August 11, 2016 • By
A recent study published online in March in the Annals of the Rheumatic Diseases investigated if the infliximab biosimilar (CT-P13, infliximab-dyyb), which is marketed in Europe as Inflectra and Remsima, can be safely and effectively substituted for infliximab (Remicade).1 Infliximab and its biosimilar are manufactured via the same process. Researchers set out to determine whether those patients with antibodies to infliximab would mount a similar response to the infliximab biosimilar (CT-P13). Two-hundred and fifty patients with rheumatoid arthritis (RA) andspondyloarthritis undergoing infliximab treatment who had never been exposed to CT-P13 were evaluated.
All patients treated with infliximab who had antibodies to infliximab cross reacted with CT-P13, either Inflectra or Remsima. The authors note that the epitopes raising the immune response to infliximab demonstrate the same degree of reactivity to the infliximab biosimilar. However, due to different glycosylation patterns or impurities, CT-P13 may possess its own unique epitopes.
The authors caution that patients on infliximab who have developed antibodies to infliximab should not be switched to an infliximab biosimilar because the antibodies to the innovator product may interact with the new infliximab molecule and potentially lead to loss of clinical response and infusion-related reactions.
Early vs. Late bDMARD Initiation
The efficacy of the first bDMARD (biological disease-modifying anti-rheumatic drug) was evaluated in patients with RA following international recommendations on a treat-to-target strategy (n=113) and compared with the delayed initiation of bDMARDs (usual care, n=250) in an outpatient clinic.2 DAS-28 was used to measure disease activity until the end of treatment with the bDMARD. Remission or low disease activity was considered a good response. Treatment efficacy was measured at Months 3, 12, 24 and 36, and at the end of treatment. Kaplan–Meier plots were completed to assess the likelihood of realizing a good response. These plots showed that the likelihood for a good response was significantly higher in the treat-to-target patients (P<0.001).
Efficacy of the three classic bDMARDs—adalimumab, etanercept and infliximab—was comparable. The hazard ratio of the likelihood of achieving a good response was 1.71 (95% CI 1.18–2.47, P=0.004) in favor of the treat-to-target group. A total steroid dose greater than 500 mg and range of six to 10 swollen joints were considered negative predictive factors for a good response. Etanercept and the newer bDMARDs appeared more effective than adalimumab or infliximab.
The authors concluded that a treat-to-target strategy using bDMARDs provides a faster response and better long-term outcomes in RA patients compared with delaying treatment initiation with bDMARDs.
Certolizumab Pegol Combination Therapy
DMARD-naive patients with early rheumatoid arthritis (RA) who used certolizumab pegol along with dose-optimized methotrexate (MTX) experienced sustained remission, sustained low disease activity, improved physical function and inhibited structural damage compared with patients who received dose-optimized MTX along with placebo in a 52-week study.3 Patients enrolled in the study had to have active RA, which was defined as having four or more swollen and four or more tender joints, a Disease Activity Score in 28 joints (DAS28) greater than 3.2, and an erythrocyte sedimentation rate (ESR) of at least 28 mm/h or a C-reactive protein of ≥10 mg/L. The mean patient age was 50, and the majority (approximately 75%) were female.
Researchers randomized 879 patients in a 3:1 ratio via a double-blind method to receive 400 mg certolizumab pegol at Weeks 0, 2 and 4 and then 200 mg certolizumab pegol every two weeks through Week 52 along with MTX (n=660), or placebo and MTX (n=219; either 15 mg or 25 mg weekly). The primary efficacy endpoint was the proportion of patients in sustained remission (DAS [ESR] <2.6) at both Weeks 40 and 52. The secondary endpoint was the proportion of patients with sustained low disease activity (DAS28 [ESR] ≤3.2) at both Weeks 40 and 52.
Study authors caution: Patients on infliximab who have developed antibodies to infliximab should not be switched to an infliximab biosimilar.
At Week 52, 29% vs. 15% (P<0.001) of certolizumab pegol plus MTX and MTX-only treated patients, respectively, achieved sustained remission. Additionally, 44% vs. 29% (P<0.001) of certolizumab pegol plus MTX and MTX-only treated patients, respectively, achieved sustained low disease activity. For certolizumab pegol plus MTX-treated patients, there was significantly greater inhibition of radiographic progression and physical functioning improvement vs. MTX plus placebo-treated patients. Of all randomized patients, 143 of placebo plus MTX-treated patients completed Week 52 and 500 certolizumab pegol plus MTX-treated patients completed Week 52.
Adverse events and serious adverse events were similar between both treatment groups. Infection occurred more frequently in the certolizumab pegol plus MTX-treated patients. Serious infection rates were similar between the two treatment groups. Two deaths occurred in the certolizumab pegol-treated group: one from a stroke not believed to be medication related, and one from a disseminated, mycobacterium infection thought to be medication related. One death also occurred in the MTX plus placebo-treated group that was not thought to be treatment related.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- Ruiz-Argüello B, Maguregu A, Ruiz del Agua A, et al. Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity towards biosimilar CT-P13. Ann Rheum Dis. 2016 Mar 10. pii: annrheumdis-2015-208684. doi: 10.1136/annrheumdis-2015-208684. [Epub ahead of print]
- Lampropoulos CE, Orfanos P, Manoussakis M, et al. Efficacy of treat-to-target biologic therapy in patients with rheumatoid arthritis compared to delayed initiation of biologics: A real world study. Ann Rheum Dis. 2016;75(Suppl2):193. doi: 10.1136/annrheumdis-2016-eular.1187
- Emery P, Bingham III CO, Burmester GR, et al. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naive patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled Phase III study. Ann Rheum Dis. 2016 May 10. pii: annrheumdis-2015-209057. doi: 10.1136/annrheumdis-2015-209057. [Epub ahead of print].