Efficacy of anakinra for refractory acute calcium pyrophosphate crystal arthritis

Acute synovitis induced by deposition of calcium pyrophosphate (CPP) and monosodium urate crystals involves interleukin-1β production and activation. The efficacy of blocking interleukin-1β activity (with an interleukin-1 receptor antagonist [anakinra] or interleukin-1β antibody) is well documented for gout attacks but has only been reported in two single-case reports of CPP crystal-induced acute arthritis. Here we report on five cases (four males, mean age 71±27) of CPP crystal-induced inflammatory arthritis refractory and/or intolerant to usual drug therapy and efficiently treated with anakinra. Diagnosis of CPP crystal-induced arthritis was confirmed by identification of crystals in synovial fluid. CPP crystal-induced oligo-arthritis (n=4) and polyarthritis (n=1) were refractory to conventional treatments, including non-steroidal anti-inflammatory drugs, colchicine and steroids (systemic administration or intra-articular injection). After latent infection was ruled out, anakinra, 100mg/day, was administered subcutaneously for 3 days. Four patients showed rapid clinical and biological responses at a mean of 3 days after treatment. Anakinra provided good joint pain relief (baseline 0-100mm visual analog scale score 60±17mm, outcome 10±10mm) and decreased serum C-reactive protein level (58±43 to 5±2mg/L). Anakinra was well tolerated. One injection-site skin reaction was observed but no infection. Anakinra was effective and safe in this small series of patients with refractory arthritis due to acute CPP crystal deposition.