Mycophenolate for persistent complex regional pain syndrome, a parallel, open, randomised, proof of concept trial.

ABSTRACT

BACKGROUND AND AIMS: Current therapies for persistent complex regional pain syndrome (CRPS) are grossly inadequate. With accruing evidence to support an underlying immunological process and anecdotal evidence suggesting potential efficacy of mycophenolate, we wished to explore the feasibility and effectiveness of this treatment in patients with CRPS. METHODS: A randomised, open, parallel, proof of concept trial was conducted. Patients with Budapest research criteria CRPS of >2-year duration and moderate or high pain intensity (numeric rating scale score ≥5) were enrolled. Eligible patients were randomised 11 to openly receive mycophenolate as add-on treatment, or their usual treatment alone, over 5.5 months. They then switched to the other treatment arm for 5.5 months. The main outcome was average the patients' average pain intensity recorded over 14 days, between 5.0 and 5.5 months post randomisation, on 11-point (0-10) numeric rating scales, compared between trial arms. Skin sensitivities and additional outcomes were also assessed. RESULTS: Twelve patients were enrolled. Nine provided outcomes and were analysed for the main outcome. Mycophenolate treatment was significantly more effective than control [drug-group mean (SD) pre 7.4 (1.2)- post 5.2 (1.3), n=4, control pre 7.7 (1.4)- post 8.1 (0.9), n=5; -2.8 (95% CI -4.7, -1.0), p=0.01, analysis of covariance]. There were four treatment responders (to mycophenolate treatment either before, or after switch), whose initial exquisite skin hyper-sensitivities, function and quality of life strongly improved. Side effects including itchiness, skin-cryptitis, increased pain, and increased depression caused 45% of the subjects to stop taking mycophenolate. CONCLUSIONS: Mycophenolate appears to reduce pain intensity and improve quality of life in a subgroup of patients with persistent CRPS. IMPLICATIONS These results support the feasibility of conducting a definite trial to confirm the efficacy and effect size of mycophenolate treatment for persistent CRPS (EudraCT 2015-000263-14).