Objectives New drugs have become available in PsA. As part of the update of the EULAR recommendations for the management of PsA, we performed a systematic literature review to assess the efficacy and safety of pharmacological agents for the management of patients with PsA.
Methods Randomised controlled trials (RCTs), including long-term extensions, comparing any two pharmacological interventions for the management of patients with PsA, were identified by searches in Medline, Embase and Cochrane datasets (2010-2014), supplemented by searches in 2013-2014 EULAR and ACR abstracts. Pharmacological interventions were defined as any biological (bDMARD), synthetic DMARD (sDMARD) either conventional or targeted, NSAID, glucocorticoid or any combination and they could be compared to any of them, placebo (PBO) or no treatment. Strategy trials were also included. The main efficacy outcomes were ACR20, ACR50, PASI75 and radiographic progression, and the main safety outcome was withdrawals due to adverse events. Risk of bias (RoB) was assessed according to the Cochrane tool. Multiple studies of the same intervention were meta-analysed with random effects analysis in RevMan.
Results Of 2,278 articles and 387 conference abstracts screened, 42 (24 papers and 18 abstracts) met the inclusion criteria. A total of 19 articles/abstracts focused on 3 new drugs for the management of PsA: ustekinumab (UST), apremilast (APR) and secukinumab (SEC). All were PBO-compared trials and met their primary endpoint, ACR20; RoB was low (UST, SEC) or unclear (APR). For achieving ACR20, absolute responses are in the Table. Risk ratios (RR) versus PBO were respectively for UST90mg and UST45mg of 2.17 (95%CI 1.71-2.76) and 1.95 (1.52-2.50); for APR30mg and APR20mg of 2.06 (1.67, 2.54) and 1.84 (1.51-2.25); and for SEC300mg, SEC150mgand SEC75mg, of 3.31 (2.04-5.36) 5.82 (1.56-21.71) and 4.47 (0.66-30.26). For all these drugs, there were no more withdrawals due to AEs in the active treatment arms compared to PBO. The 3 drugs showed efficacy on dactylitis and enthesitis, with APR apparently showing less pronounced effects. Eleven articles/abstracts on golimumab and certolizumab pegol demonstrated the efficacy and safety of these drugs with respect to all outcomes. A strategy trial, TICOPA, has shown better ACR responses with tight control compared to standard care; patients under tight control had a higher incidence of adverse events (no unexpected adverse events). No studies were found on NSAIDs or glucocorticoids.
Conclusions UST, APR and SEC are new drugs with efficacy demonstrated for the treatment of PsA. No major safety signals arise, but long-term studies are needed. Studies with new TNFi confirm the efficacy of these drugs. This review informs the update of the EULAR recommendations for the management of PsA.
Disclosure of Interest S. Ramiro: None declared, J. Smolen Consultant for: AbbVie Inc., Amgen, AstraZeneca, Astro, BMS, Celgene, Centocor-Janssen, Glaxo, Lilly, Pfizer, MSD, Novo-Nordisk, Roche, Samsung, Sandoz, and UCB, R. Landewé Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB, Vertex Director of Imaging Rheumatology b, D. van der Heijde Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB, Vertex Director of Imaging Rheumatology b, M. Dougados Consultant for: AbbVie, Pfizer, UCB, Novartis, Sanofi, Lilly, Merck, BMS, P. Emery Consultant for: Abbvie, Pfizer, MSD, UCB, Roche, Novartis, BMS, M. de Wit Consultant for: AbbVie, BMS, Celgene, Eli-Lilly, Novartis, Roche, M. Cutolo Consultant for: BMS, Actelion, Celgene, Celltrion, Horizon, Mundipharm, S. Oliver Consultant for: AbbVie, MSD, Pfizer, Regeneron, Roche and UCB, L. Gossec Consultant for: Abbvie, Amgen, Celgene, Chugai, Janssen, MSD, Novartis, Pfizer, Regeneron, Roche and UCB.