (ACR20 response: 2.38 (1.66 to 3.43)).ConclusionsAddition of low-dose glucocorticoids to csDMARD therapy produces benefits in early RA. Under tight control conditions, combination therapy with csDMARDs is no better than MTX monotherapy. Tofacitinib is a new DMARD with proven efficacy.

Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

“…Several systematic reviews have concluded that low dose (B7.5 mg/day) GC can provide a useful ''bridgingtherapy'' below the therapeutic effects of the slower acting DMARDs start to manifest [60][61][62][63]. Conclusion accepted by EULAR in their 2010 recommendations [64] and further confirmed in 2014 [65]. The ACR has been rather more reticent on the use of GCs and in its 2012 update of recommendations, focussed on conventional DMARDs and biological therapies and did not address the use of GCs [66].…”

New Guidelines for the Management of Rheumatoid Arthritis (Eular, 2013): The Place of Glucocorticoids

“…Впоследствии в серии РПКИ [23][24][25][26][27][28][29][30], их метаанализе [32][33][34] и систематических обзо-рах [35,36] было доказано, что применение ГК (в комби-нации с БПВП) способствует более выраженному тормо-жению деструкции суставов по сравнению с монотерапи-ей БПВП, по крайней мере при раннем РА. При этом структурно-модифицирующий эффект ГК сохраняется в течение длительного времени после отмены ГК [37][38][39][40].…”

Eular Recommendations for the Treatment of Rheumatoid Arthritis – 2013: General Characteristics and Disputable Problems

“…МТ -эффективный («якорный») препарат для лече-ния РА, который применяется как в виде монотерапии, так в комбинации с ГК, стандартными БПВП и ГИБП [36,37]. Монотерапия МТ (в сочетании с ГК или без них) эффек-тивна у 30-60% пациентов [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56].…”