Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

Abstract

Tocilizumab, a humanized monoclonal antibody to the interleukin 6 (IL-6) receptor, was approved for use as rheumatoid arthritis (RA) therapy in Japan in 2008, but its efficacy and tolerability in daily practice has not yet been reported. We report the results of a multicenter retrospective study on the efficacy and safety of tocilizumab involving all patients (n = 229) who were started on tocilizumab therapy at three rheumatology institutes in Japan from April 2008 through to March 2009. Tocilizumab was infused every 4 weeks at a dose of 8 mg/kg according to the drug labeling. Among the 229 patients, 55% concomitantly received methotrexate (MTX) and 63% had previously received anti-tumor necrosis factor (TNF) therapy. Average disease activity score (DAS) 28 of all 229 patients significantly decreased from 5.70 to 3.25 after 24 weeks of therapy. A European League Against Rheumatism (EULAR) good response and DAS28 remission was achieved in 57.4 and 40.7% of the patients, respectively, at 24 weeks. White blood cell counts significantly decreased and liver enzymes and total cholesterol slightly but significantly increased; however, liver enzyme levels did not increase in patients without MTX. Tocilizumab was discontinued in 47 cases (20.5%) due to lack of efficacy (5.2%), adverse events (11.4%), and other reasons (3.9%). The overall retention rate at 24 weeks was 79.5%. Based on these results, we conclude that tocilizumab therapy in daily rheumatology practice appears to be highly efficacious and well tolerated among active RA patients, including the anti-TNF therapy-refractory population. Tocilizumab infusion is therefore applicable not only as an alternative approach for anti-TNF therapy-resistant patients, but also as primary biologic therapy for active RA patients.

Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: retrospective analyses of data collected during the first year of adalimumab treatment in routine clinical practice (HARMONY study)

“…The overall retention rate observed in the present study (82.4% at 26 weeks and 69.7% at 52 weeks) falls within the range reported for infliximab (75.6% at 54 weeks) [15], etanercept (85.1% at 6 months) [17], and tocilizumab (79.5% at 24 weeks) [28] in daily clinical practice. However, it is not surprising that the retention rate varies among different biologics, as it is believed to be influenced by numerous factors other than efficacy and safety, such as co-morbidity, concomitant therapy, costs, launch timing, and availability of other therapies [29].…”

Evaluation of safety, efficacy and post-cessation efficacy durability of tocilizumab in patients with active rheumatoid arthritis

“…Frequencies of 22.8–49.2% for clinical remission (DAS28 < 2.6) at week 24, determined in almost all of the mentioned studies, also appear to be less than the 71.4% observed in the present study (with 76.2% as the final cumulative frequency).…”

“…Most of the reference studies reported −2.5 to −3.3 difference between the baseline and the last (week 24) mean DAS28, not far from −3.3 obtained in our study, but with a slower decrement rate . Relatively the same is true for the mean HAQ score, with a similar rate of decrement observed with a lower baseline value (1.1) compared to the references (1.5–1.6).…”

Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules

“…Several studies have shown that a frequent reason for the discontinuation of biological agents is the development of AE 5–7 13–16. Mid to long-term tolerability of TNF inhibitors6 13 14 16–24 and tocilizumab7 15 25 has been reported, and some studies have directly compared drug retention rates among TNF inhibitors or between TNF inhibitors and other biological agents 14 16 17 25–27. To summarise, infliximab had the lowest overall retention rate among infliximab, etanercept and adalimumab14 16 17 and among infliximab, etanercept and anakinra 26.…”