What Drug Should RA Patients Be Switched to After Tocilizumab Failure?

Treatment with a tumor necrosis factor inhibitor (TNFi) may be more effective than abatacept (ABT) in achieving clinical remission in patients with rheumatoid arthritis (RA) who failed to show sufficient response to tocilizumab (TCZ), according to research published in Clinical Rheumatology.

Mitsuhiro Akiyama, MD, of the Division of Rheumatology, Department of Internal Medicine at the Keio University School of Medicine in Tokyo, Japan, and colleagues conducted a retrospective, observational clinical study of 527 patients with RA initially treated with TCZ. Of the 84 patients who switched to another biologic agent due to an insufficient response to TCZ, 63 met study criteria for enrollment, which included persistent moderate or high disease activity, as assessed by the Clinical Disease Activity Index (CDAI).

Patients making the switch were divided into 2 groups: the TNFi group (n=42) received treatment with agents including infliximab, adalimumab, etanercept, golimumab, and certolizumab-pegol; the other group received treatment with ABT (n=21). Both groups were compared for clinical effectiveness and adverse events at week 24.

At week 24, the proportion of patients who achieved low disease activity or remission, as defined by CDAI ≤10, was significantly higher in the TNFi group compared with the ABT group (64.3 vs 23.8 %, P=.003).   

Patients in the TNFi group also had significantly lower 28-joint swollen joint counts (SJC28) at week 24 compared to patients switched to ABT (2.6 ± 0.5 vs 4.9 ± 1.1, P=.013). However, no noted difference in 28-joint tender joint counts (TJC28) were found between the 2 treatment groups.

Rates of drug retention at 24 weeks did not differ between treatment groups (TNFi, 73.8 %; ABT, 71.4 %, P=.803). In addition, neither group reported serious adverse events through 24 weeks. After multivariate logistic regression analysis was performed adjusting for differences in baseline methotrexate use (a characteristic that differed between treatment groups), the researchers found that TNFi use was independently predictive of CDAI ≤10 (odds ratio for TNFi use, 5.76; 95 % confidence interval 1.76 to 18.6, P=.004).

Summary and Clinical Applicability

In this study, RA patients who were switched to a TNFi after demonstrating initial insufficient responses to TCZ achieved a higher degree of disease remission (defined by CDAI≤10) compared to patients who were switched to ABT. In addition, patients assigned to the TNFi group also had significantly lower SJC28 at week 24 compared to those patients switched to ABT.

The study authors concluded: “[W]e suggest that next therapeutic choice in those [patients with RA] not responding to TCZ should take into account the clinical target (remission or LDA) and a history of TNFi failure.”

Limitations and Disclosures

These findings were limited by the small study sample size and the retrospective nature of this study.

Reference

Akiyama M, Kaneko Y, Kondo H, Takeuchi T. Comparison of the clinical effectiveness of tumor necrosis factor inhibitors and abatacept after insufficient response to tocilizumab in patients with rheumatoid arthritis [published online ahead of print March 12, 2016]. Clin Rheumatol. 2016; doi: 10.1007/s10067-016-3227-8.