Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

Abstract

Objectives: To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate.

Methods: J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate.

Results: The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules.

Conclusions: Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules.

Keywords: Certolizumab pegol; Clinical study; Rheumatoid arthritis; TNF inhibitor; TNFα.

Figure 1.

J-RAPID OLE study design. The diagram depicts the breakdown of J-RAPID DB study patients into four groups for the OLE phase of the study. *Regardless of their initial DB phase group assignment, patients who achieved an ACR20 response at weeks 12 or 14 as well as at week 24 were randomized (1:1) to either CZP 200 mg Q2W (Group III, n = 93) or CZP 400 mg Q4W (Group IV, n = 92).

Figure 2.

The ACR20/ACR50/ACR70 response rates in patients from each treatment group. The percentages of patients in Groups I (n = 81), II (n = 19), III (n = 93), IV (n = 92) and patients in Groups II + III+ IV combined (DB completers, n = 204) who achieved an (a) ACR20, (b) ACR50, or (c) ACR70 response were plotted over time for the DB and the OLE phase of the study (FAS population, LOCF imputation). Of note, week 0 of the OLE phase of Group I (early escape) corresponds to week 16 of the DB phase. There are no points in the missing section of the graph for Group I.

Figure 3.

The changes of DAS28-ESR and HAQ-DI over J-RAPID pre-study baseline in patients from each treatment group. Changes in (a) DAS28-ESR and (b) HAQ-DI from J-RAPID pre-study baseline of Groups I (n = 81), II (n = 19), III (n = 93), IV (n = 92) and patients in Groups II + III+ IV combined (DB completers, n = 204) were plotted against time for the DB and the OLE phase of the study (FAS population, LOCF imputation). Of note, week 0 of the OLE phase of Group I (early escape) corresponds to week 16 of the DB phase. There are no points in the missing section of the graph for Group I.

Figure 4.

Inhibition of progression of structural damage: cumulative probability plot representing the change from OLE study entry in mTSS at week 52 (FAS population, linear extrapolation). The graph depicts the cumulative probability of patients displaying a particular change in mTSS from OLE study entry in Groups I (n = 67), II (n = 16), III (n = 87), IV (n = 83) and patients in Groups II + III+ IV combined (DB completers, n = 186).

Figure 5.

Post-hoc analysis of ACR20/ACR50/ACR70 response rates in patients from Groups II, III and IV excluding those who were in the placebo group during the DB phase (CZP-DB completers). The ACR20, ACR50 and ACR70 response rates of post-hoc analysis patients treated with (a) 100 mg (n = 51), (b) 200 mg (n = 63) or (c) 400 mg (n = 65) of CZP during the DB phase were plotted against time for the DB and the OLE phase of the study (LOCF imputation).

Figure 6.

Post-hoc analysis of changes in (a) DAS28-ESR and (b) HAQ-DI scores from J-RAPID pre-study baseline in patients from Groups II, III and IV excluding those who were in the placebo group during the DB phase (CZP-DB completers). The changes of DAS28-ESR and HAQ-DI scores of post-hoc analysis patients treated with 100 mg (n = 51), 200 mg (n = 63) or 400 mg (n = 65) of CZP during the DB phase were plotted against time for the DB and the OLE phase of the study (LOCF imputation).

Figure 7.

Post-hoc analysis of disease activity states in patients from Groups II, III and IV excluding those who were in the placebo group during the DB phase (CZP-DB completers). The proportions of patients with high (defined as DAS28-ESR > 5.1), moderate (> 3.2 and ≤ 5.1), low (≤ 3.2), or remission (< 2.6) disease activity states at DB week 0 (DB0), DB week 24 (DB24), OLE week 0 (OLE0), OLE week 24 (OLE24) and OLE week 52 (OLE52) among patients treated with (a) 100 mg (n = 51), (b) 200 mg (n = 63) and (c) 400 mg (n = 65) during the DB phase are shown (LOCF imputation).