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 alpha-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.

Fatigue in rheumatoid arthritis reflects pain, not disease activity.

OBJECTIVE: We determined the amount of fatigue experienced by patients with RA, and its relationship to synovitis, pain and other common clinical features. We also examined to what extent RA fatigue is improved by disease-modifying antirheumatic drugs (DMARDs) and anti-tumour necrosis factor (TNF) therapy. METHODS: We studied two cohorts of 238 and 274 RA patients cross-sectionally and examined treatment responses in 30 RA patients starting anti-TNF and 54 starting DMARDs followed for 3 and 6 months. We measured fatigue using visual analogue scores (VAS) and Medical Outcomes Study Short Form 36 (SF-36) vitality scores. We recorded the disease activity score for 28 joints and its components (tender/swollen joint counts, patient global assessment, ESR), morning stiffness, health assessment questionnaire, physician global assessment, erosive disease, nodules, rheumatoid factor, concomitant medications and illnesses, and the SF-36 questionnaire. RESULTS: Fatigue was common in RA patients; over 80% had clinically relevant fatigue (VAS > or =20 mm), over 50% had high levels (VAS > or =50 mm). It was associated with pain and changes in mental health, particularly depression. In each of the two cross-sectional cohorts, this relationship was similar whichever measures of fatigue and mental health were used. Fatigue fell with DMARDs and anti-TNF: before treatment, 87% of patients had high fatigue, after treatment this fell to 50%. These treatment effects were mainly linked to improvements in pain. CONCLUSIONS: High fatigue levels characterize RA and are mainly linked to pain and depression. The association with disease activity is secondary. Fatigue falls with DMARD and anti-TNF therapy. The balance of evidence suggests that fatigue is centrally mediated in established RA.