Background/Purpose: In the 12-week (wk) REALISTIC (RA EvALuation In Subjects receiving TNF Inhibitor Certolizumab pegol) (NCT00717236) Phase IIIb trial, certolizumab pegol (CZP) was associated with rapid and consistent clinical responses, reduced disease activity, and improved physical function in a diverse group of rheumatoid arthritis (RA) patients (pts) irrespective of concomitant or prior therapy or disease duration.1,2 We evaluated clinical responses in pts who completed the 12-wk double-blind (DB) phase and entered the open-label extension (OLE), up to Wk 28.
Method: Following the 12-wk DB phase (CZP 400 mg/placebo [PBO] at Wks 0, 2, 4, then CZP 200 mg/PBO at Wks 6, 8, 10 plus current treatment) pts received open-label CZP 200 mg every other week for ≥16 Wks. ACR responses, change from baseline (BL) in DAS28(CRP) and HAQ-DI, and DAS28(ESR) remission (DAS28 <2.6) at Wk 28 are shown in CZP and PBO Wk 12 completers receiving at least 1 dose of OL CZP at Wk 12 (OLE population). Pts who withdrew from the OLE for any reason had data imputed from that time point onward. For ACR responses, NRI and LOCF (from OLE visits only) were used for pts who withdrew due to AEs/lack or loss of efficacy and other reasons, respectively. Mixed model repeated measures (MMRM) was used for DAS28 and HAQ-DI. Safety data in DB phase and up to Wk 28 in OLE are presented.
Result: Of 851 CZP and 212 PBO pts in the ITT population, 771 (90.6%) and 184 (86.8%) completed the 12-wk DB phase and entered the OLE, respectively. BL disease characteristics and prior and concomitant therapy at randomization (Wk 0) were similar between CZP and PBO completers (Table). Percentage of pts with prior TNF inhibitor use was similar in OLE and DB phase (37.4% vs 37.6%, respectively). Clinical responses and improvements in DAS28 and HAQ-DI were comparable in CZP (28 wks CZP) and PBO (16 wks CZP) completers (Table). At Wk 28, DAS28(ESR) remission (DAS28<2.6) was achieved in 15.2% and 11.4% of CZP and PBO completers, respectively. CZP safety profile was similar to previous CZP trials. In the DB phase, incidence of AEs and serious AEs in CZP vs PBO groups was 522.05 and 26.68 vs 483.20 and 25.83 cases/100 pt-years, respectively; there were 2 deaths (1 case each of sigmoid diverticulitis and necrotizing pneumonia). In the OLE, incidence of AEs and serious AEs in CZP vs PBO completers was 239.12 and 13.03 vs 328.85 and 20.61 cases/100 pt-years, respectively; 2 deaths (1 case each of myocardial infarction and small-cell lung cancer) and 1 case of disseminated tuberculosis were reported.
Conclusion: In a diverse group of pts with RA, treatment with CZP was associated with rapid efficacy and improvements in disease activity and physical function up to 28 weeks, irrespective of concomitant DMARDs, prior TNF inhibitor therapy, or duration of disease.
1. Weinblatt M, et al. Arthritis Rheum 2010;62(suppl 10):S752–S753.
2. Weinblatt M, et al. Ann Rheum Dis 2011;70(suppl 3):414.
Disclosure: M. E. Weinblatt, UCB Inc, 2, UCB Inc, 5 ; R. M. Fleischmann, UCB Inc, 2, UCB Inc, 5 ; R. F. van Vollenhoven, UCB Inc, 2, UCB Inc, 5 ; P. Emery, UCB Inc, 2, UCB Inc, 5 ; T. W. J. Huizinga, UCB Inc, 5 ; M. Cutolo, None; R. Goldermann, UCB Inc, 3 ; B. Duncan, UCB Inc, 3 ; O. Davies, UCB Inc, 1, UCB Inc, 3 ; M. Dougados, UCB Inc, 2, UCB Inc, 5 .