RESEARCH - The safety and efficacy of a JAK inhibitor in patients with active RA

[Guest guest]

Arthritis Rheum. 2009 Jun 29;60(7):1895-1905.

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.

Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D,

Krishnaswami S, Burgos-Vargas R, Wilkinson B, Zerbini CA, Zwillich SH.

Albany Medical College, Albany, New York.

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.

PMID: 19565475

http://www.ncbi.nlm.nih.gov/pubmed/19565475

Not an MD