Louise C. Pollard

Rheumatoid arthritis: non-tumor necrosis factor targets.

Purpose of reviewThe treatment of rheumatoid arthritis has been revolutionised in recent years with the advent of biologic treatments. The purpose of this review is to outline new treatments that target the inflammatory pathway in rheumatoid arthritis other than tumor necrosis factor-α. Recent findingsAs the use of anti-tumor necrosis factor-α treatment has become more widespread, the number of patients in whom this treatment is unsuccessful has also accumulated. Contraindications such as infection and cardiac failure further add to the number of patients who need alternative treatment. A better understanding of the inflammatory pathway in rheumatoid arthritis has led to interest in other therapeutic targets. Promising treatments such as interleukin-6 antagonists (MRA), CTLA4Ig (abatacept), and anti-B cell therapy (rituximab) have already been tested in randomized controlled trials over the past year. Other cytokines have been identified and have been shown to be of benefit in animal models, including interleukin-15, interleukin-17, and interleukin-18, and clinical trials of these agents are currently under way. SummaryFor patients with rheumatoid arthritis that does not respond to anti-tumor necrosis factor-α treatment, the promising alternatives MRA, abatacept, and rituximab have been tested. It is hoped that these agents will become available shortly.

Pain Thresholds in Rheumatoid Arthritis: The Effect of Tender Point Counts and Disease Duration

Objective. We evaluated the influence of demographic and clinical factors on pain thresholds in patients with rheumatoid arthritis (RA). Methods. A cross-sectional observational study (105 patients with RA) assessed pain thresholds using an algometer. Regression analysis examined the influence of demographic and clinical assessments. Results. Pain thresholds (median 289, interquartile range 89–434) correlated with assessments of disease activity (tender joint counts), disability (Health Assessment Questionnaire), fatigue, depression, and anxiety. Ordinal logistic regression showed tender point counts and disease duration were the dominant contributors. Conclusion. These findings suggest that low pain thresholds reflect “fibromyalgic” RA (many tender points) and central pain sensitization with prolonged disease duration.

A Randomised double-blind, placebo-controlled trial of a recombinant version of human alpha fetoprotein (MM-093) in patients with active rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of α-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinant version of human AFP. Objective: To assess the safety, tolerability and clinical effects of MM-093 during a 12-week, randomised, double-blind, placebo-controlled study. Methods: 12 patients with RA, who had active disease and were on stable doses of methotrexate, received weekly subcutaneous injections of placebo or 21 mg of MM-093. Assessments were carried out at baseline and weekly thereafter. Results: Baseline characteristics were similar in both groups. There was one dropout in the placebo group, due to flare of disease. Treatment with MM-093 was well tolerated. No serious adverse event was observed. By day 85, MM-093 produced a significant mean improvement from baseline in Disease Activity Score 28 (DAS28; 0.913 vs 0.008, p = 0.033) and patient’s global assessment (28.9% vs −36.3%, p = 0.02) compared with placebo. Conclusion: This is the first randomised, controlled trial of MM-093, a recombinant version of human AFP, in patients with RA. MM-093 was well tolerated. Evidence of efficacy was observed, suggesting that MM-093 may have therapeutic potential in RA.