Background/Purpose: Early non-response to biologic therapy has been shown to be associated with a low probability of long-term response in rheumatoid arthritis¹ and psoriasis². 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. Here we aim to assess the association between disease activity (DA) and clinical response (CR) during the first 12 weeks (wks) of treatment, and attainment/lack of attainment of treatment targets at Wk48 in PsA patients (pts) receiving certolizumab pegol (CZP).

Methods: The relationship between DA state during the first 12 wks of treatment, and Minimal Disease Activity (minDA)³ or DAS28(CRP) <2.6 at Wk48 was assessed post hoc using data from the RAPID-PsA study (NCT01087788).⁴ DA state was defined using either DAS28(CRP) values: <2.6, 2.6–3.2, 3.2–5.1, >5.1; or PsARC response/non-response. Descriptive analyses are based on all pts randomized to CZP from Wk0. Pts that discontinued treatment during the first 12 wks were excluded from the analysis. For remaining pts, missing data were imputed using LOCF for DAS28 and PsARC, and NRI for minDA.

Results: A relationship between Wk2 DA state and Wk48 minDA was observed, with 68% (17/25) of pts with DAS28(CRP) <2.6 at Wk2 achieving Wk48 minDA, compared with 10% (5/52) of pts with Wk2 DAS28(CRP) >5.1. This trend was maintained at Wk12, by which point more pts had lower DA. 73% (57/78) of pts with Wk12 DAS28(CRP) <2.6 achieved Wk48 minDA, compared to 0% (0/26) of pts with Wk12 DAS28(CRP) >5.1 (Table A). When Wk48 DAS28(CRP) <2.6 – a less stringent target that excludes enthesitis and skin manifestations – was used, a similar trend was observed, but more pts in each category achieved the target; however, still only 4% (1/26) of pts with Wk12 DAS28(CRP) >5.1 attained Wk48 DAS28(CRP) <2.6 (Table B). CR at Wk12 was also associated with likelihood of attaining minDA at Wk48: Of 153/256 (60%) CZP pts that achieved Wk12 DAS28(CRP) CR >1.2, 50% (76/153) achieved Wk48 minDA, compared to 32% (17/53) of pts with Wk12 DAS28(CRP) CR 0.6–1.2 and 12% (6/50) of Wk12 non-responders (DAS28[CRP] CR ≤0.6). PsARC response at Wk12 was also associated with Wk48 outcomes: 10.7% (6/56) of Wk12 PsARC non-responders achieved Wk48 minDA, compared to 47.7% (95/199) of Wk12 PsARC responders.

Conclusion: Using DA state and CR level at an early stage of CZP treatment, it was possible to identify PsA pts 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.

References:

1. van der Heijde D. J Rheum 2012;39(7):1326–1333

2. Zhu B. Br J Dermatol 2013;169(6):1337–1341

3. Coates L.C. Ann Rheum 2010;69(1):48–53

4. Mease P.J. Ann Rheum Dis 2014;73(1):48–55