Certolizumab Pegol Maintenance Research Articles

Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction

BackgroundThe best strategy for maintaining clinical remission in patients with axial spondyloarthritis (axSpA) has not been defined. C-OPTIMISE compared dose continuation, reduction and withdrawal of the tumour necrosis factor inhibitor...

Long-Term Efficacy and Safety of Certolizumab Pegol in an Unselected Crohn's Disease Population: The FACTS III Survey

Background: Long-term data of certolizumab pegol (CZP) in Crohn's disease (CD) from pivotal registry trials are limited. We therefore aimed to evaluate the long-term efficacy of CZP in clinical practice in Switzerland. Methods: In the First Approved Certolizumab Therapeutic Experience in Switzerland-III phase IV multicenter cohort, patients receiving CZP were prospectively included all over Switzerland in (non-) academic hospitals and private practice. Results: We included 104 CD patients (52 male; only 22.1% anti-tumor necrosis factor (TNF) naïve, CZP as third anti-TNF agent in 46.2%) with follow-up time between 6 weeks up to 5 years. During treatment with CZP, we observed a significant decrease of the Harvey Bradshaw Index from a median of 7 at baseline (interquartile range 4-11) to 4, 5, 4, 3, 3, and 2 at weeks 6, 26, 52, 78, 104, and 156, respectively. While anti-TNF naïve patients showed a significantly better response at the end of induction, during CZP maintenance therapy response was similar as compared to anti-TNF experienced patients as well as between patients with a short (0-5 years) vs. long duration of disease (>5 years). Conclusions: CZP is an effective long-term treatment option, including CD patients with long disease duration and prior treatment with 1 or 2 anti-TNF agents.

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

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 Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every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.

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients who could not receive methotrexate: 52-week results from an open-label extension of the HIKARI study

Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients who could not receive methotrexate (MTX).Methods. HIKARI double-blind (DB) patients were entered into an open-label extension (OLE) study. Patients withdrawn at 16 weeks due to lack of efficacy and DB completers without a 24-week American College of Rheumatology (ACR)20 response received CZP 200 mg every 2 weeks (Q2W). DB completers with 24-week ACR20 responses were randomized to CZP 200 mg Q2W or CZP 400 mg every 4 weeks.Results. The ACR20/ACR50/ACR70 response rates of DB completers (n = 98) were 82.7%/56.1%/34.7% at OLE entry, and 83.7%/65.3%/48.0% at 52 weeks, respectively. Other clinical, functional, and radiographic outcomes were sustained during long-term administration of CZP, even without MTX. No new unexpected adverse events were observed during long-term CZP treatment. The efficacy and safety of CZP treatment were similar between the two dosing schedules.Conclusions. Long-term CZP administration is efficacious and safe for RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules. The choice between two maintenace regimens adds flexibility in administration schedules for RA patients and physicians.

Clinically Meaningful Improvement in Health-Related Quality of Life in a Randomized Controlled Trial of Certolizumab Pegol Maintenance Therapy for Crohn's Disease

Moderate-to-severe Crohn's disease (CD) is associated with important impairment in health-related quality of life (HRQOL). The aim of this study was to assess the effects of certolizumab pegol (CZP) maintenance therapy on HRQOL. During an open-label induction phase, study participants with moderate-to-severe CD were treated with 400 mg CZP every other week. Responders were randomized to monthly maintenance therapy with CZP or placebo. Clinically meaningful improvement in HRQOL was evaluated with three patient-reported outcome (PRO) instruments. Quality-adjusted life-years (QALYs) were calculated from utility scores derived from the EuroQoL-5 dimensions (EQ-5D). Normal life rating was measured by combining clinical disease activity, HRQOL, and measures of professional work productivity and daily activity. A total of 425 responders to induction therapy were randomized to CZP maintenance (n=215) or placebo (n=210). Participants assigned to CZP maintenance reported clinically meaningful improvements in HRQOL relative to baseline and to placebo-treated participants. More participants receiving treatment with CZP reported clinically meaningful improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score (60 vs. 43%, P<0.001) and in Short-Form 36-Item Health Survey (SF-36) physical (51 vs. 34%, P<0.001) and mental component summary responses (44 vs. 32%, P=0.016) than did those receiving placebo. The proportion of participants who achieved clinically meaningful improvement in the EQ-5D plus health status visual analogue scale (VAS) was significantly greater in those assigned to CZP maintenance than in those assigned placebo (57 vs. 38%, P<0.001). There was also a significantly greater gain in QALYs for the CZP group as compared with the placebo group (mean+/-s.d. 0.25+/-0.10 and 0.21+/-0.11; P=0.001). Significantly more participants receiving CZP maintenance reported living a normal life (21.4%) than did those receiving placebo (12.9%, P=0.019). Maintenance therapy with CZP resulted in statistically significant and clinically meaningful improvements in HRQOL, as assessed by multiple PRO instruments. CZP improved and maintained the quality and quantity of the remission and response, as measured by QALYs. Furthermore, a significant proportion of study participants who received CZP returned to a normal life compared with those who received placebo.

Efficacy and tolerability of certolizumab pegol are sustained over 18 months: data from PRECiSE 2 and its extension studies (PRECiSE 3 and 4)

PRECiSE 2, a 26-week, open-label induction, double-blind maintenance trial, demonstrated that certolizumab pegol — an Fc-free PEGylated Fab' anti-TNF— is effective and well-tolerated in active Crohn's disease (CD).1 Patients could enter openlabel extension studies evaluating long-term continued maintenance of response (PRECiSE 3) or re-induction and maintenance after relapse (PRECiSE 4). PRECiSE 3 and PRECiSE 4 are ongoing studies; results after 12 and 18 months' treatment are presented here. In PRECiSE 2, responders to open-label induction (Weeks 0, 2, 4) with certolizumab pegol 400 mg (64.1%) were randomized at Week 6 to certolizumab pegol 400 mg (n =215) or placebo (n=210) every 4 weeks (Week 8-24). Patients completing PRECiSE 2 could enter PRECiSE 3 and continued to receive certolizumab pegol 400 mg every 4 weeks for up to 5 years. Patients who relapsed (Crohn's Disease Activity Index [CDAI] score increase ≥70 points or CDAI score ≥350 points) after randomization in PRECiSE 2 were eligible to enter PRECiSE 4 and receive re-induction with certolizumab pegol 400 mg (Weeks 0, 2, 4) followed by maintenance dosing every 4 weeks (i.e., re-induction from PRECiSE 2 into PRECiSE 4 was a single additional dose). In PRECiSE 3 and PRECiSE 4, efficacy was assessed by the Harvey-Bradshaw Index (HBI: remission = HBI score ≤4; response = HBI decrease ≥3).2 Patients lost to follow-up or withdrawn were treated as non-responders. By Week 26 of PRECiSE 2, remission was achieved by 47.9% (103/215) of patients receiving certolizumab pegol (n =215). In an ITT-like analysis of the active arm in which all patients lost to follow up were classified as “failures”, 40.9% (88/215) achieved remission after 12 months of continued treatment in PRECiSE 3. After 18 months, 36.3% (78/215) remained in remission. Among patients that became active and were re-induced with certolizumab pegol in PRECiSE 4, 28.6% (14/49) achieved remission. The remission rate after re-induction was stable (34.7%17/49 6 and 12 months after starting PRECiSE 4). Among patients from the PRECiSE 2 placebo group who were re-induced with certolizumab pegol in PRECiSE 4, 44.0% (33/75) achieved remission. Remission rates were 44.0% (33/75) after 6 months and 36.0% (27/75) after 12 months. No new safety signals were identified following re-exposure of placebo patients from PRECiSE 2 to certolizumab pegol. Certolizumab pegol-induced remission in patients with CD is characterized by a remarkable long-term durability. Re-induction with a single supplemental dose of certolizumab pegol 400 mg after loss of response under certolizumab pegol maintenance was a well-tolerated, successful therapeutic strategy.