Background Early non-response to biologic therapy has been shown to be associated with a low probability of long-term response in rheumatoid arthritis1 and psoriasis.2 However, to date there is a shortage of data regarding early identification of non-responders in psoriatic arthritis (PsA). Such analyses may help avoid unnecessary exposure, increase cost-effectiveness and improve the chance of achieving long-term treatment goals.
Objectives To assess the association between disease activity (DA) and clinical response (CR) during the first 12 weeks (wks) of treatment, and attainment or lack of attainment of a treatment target at Wk48 in PsA patients (pts) receiving certolizumab pegol (CZP).
Methods The relationship between DA state, CR or a combination of both during the first 12 wks of treatment, and Minimal Disease Activity (minDA)3 or DAS28 (CRP) remission at Wk48 was assessed post hoc using data from the RAPID-PsA trial (NCT01087788).4 DA state was defined using DAS28 disease activity thresholds for DAS28 (ESR) (not validated for DAS28[CRP]): DAS28 remission (<2.6), low (LDA) (≥2.6, ≤3.2), moderate (MDA) (>3.2, ≤5.1) or high (HDA) (>5.1). CR level was defined as improvement from baseline in DAS28 ≤0.6, 0.6–1.2, and >1.2. Descriptive analyses are based on all pts randomized to CZP (200mg Q2W and 400mg Q4W doses combined). Predictability analyses for a given wk are based on all pts continuing treatment at that wk. For these pts, last observation carried forward and non-responder imputation were applied to DAS28 and minDA, respectively, for withdrawals before, or missing evaluation at, Wk48.
Results A clear relationship between DA state at Wk2 and minDA at Wk48 was observed, with 68% (17/25) of pts in remission at Wk2 achieving minDA at Wk48, compared with 10% (5/52) of pts with HDA at Wk2 achieving minDA at Wk48. This trend was maintained at Wk12, by which point more pts had LDA and remission, and fewer pts had MDA and HDA. 73% (57/78) of pts in remission at Wk12 achieved minDA at Wk48, and 0% (0/26) of pts with HDA at Wk12 achieved minDA at Wk48 (Table A). When DAS28 remission – a less stringent target that excludes enthesitis and skin manifestations – was used, a similar trend was observed, but more pts in LDA, MDA or HDA at each time point achieved the target; however, still only 4% (1/26) of pts with HDA at Wk12 attained remission at Wk48 (Table B). CR level at Wk12 was also associated with likelihood of attaining minDA at Wk48 (albeit to a lesser extent): Of 153/256 (60%) CZP pts that achieved DAS28 CR >1.2 at Wk12, 50% (76/153) achieved minDA at Wk48, while 12% (6/50) of non-responders at Wk12 (pts with DAS28 CFB ≤0.6) achieved minDA at Wk48.
Conclusions Using DA state and CR level at an early stage of CZP treatment, it was possible to identify pts with PsA who are unlikely to achieve long-term treatment goals. This approach may enable physicians adopting a treat-to-target strategy to determine early on when to change therapy in pts not responding to CZP.
van der Heijde D. J Rheum 2012;39(7):1326-1333.
Zhu B. Br J Dermatol 2013;169(6):1337-1341.
Coates L.C. Ann Rheum 2010;69(1):48-53.
Mease P.J. Ann Rheum Dis 2014;73(1):48-55.
Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.
Disclosure of Interest P. Mease Grant/research support: (Abbott) AbbVie, Amgen, BiogenIdec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Vertex, Consultant for: (Abbott) AbbVie, Amgen, BiogenIdec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB Pharma, Vertex, Speakers bureau: (Abbott) AbbVie, Amgen, BiogenIdec, BMS, Crescendo, Genentech, Janssen, Lilly, Pfizer, UCB Pharma, R. Fleischmann Grant/research support: Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, MSD, Novartis, BiogenIdec, Astellas, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Novartis, Astellas, AstraZeneca, Janssen, O. Davies Shareholder of: UCB Pharma, Employee of: UCB Pharma, T. Nurminen Employee of: UCB Pharma, D. van der Heijde Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma
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