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CRP Predicts Drug Efficacy in Psoriatic Arthritis : Another factor that contributed to infliximab's efficacy was absence of hip or knee involvement.


 

The absence of large joint involvement, higher serum C-reactive protein levels, and lower disability scores at treatment initiation may be predictors of a good therapeutic response to infliximab in refractory psoriatic polyarthritis, an open-label study has shown.

The efficacy of infliximab in psoriatic arthritis patients has been demonstrated in several placebo controlled and open label trials, but the high cost and potential risks associated with the anti-tumor necrosis factor-α (TNF-α) agent warrants careful selection of patients who are most likely to benefit from this treatment, wrote Dr. Jordi Gratacós of Parc Taulí University Hospital in Barcelona, and colleagues.

To this end, the investigators sought to identify variables associated with a good clinical response in psoriatic arthritis patients being treated with the drug (Ann. Rheum. Dis. 2007 Jan. 25 [Epub doi: 10.1136/ard.2006.060079]).

The multicenter study included 69 patients with active psoriatic arthritis who showed no clinically significant response to at least 8 weeks of treatment with 15 mg of methotrexate weekly. Per study criteria, patients had to have peripheral polyarthritis—defined by the presence of five or more swollen and tender joints—and at least one of the following criteria: morning stiffness lasting more than 45 minutes, an erythrocyte sedimentation rate (ESR) of more than 30 mm per first hour, or a C-reactive protein (CRP) level greater than 15 mg/L. Patients testing positive for rheumatoid factor were excluded from the investigation.

In addition to their stable doses of methotrexate, study participants received 5mg/kg of inifliximab every 8 weeks.

In an intent-to-treat analysis conducted at 38 weeks of active treatment, 30 of the 69 patients (44%) experienced a major clinical response, defined as an improvement of at least 50% of the initial American College of Rheumatology (ACR) composite index, the authors reported. With use of the ACR20 and ACR70 measures, 44 and 18 patients, respectively, were identified as responders.

The results of a univariate analysis based on an ACR50 response at 38 weeks as the main outcome showed that involvement of large joints (hip or knee) and a high level of disability, defined as a score of 2 or higher on the validated Health Assessment Questionnaire (HAQ) at the start of treatment “were both predictors of smaller response to infliximab than in patients with no involvement of the large joints and an HAQ less than 2,” the authors wrote.

When the univariate analysis was performed at 14 weeks, the results were similar except for associations with CRP and age.

In the 14-week analysis, the presence of a CRP of at least 10 mg/L at the start of treatment “was associated with a significantly high rate of response,” reported the authors. And patients who achieved an ACR50 were younger (mean age 39 years), compared with those who did not respond (mean age 45 years), they wrote.

In a multivariate logistic regression model, CRP values and the absence of arthritis in the hip or knee or both were independent predictors of an ACR50 response.

Severe disability was not a significant predictor, but there was a trend toward an association, the authors reported.

While the results of this study suggest that some variables may significantly influence the treatment response to infliximab among patients with psoriatic arthritis, “the data reported here cannot be used as a definitive guide for deciding which patients should be given anti-TNF treatment,” the authors stressed, noting the study's small size and focus on patients with the most severe and refractory disease usually seen in clinical practice. “Large studies supporting our data will be needed in order to prove our statistical model and to establish more accurately the predictive factors for clinical response to infliximab in patients with [psoriatic arthritis],” they concluded.

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