ARTHRITIS & RHEUMATISM Vol. 56, No. 2, February 2007, pp 688–692 DOI 10.1002/art.22389 © 2007, American College of Rheumatology Methotrexate as an Alternative Therapy for Chronic Calcium Pyrophosphate Deposition Disease An Exploratory Analysis Ame ´lie Chollet-Janin, 1 Axel Finckh, 1 Jean Dudler, 2 and Pierre-Andre ´ Guerne 1 Objective. To evaluate the effectiveness of metho- trexate (MTX), which works not only as an immunosup- pressant, but also as a potent antiinflammatory agent, as an alternative therapeutic option for patients with severe calcium pyrophosphate deposition disease (CPDD) who fail to respond to standard therapy with nonsteroidal antiinflammatory drugs and/or glucocorti- coids. Methods. We analyzed, in 2 university hospitals in Switzerland, consecutive patients with CPDD that was resistant to classic treatment and were subse- quently treated with MTX. Before and after initiation of MTX therapy, we quantified the frequency of pseudo- gout attacks, pain intensity, the number of swollen and tender joints, and inflammatory biomarkers. Clinical and biologic side effects of MTX and patients satisfac- tion with MTX treatment were also evaluated. Results. The study included 5 patients treated with low dosages of MTX (5–20 mg/week). The mean followup time with MTX was 50.4 months (range 6–81 months). All patients reported an excellent clinical response, with marked improvement within a mean period of 7.4 weeks. A significant decrease in pain intensity (P < 0.0001), swollen and tender joint counts (P < 0.0001), and frequency of attacks was observed. The biomarkers of inflammation decreased markedly when systematically analyzed (3 patients). No signifi- cant side effects were reported. Conclusion. This study suggests that MTX could be a valuable therapeutic option for severe CPDD that is refractory to conventional therapy. Chondrocalcinosis, or calcium pyrophosphate deposition disease (CPDD), is a common and poten- tially severe metabolic arthropathy caused by calcium pyrophosphate dihydrate (CPPD) crystal deposition (1). CPDD is particularly frequent in the second half of life, with radiographic evidence in up to 5% of the human population and with the prevalence rising almost linearly to 15% over 60 years of age and 30–40% in those over 80 years of age (2). Although frequently asymptomatic, CPDD can cause severe acute attacks of inflammatory arthritis (pseudogout), mainly in the knees and wrists, as well as various forms of chronic, frequently destructive, arthropathies. CPDD can be divided into 3 main sub- types: a widespread but paucisymptomatic form resem- bling osteoarthritis, a type of rapidly destructive arthro- pathy, and a highly inflammatory chronic arthropathy that mimics rheumatoid arthritis (RA). The pathogenesis of inflammation due to CPDD is related to the recruitment, activation, and prolifera- tion of numerous cells, including polymorphonuclear neutrophils (PMNs), and the synthesis, expression, and secretion of abundant mediators of inflammation and/or catabolic enzymes. CPPD crystals have direct catabolic effects on cartilage and synovium, and thus, do not require inflammation for catabolism (1,3,4). No cur- rently available drug is known to prevent the progression of CPPD crystal deposition and gradual joint deteriora- tion. Treatment is therefore essentially symptomatic. Nonsteroidal antiinflammatory drugs (NSAIDs) and in- traarticular or systemic glucocorticoids are the main Dr. Finckh’s work was supported by a scholarship from the University of Geneva. 1 Ame ´lie Chollet-Janin, MD, Axel Finckh, MD, MS, Pierre- Andre ´ Guerne, MD, PD: University Hospital of Geneva, Geneva, Switzerland; 2 Jean Dudler, MD: University Hospital of Lausanne, Lausanne, Switzerland. Address correspondence and reprint requests to Pierre- Andre ´ Guerne, MD, PD, University Hospital of Geneva, Division of Rheumatology, 26 Avenue de Beau-Se ´jour, 1211 Geneva 14, Switzer- land. E-mail: pierre-andre.guerne@hcuge.ch. Submitted for publication June 20, 2006; accepted in revised form October 30, 2006. 688