Background C-EARLY (NCT01519791) assessed the efficacy and safety of certolizumab pegol (CZP)+optimized MTX vs placebo (PBO)+optimized MTX in inducing and maintaining a sustained clinical response, and inhibiting radiographic damage, in DMARD-naïve patients (pts) with active, severe, progressive RA.1 Here, we examine the association between an inadequate response to PBO+MTX or CZP+MTX treatments at Week (Wk) 12 (lack of improvement from baseline [BL] in DAS28[ESR], DAS28[CRP] or CDAI) and corresponding response at Wk 52.
Objectives To examine the association between Wk12 response and Wk52 clinical response (remission [REM]/low disease activity [LDA]) in recently diagnosed DMARD-naïve pts with active, severe, progressive RA, treated with CZP+optimized MTX vs PBO+optimized MTX.
Methods This multicenter, double-blind, randomized controlled trial enrolled pts who were DMARD-naïve with active, severe, progressive RA (<1yr since diagnosis, fulfilling 2010 ACR/EULAR criteria). 879 pts were randomized 3:1 to CZP (200mg Q2W+MTX; n=660) or PBO Q2W+MTX (n=219). MTX was initiated at 10mg/wk and increased to 25mg/wk by Wk8; maximum tolerated dose per pt (mean optimized dose, CZP: 21mg/wk, PBO: 22mg/wk) was maintained to Wk52. Negative predictive values (NPV) were defined as probability of failing to achieve Wk52 REM (DAS28[ESR]/[CRP]<2.6 or CDAI≤2.8) or LDA (DAS28[ESR]/[CRP]≤3.2 or CDAI≤10) after failing to achieve a corresponding defined response at Wk12; change from BL in DAS28(ESR)/(CRP)≥0.6 or ≥1.2/CDAI≥6 and ≥12. DAS28(CRP) LDA/REM definitions are not validated. Observed data were utilized for Wk12 responses; missing Wk52 values were imputed using non-responder imputation.
Results The NPV of Wk12 responses were high (Table): PBO+MTX pts who did not achieve DAS28(ESR) improvements from BL ≥0.6 had 94% probability of not being in REM or LDA at Wk52. CZP+MTX pts who did not achieve DAS28(ESR) improvements from BL ≥1.2 had 93% probability of not being in REM at Wk52. NPV of changes in DAS28(CRP) and CDAI at Wk12 were less informative for predicting remission at 1yr (Table).
Conclusions In early RA pts treated with optimized-dose MTX, failure to achieve a ≥0.6 DAS28(ESR) reduction from BL at Wk12 was associated with a low probability (6%) of DAS28(ESR) REM/LDA at Wk52, supporting treatment step-up at 3 months. For pts with active, severe RA with poor prognostic factors where CZP has been initiated as first-line treatment, failure to achieve a rapid decrease of 1.2 points was associated with a reduced likelihood of achieving REM (7%). These findings in DMARD-naïve pts are consistent with the negative predictability outcomes for CZP in established RA.2
Weinblatt M. Arthritis Rheumatol 2015;67(S10);
van der Heijde D. J Rheumatol 2012;39:1326–33
Acknowledgement The authors acknowledge Costello Medical Consulting, funded by UCB Pharma, for writing and editorial assistance.
Disclosure of Interest X. Mariette Grant/research support from: Pfizer and GlaxoSmithKline., Consultant for: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, UCB Pharma and Sanofi-Aventis, C. Bingham Consultant for: UCB Pharma, G.-R. Burmester Consultant for: AbbVie, MSD, Pfizer, Roche and UCB Pharma, V. Bykerk: None declared, P. Emery Consultant for: Bristol-Myers Squibb, Pfizer, MSD, AbbVie, UCB Pharma, Roche, Schering Plough, Novartis and Samsung, D. Furst Grant/research support from: Abbott, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma, Consultant for: Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen IDEC, Janssen, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex, Employee of: Director of Imaging at Rheumatology BV, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB Pharma, Consultant for: AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB Pharma, Vertex, B. VanLunen Employee of: UCB Pharma, C. Arendt Employee of: UCB Pharma, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience and UCB Pharma, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Lilly, MedImmune, Merck, Novartis, Pfizer, Roche and UCB Pharma
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