Background/Purpose:

For active rheumatoid arthritis patients with inadequate response to synthetic disease modifying antirheumatic drugs (DMARDs), biologic agents are indicated. However, the cost of biologics, including tocilizumab (TCZ), is very high, which makes it difficult for all patients to receive biologics because of the associated expenses. A period of 4 weeks has been recommended as the interval between TCZ infusions in active rheumatoid arthritis patients (1). In our clinical experience, however, we observed that longer intervals could also be effective. The aim of the present study was to clarify that not only 5 but also 6 weeks intervals of TCZ infusion induce clinical remission in patients with active rheumatoid arthritis.

Methods:

 The rheumatoid arthritis patients who showed inadequate response to synthetic DMARDs and the patients who showed inadequate response to TNF inhibitors and who agreed with TCZ therapy of six weeks interval were enrolled in the present study. Initially, active rheumatoid arthritis patients were infused with 8 mg/kg of TCZ every 6 weeks with oral medicines. The patients who did not achieve clinical remission after 6 months of TCZ infusions at 6 weeks intervals were administered TCZ infusions every 5 weeks or 4 weeks, along with the same doses of the oral medicines. After one year of treatment with same intervals, we evaluated the clinical conditions. The disease activities were evaluated with clinical symptoms, VAS, CRP, and DAS28 score, and clinical remission was estimated as DAS28 score less than 2.6.

Results: In total, 103 patients were enrolled in the present study, and 82% of patients achieved clinical remission with TCZ infusion. Twelve patients did not achieve clinical remission even at 4 weeks intervals. Seven patients dropped out from the study because of personal reasons. Among the patients who achieved clinical remission with TCZ infusion, 71% of patients were with 6 weeks intervals, and 24% were with 5 weeks intervals. To our surprise, the patients who needed 4 weeks intervals of TCZ infusions to achieve remission were less than 5%. In patients who achieved remission with 6 weeks intervals of TCZ infusion, 27% could discontinue both prednisolone (PSL) and methotrexate (MTX), 43% received PSL (5 to 1mg), and 3% received MTX, and 27% received PSL and MTX. Severe adverse events that led to the discontinuation of treatment, including tuberculosis and death, did not occur, and the frequency of other adverse events with infusions at 6 weeks intervals was lower than that at 4 weeks intervals.

Conclusion:

 The present study has provided evidence that not only 5 but also 6 weeks intervals of TCZ infusion induce clinical remission in patients with active rheumatoid arthritis, and the finding should be of great interest for patients for both financial and labor reasons.

Reference:

(1) Roshe Registration Limited. RoACTEMRA 20 mg/ml concentrate for solution for infusion. Welwyn Garden City, UK: Roshe Registration Limited, 2012

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/not-only-5-but-also-6-weeks-intervals-of-tocilizumab-infusion-induce-clinical-remission-in-patients-with-active-rheumatoid-arthritis/