Efficacy and safety of abatacept in biologic-naïve patients with active rheumatoid arthritis by background methotrexate dose: post hoc analysis of a randomized, placebo-controlled, phase 4 study.

OBJECTIVES: The objective of this study is to evaluate efficacy and safety of abatacept in biologic-naïve, anti-citrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) by background methotrexate (MTX) dose. METHODS: In this post hoc analysis of a randomized, double-blind, placebo-controlled phase 4 study (NCT01758198), patients received intravenous abatacept (∼10 mg/kg) or placebo both with MTX (≥6 mg/week). Efficacy (Disease Activity Score 28 using C-reactive protein [DAS28 (CRP)] and Health Assessment Questionnaire-Disability Index [HAQ-DI]) was assessed by baseline MTX dosage (≤8 and >8 mg/week) to week 16; safety was assessed by MTX dosage ≤8 and >8 mg/week. Change from baseline in DAS28 (CRP) and HAQ-DI was assessed using longitudinal repeated measures analysis. RESULTS: Overall, 101 and 102 patients received abatacept + MTX ≤8 and >8 mg/week, while 96 and 106 patients received placebo + MTX ≤8 and >8 mg/week, respectively. Regardless of baseline MTX dose received, mean changes from baseline in DAS28 (CRP) and HAQ-DI in abatacept groups were similar; repeated measures analysis showed similar trends in changes from baseline in DAS28 (CRP) and HAQ-DI. Abatacept safety profile was consistent with previous observations. CONCLUSIONS: Post hoc analysis demonstrated similar efficacy and safety of abatacept in biologic-naïve ACPA-positive Japanese patients with RA regardless of baseline MTX dose.

Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study.

BACKGROUND: To investigate efficacy and safety of intravenous abatacept in Japanese patients with active polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: In this phase III, open-label, multicenter, single-arm study, patients with pJIA aged 4-17 years who failed ≥1 biologic or methotrexate received weight-tiered (< 75 kg: 10 mg/kg; 75-100 kg: 750 mg; > 100 kg: 1000 mg) intravenous abatacept at Weeks 0, 2, 4, and every 4 weeks thereafter. The study comprised a short-term period (16 weeks) and ongoing long-term period. Primary endpoint: Week 16 JIA-American College of Rheumatology criteria 30 (JIA-ACR30) response rate. Secondary endpoints/outcomes included Week 16 JIA-ACR50/70/90 response and inactive disease rates, Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), pharmacokinetics, safety, and immunogenicity. Proportions of patients achieving Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP) remission (score < 1) and minimal disease activity (MDA; score < 3.8), were among exploratory endpoints. RESULTS: All 20 patients who received study medication completed the short-term period. During the long-term period, two patients discontinued due to insufficient efficacy or patient decision. Median age and disease duration at baseline were 10.5 and 0.75 years, respectively. Week 16 JIA-ACR30 response rate (primary endpoint) was 90.0% (18/20). JIA-ACR50/70/90 response and inactive disease rates at Week 16 were 75.0% (15/20), 70.0% (14/20), 35.0% (7/20), and 25.0% (5/20), respectively. At Week 52, JIA-ACR30/50/70/90 response and inactive disease rates were observed by 88.9% (16/18), 88.9% (16/18), 83.3% (15/18), 66.7% (12/18) and 44.4% (8/18), respectively. CHAQ-DI improved after Week 12. JADAS27-CRP remission and MDA were achieved by 15.0% (3/20) and 45.0% (9/20) of patients at Week 16, and by 50.0% (9/18) and 78.0% (14/18) of patients at Week 52, respectively. The mean abatacept pre-dose serum concentration was above the target therapeutic exposure (10 µg/ml) from Week 8 through Week 16. All adverse events were of mild/moderate intensity, except for one case of severe gastroenteritis. No deaths, malignancies, or autoimmune disorders were observed. No antidrug antibodies were detected through Week 16; one patient had a positive immunogenic response during the cumulative period. CONCLUSION: Intravenous abatacept was efficacious and well tolerated in Japanese patients with active pJIA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01835470 . Date of registration: April 19, 2013.

Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis: a randomised placebo-controlled phase IV study.

OBJECTIVES: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. METHODS: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. RESULTS: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic non-progression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. CONCLUSIONS: Compared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.

A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy.

PURPOSE: To evaluate the efficacy and safety of weekly paclitaxel (Taxol(®)) in patients with advanced or recurrent esophageal cancer. METHODS: Fifty-three patients with recurrent or advanced esophageal cancer who had previously received platinum-based chemotherapy were treated with paclitaxel 100 mg/m(2) once weekly by 1-h infusion on days 1, 8, 15, 22, 29, and 36 of a 49-day cycle. Fifty-two patients were evaluable for efficacy and 53 for safety. Forty-one (77%) patients had recurrent, and 12 (23%) had advanced disease. Most patients (52/53) had squamous cell carcinoma, and one had adenocarcinoma. RESULTS: A median of 2 cycles was delivered (range 1-8). The overall response rate was 44.2% (23/52; 95% confidence interval (CI) 30.5, 58.7%), with 4 patients (7.7%) achieving complete response. The median duration of response was 4.8 months, and median overall survival was 10.4 months. The most common Grade 3 or 4 adverse events were neutropenia (52.8%), leukopenia (45.3%), anorexia (9.4%), and fatigue (9.4%). Adverse events resulted in treatment discontinuation in 34.0% of patients and dose reductions in 43.4%. There were no treatment-related deaths. CONCLUSIONS: Weekly paclitaxel demonstrated efficacy and manageable toxicity in patients with advanced or recurrent esophageal cancer and may be a treatment option for this population.