Background The effectiveness and safety of subcutaneous tocilizumab 162 mg every other weeks (TCZ-SC) monotherapy were shown to be comparable to those of intravenous tocilizumab 8 mg/kg every 4 weeks (TCZ-IV) monotherapy in Japanese patients with rheumatoid arthritis (RA) in a double-blind, parallel-group, phase III non-inferiority study (MUSASHI study)1). In the presence of serum trough TCZ level of ≥1 µg/mL, adequate suppression of IL-6 signalling during TCZ-IV treatment results in normalization of serum CRP levels.2)
Objectives To investigate whether patients with normalization of serum CRP level by 12 weeks during administration of TCZ-SC achieved a clinical response at Week 24.
Methods This was a post hoc analysis from the MUSASHI study. Patients with RA who had responded inadequately to any synthetic or biologic DMARD were randomized to receive 162 mg TCZ-SC every 2 weeks (TCZ-SC group) or 8 mg/kg TCZ-IV every 4 weeks without any concomitant DMARDs. Week 24 efficacy endpoints including rates of ACR response and DAS28/CDAI remission were assessed and stratified by normalization of serum CRP level (≤0.3 mg/dL) at Week 4, 8, and 12 in the TCZ-SC group.
Results The efficacy analyses included 159 patients who were eligible for the per protocol analysis in the TCZ-SC group. At Week 24, 79.2% of patients in the TCZ-SC group achieved ACR20, 63.5% achieved ACR50, 37.1% achieved ACR70, 49.7% achieved DAS28 remission, and 16.4% achieved CDAI remission. Serum CRP level was normalized (≤0.3 mg/dL) in most patients (90.6%, 144/159)at Week 24. Serum CRP level was normalized in 99.2% (1679/1693 points) in the presence of serum trough TCZ level of ≥1 µg/mL. ACR20 response rate at Week 24 was 84.7% (122/144) in the patients with normalized CRP vs. 26.7% (4/15) in the patients without normalized CRP at Week 24. The groups with normalized CRP at Weeks 4, 8, or 12 had higher ACR response rates and DAS28/CDAI remission rates at Week 24 than the groups without normalized CRP (Table). No patients without normalized CRP at Week 8 or later achieved DAS28/CDAI remission at Week 24.
Conclusions Serum CRP level was normalized in most points with serum trough TCZ level of ≥1 µg/mLduring TCZ-SC treatment. In this TCZ-SC monotherapy setting, patients who had normalized CRP by Week 12 achieved higher rates of DAS28/CDAI remission and ACR response at Week 24 than the patients without normalized CRP. The efficacy at Week 24 was predictable by CRP normalization at Week 4. Patients whose CRP has not normalized despite 8 weeks of TCZ-SC treatment will possibly not achieve an adequate response.
Ogata A. Ann Rheum Dis 2012;71(Suppl3):373
Nishimoto N et al. Blood. 2008;112(10):3959-64.
Disclosure of Interest: A. Ogata Consultant for: Chugai pharmceuticals