Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

OBJECTIVE: To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN). METHODS: A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26. RESULTS: A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7-95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9-75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5-10%) and severe infections (10% vs. 4.8-5.0%) were reported with 240 mg BI 655064. CONCLUSION: The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.

Tocilizumab treatment of rheumatoid arthritis among Filipino patients

Introduction. Studies have shown that tocilizumab (TCZ) is effective in the treatment of rheumatoid arthritis. This study examined the efficacy and safety of TCZ in Filipino patients with moderate to severe rheumatoid arthritis (RA). Methods. This was an open-label, one-arm clinical trial approved by the Philippine Council Health Research Development-National Ethics Committee (PCHRD-NEC), among moderate-severe active RA Filipino patients in 4 RA clinics. The study consisted of a 28-day screening-baseline period; a 24-week treatment period, with once every-4-weeks TCZ 8mg/kg intravenous infusion (IV) and an efficacy-safety evaluation. Patients already receiving methotrexate (MTX) at study entry went on with MTX plus TCZ per medical discretion. Descriptive statistics computed for physician's and patient's global assessment of disease activity, patient's global assessment of pain, ACR20, ACR50 and ACR70. Analysis of variance (ANOVA) determined significant changes over time for DAS-28 ESR, FACIT and HAQ-DI fatigue scores. Twenty-nine of thirty patients were included in efficacy and safety analysis. Results. After 24 weeks of TCZ: 86%, 66%, and 48% of 29 Filipino RA patients achieved ACR20, ACR50, ACR70, respectively, with 34% achieving remission according to DAS28-ESR. Median times to first achieving ACR20, ACR50 and ACR70 were 4, 12, and 24 weeks, respectively. There were also significant rapid reductions in physician's and patient's global assessment of disease activity, patient's global assessment of pain, HAQ-DI and FACIT scores noted over time. Tolerability profile was similar to published literature on TCZ. Conclusions. TCZ has been shown to be effective in the treatment of Filipino patients with moderate to severe rheumatoid arthritis. TCZ can be given in an out-patient RA clinic setting.