Background Calcium pyrophosphate deposition (CPPD) disease is a chronic arthropathy caused by calcium pyrophosphate (CPP) crystal formation and deposition in joints (1). It can be divided into different clinical subtypes: asymptomatic CPPD, osteoarthritis with CPPD, acute CPP crystal arthritis, and chronic CPP crystal inflammatory arthritis (2). In this latter form, colchicine (Co), nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids (GCs) are commonly used with good effects.Some unresponsive cases, however, need alternative pharmacological treatments. Some authors suggested that methotrexate (MTX) could represent a good option in refractory patients (3).
Objectives The aim of this study was to evaluate the effectiveness of MTX in patients with severe chronic CPP polyarthritis, who did not respond to NSAIDs and/or Co and GCs.
Methods Twenty one outpatients (11 male; mean age 63.38 ±5.27) with resistant chronic CPP arthritis, were treated with MTX in dose between 7.5–12.5 mg/week. All patients fulfilled the EULAR diagnostic criteria for CPPD (2). Tender (TJC) and swollen joints count (SJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed at baseline, before MTX initiation (M0), and at three, six and nine months (M3, M6, M9). Clinical and biologic side effects of MTX were evaluated. The statistical analysis was performed using Friedman with Dunn's Multiple Comparison Test.
Results At M0 the mean of TJC and SJC were 18.00±3.41 and 10.38±1.96, respectively. These parameters decreased considerably at M3 (TJC=9.62±2.52; SJC=7.95±2.84), reaching a significance at M6 (TJC=4.62±1.88; SJC=3.05±2.06) and at M9 (TJC=1.38±1.28;SJC=0.67±0.66) with respect to M0 (p<0.0001). These clinical features were associated to a significant improvement of ESR and CRP levels. The ESR decreased from 52.38±11.47 (M0) to 18.38±12.64 (M9) mm/hour (p<0.001) while CRP levels decreased from 3.00±1.27 (M0) to 0.28±0.22 (M9) mg/dl (p<0.0001). No relevant side biological and clinical effects were reported. No patients interrupted or reduced the dose of MTX.
Conclusions This study confirms that MTX is a valid therapeutic alternative in severe chronic CPP arthritis patients, refractory to previous conventional drugs. According to this study, we observed an excellent response, with a good safety profile. Further additional studies are necessary to expanding the knowledge and identifying the patients in which MTX could be effective.
Johnson K, Terkeltaub R. Inorganic pyrophosphate (PPI) in pathologic calcification of articular cartilage. Front Biosci 2005;10:988–97
Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis 2011;70 563–70
Andreas M, Sivera F, Pascual E. Methotrexate is an option for patients with refractory calcium pyrophosphate crystal arthrytis. J Clin Rheumatol 2012;18:234–6
Disclosure of Interest None declared
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