• Rheumatology Clinical Trials
• Rheumatoid Arthritis

When used in combination with traditional disease-modifying antirheumatic drugs (DMARDs), response rates were significantly superior with a subcutaneous (SC) form of tocilizumab compared with placebo in a 24-week Phase 3 study of patients with moderate to severe rheumatoid arthritis (RA).

A SC form of tocilizumab gives patients the opportunity to self-administer treatment, reported Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA. 656 patients with moderately to severely active RA of at least 6 months duration and an inadequate response to 1 or more DMARDs (20% had prior treatment with anti-TNF) were randomized in a 2:1 ratio to treatment with SC tocilizumab (n=437; 162 mg every 2 weeks) or SC placebo (n=219) with continuation of DMARDs [Kivitz AJ et al. ACR 2012 Poster L8]. Oral corticosteroids and nonsteroidal anti-inflammatory drugs were permitted if patients were on stable dosages for at least 4 weeks prior to baseline.

Significantly more patients treated with SC tocilizumab compared with placebo achieved an American College of Rheumatology 20% improvement response (ACR20) at Week 24, the primary endpoint of the study (61% vs 31.5%, respectively; p<0.0001).

Achievement of secondary endpoints also favored SC tocilizumab.

• An ACR50 response was achieved by 40% assigned to SC tocilizumab compared with 12% assigned to placebo (p<0.0001), and an ACR70 response occurred in 20% versus 5%, respectively (p<0.0001)

• The adjusted mean change in the 28-joint Disease Activity Score was −3.1 in the tocilizumab group and −1.7 in the placebo group (p<0.0001)

• The adjusted mean change in the Health Assessment Questionnaire Disability Index from baseline to Week 24 was −0.40 in the tocilizumab group versus −0.30 in the placebo group (p=0.0054)

• The change in the modified Total Sharp Score from baseline to Week 24 was 0.62 in the tocilizumab group versus 1.23 in the placebo group (p=0.0149), reflecting less progression of joint damage in the tocilizumab group

Neutropenia occurred more often in patients receiving SC tocilizumab compared with placebo (20.5% vs 3.7%); however, the proportion of patients experiencing infections or serious infections was similar in both groups. There were no cases of thrombocytopenia in patients assigned to placebo; Grade 1 thrombocytopenia occurred in 6.7% and Grade 2 thrombocytopenia occurred in 0.5% of the patients assigned to SC tocilizumab, with no instances of either Grade 3 or 4 thrombocytopenia. Elevated transaminases were more common in patients who received SC tocilizumab; few alanine and aspartate aminotransferase elevations were >3 times the upper limit of normal in SC tocilizumab-treated patients (3.7% and 0.7%, respectively).

The authors concluded that the superior efficacy responses and similar safety profile of SC tocilizumab compared with placebo offers patients an alternate route of administration for tozilizumab therapy in RA.

• © 2012 MD Conference Express®