Arthritis and Arthritic Pain (Pediatric)

April 11, 2016

Eli Lilly reported results of a phase III trial of baricitinib for moderate-to-severe rheumatoid arthritis (RA). The RA-BEACON study enrolled 527 patients who previously had failed at least one tumor necrosis factor (TNF) inhibitor, and included 199 patients who also had received prior treatment with one or more non-anti-TNF biologic agents. Patients received baricitinib 2mg or 4mg or placebo daily, in addition to their existing background therapies, for 24 weeks. The study met its primary endpoint of improved ACR 20 response for baricitinib compared with placebo at week 12. ACR 20 represents at least a 20% improvement across selected measures of disease activity. ACR 20 response rates were as follows (P≤0.001 for each baricitinib dose versus placebo): 55% for baricitinib 4mg, 49% for baricitinib 2mg and 27% for placebo. A statistically significant improvement in ACR 20 response rate with baricitinib versus placebo was observed as early as one week (P≤0.01). ACR 50 and ACR 70 response rates were also significantly higher for baricitinib compared with placebo at week 12 (P≤0.01). A significantly greater proportion of patients treated with baricitinib also achieved a DAS28-CRP scorea measure of RA disease activitybelow 2.6 (indicating disease remission) at week 12 compared with patients receiving placebo. Additionally, a greater proportion of patients treated with baricitinib versus placebo achieved score improvements of at least 0.3 on the Health Assessment Questionnaire Disability Index (HAQ-DI), a patient-reported assessment of physical function at week 12. Significant improvements in ACR response rates, DAS28-CRP and HAQ-DI that were noted with baricitinib versus placebo at week 12 were maintained through week 24. Through 24 weeks, the rate of treatment-emergent adverse events (AEs) was higher for baricitinib 4mg (77%) and baricitinib 2mg (71%) than for placebo (64%).

January 7, 2013

Novartis published results of a phase III trial of ACZ885 (canakinumab) for the treatment of systemic juvenile idiopathic arthritis (SJIA). This four-week, randomized, double-blind, placebo-controlled study, Beta-SPECIFIC 1, enrolled 84 patients between ages two and 19 with active SJIA. Subjects received a single subcutaneous dose of 4mg/kg (up to 300mg) ACZ885 or placebo. Data demonstrated 84% of patients treated with ACZ885 experienced at least a 30% improvement in symptoms compared to 10% for placebo after 15 days of treatment, which was sustained after 29 days (p<0.001). Additionally, ACZ885-treated patients were nearly three times less likely to experience a new flare, with 74% of ACZ885-treated patients remaining flare-free, compared to 25% with placebo (p=0.003). The drug was well tolerated. Based on these data, Novartis pursued regulatory submission in the U.S. and Europe.

April 23, 2012

UCB Pharma reported results from a phase III trial of certolizumab pegol for axial spondyloarthritis (AxSpA). This 24-week, multicenter, double-blind, placebo-controlled trial enrolled 325 subjects with AxSpA who were randomized to receive certolizumab pegol at 200 mg every two weeks, 400 mg every four weeks, or placebo. The primary endpoint was at least 20% change in the Assessment of SpondyloArthritis international Society improvement criteria (ASAS20). At week 12 a statistically significant higher proportion of subjects in the certolizumab pegol arm reached this endpoint compared to those in the placebo arm. Sub-population analyses indicated that certolizumab pegol also improved the signs and symptoms of AS and non-radiographic AxSpA. The most frequent adverse events were upper respiratory tract infection, elevated liver function tests and abnormal CPK levels.

September 26, 2011

Novartis released results from a phase III trial of canakinumab for systemic juvenile idiopathic arthritis. This randomized, double-blind, placebo-controlled study enrolled 84 subjects between the ages of 2 and 19 years who received either a single subcutaneous dose of canakinumab (4 mg/kg, up to 300 mg) or placebo for four weeks. The primary endpoint was the proportion of subjects achieving the adapted ACR Pediatric 30 criteria, demonstrating a 30% improvement in at least three of the six variables, from baseline at Day 15. In the canakinumab treatment arm 83.7% of subjects experienced at least a 30% improvement in symptoms versus 9.8% for placebo (p<0.0001), and 32.6% achieved a 100% improvement versus 0% for placebo (p≡0.0001).

November 3, 2008

Novartis reported positive results from two clinical trials of canakinumab for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) and Systemic Juvenile Idiopathic Arthritis (SJIA). The CAPS study was a six month trial in subjects aged nine to 74 years old and was divided into three parts. In the first part, lasting two months, 35 subjects received a single dose of canakinumab by subcutaneous injection. All but one subject showed a rapid and long-lasting clinical and biochemical response. Part two was a randomized six-month, double-blind, placebo-controlled withdrawal design study in 31 subjects who maintained their response. The subjects were treated with canakinumab or placebo every two months. This portion of the study included the primary endpoint, a comparison between the number of subjects treated with canakinumab who experienced disease outbreaks versus those on placebo. Results showed that no subjects in the canakinumab group experienced a disease flare compared to 81% in the placebo group (p<0.001). Markers of inflammation (C-reactive protein and serum amyloid A) were normalized in patients treated with canakinumab, but increased significantly for those on placebo. Part three of the study is underway in subjects who had relapsed. The SJIA study was an open label, repeat dose trial in 26 pediatric subjects with active SJIA. Results showed substantial clinical improvement (measured by the pediatric ACR50 scale) was reached within 15 days. In addition, four subjects achieved complete remission of the disease. Based on the results Novartis plans to continue with the development of canakinumab