Methotrexate in chronic-recurrent calcium pyrophosphate deposition disease: no significant effect in a randomized crossover trial

Abstract

Introduction: Calcium pyrophosphate deposition (CPPD) may cause severe arthropathy, major joint destruction and treatment options are limited. The aim of this study was to test the therapeutic efficacy of methotrexate (MTX) in chronic or recurrent CPPD arthropathy.

Methods: Patients with CPPD arthropathy were randomized to receive either weekly subcutaneous injections of 15 mg/week of MTX or placebo (PBO) for three months, in a double-blind, crossover randomized controlled trial. Inclusion criteria comprised definite CPPD disease, recurrent arthritis or persistent polyarthritis, and an insufficient response to NSAIDs, glucocorticoids or colchicine. The primary outcome was an improvement in the disease activity scores based on 44 joints (DAS44). The analysis was performed on an intent-to-treat basis.

Results: We randomized 26 patients, and compared 25 treatment periods on MTX with 21 treatment periods on PBO. Baseline characteristics were balanced between the groups. The evolution of the DAS44 was not statistically significantly different between groups (median DAS44 decreased by -0.08 on MTX versus -0.13 on PBO, after three months, P = 0.44). Furthermore, pain levels remained stable in both groups (median change in VAS Pain -1 unit on MTX and 0 on PBO, P = 0.43), and none of the secondary outcomes was significantly different between the two groups. Minor adverse events (AE) did not differ in frequency between the groups, but the only serious AE occurred on MTX (bicytopenia).

Conclusions: The results of this trial with MTX in this older population with chronic or recurrent CPPD arthropathy suggest no strong effect of MTX on disease activity.

Trial registration: EudraCT No: 2007-003479-37. Registered 26 April 2008.

Figure 1

Study design. This was a double-blind, crossover randomized controlled trial. Patients were randomized to receive either methotrexate (MTX) or placebo (PBO) during an initial treatment period of three months, followed by a ‘wash-out’ phase of two months and a crossover second treatment period of three months. The T + X (↓) represent monthly assessments since randomization; the status (↑) represent medical visits with a clinical examination.

Figure 2

Flow diagram of the study. Displays the study flow: 49 patients were screened, 26 corresponded to the inclusion and exclusion criteria and signed the study informed consent form, 21 (81%) finished the first treatment period and 20 (95%) the second treatment period. Overall, 25 patients completed the methotrexate (MTX) treatment period and 21 the placebo (PBO) treatment period.

Figure 3

Evolution in disease activity. Displays the evolution of the disease activity as measured by the disease activity score based on 23 joints (DAS28) while receiving either methotrexate (MTX) (N = 25) or placebo (PBO) (N = 21). This figure aggregates both treatment periods, before and after the crossover.