The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo - PubMed (original) (raw)
Clinical Trial
. 2009 Jul;60(7):1895-905.
doi: 10.1002/art.24567.
Affiliations
- PMID: 19565475
- DOI: 10.1002/art.24567
Free article
Clinical Trial
The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo
Joel M Kremer et al. Arthritis Rheum. 2009 Jul.
Free article
Erratum in
- Arthritis Rheum. 2012 May;64(5):1487
Abstract
Objective: To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response.
Methods: Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks.
Results: By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all CP-690,550 treatment arms.
Conclusion: Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.
Trial registration: ClinicalTrials.gov NCT00147498.
Comment in
- JAK inhibition in rheumatoid arthritis.
Patel AM, Lupash D, Chew D, Levesque MC, Moreland LW. Patel AM, et al. Curr Rheumatol Rep. 2011 Oct;13(5):379-80. doi: 10.1007/s11926-011-0196-4. Curr Rheumatol Rep. 2011. PMID: 21728017 No abstract available.
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