Background/Purpose:   Calcium pyrophosphate crystal-induced arthritis (CPPD) is an acute crystal arthritis, frequently involving the wrist or the knee. Monosodium urate in gout or CPPD in pseudogout have been shown to trigger the release of IL-1β, a strong pro-inflammatory cytokine, through a complex intracellular molecular cascade. IL-1 blockade showed efficacy in treating acute gouty arthritis in phase 3 controlled studies, and there are published retrospectives series and case reports showing a good clinical response in CPPD arthritis in blocking IL-1 with anakinra, an IL-1 receptor antagonist. This randomized controlled trial was designed to evaluate the efficacy and safety of anakinra versus prednisone to treat acute CPPD arthritis.

Methods:   Single center, randomized, double blinded controlled study. ISRCTN registration number: ISRCTN46471047. Patients presenting, between 2012 and 2015, with an acute CPPD arthritis (< 5 days duration), were randomly assigned in a 1:1 ratio to a treatment of anakinra 100 mg s.c. + placebo matching prednisone or prednisone 30 mg + placebo matching anakinra s.c. for 3 days. Acute CPPD arthritis was defined as presence of clinical symptoms and CPPD crystals in joint fluid aspiration at screening or in the medical history. Primary outcome was the pain evaluation at 72 hours post dose on a 0-100 mm VAS scale. Secondary outcomes were assessments by the patient and physician of pain intensity and global response over a 28 days period.

Results: Fifteen patients were randomized, 8 assigned to anakinra and 7 assigned to prednisone treatment. Baseline characteristics of both groups were comparable. Three patients (2 in the anakinra group and 1 in the prednisone group) presented a flare 2 weeks after the intervention and were excluded from the study, treated with medication not allowed by the protocol (including open label treatment with anakinra for 1 patient). The study was stopped after 3 years due to a persistent low inclusion rate, reaching only 30% of the 50 expected randomized patients, mainly linked to the short requested delay of symptoms duration for inclusion. Pain reduction at 72 hours on a VAS scale compared with baseline was statistically significant in the anakinra group (-39 mm, p=0.02) but not statistically significant in the prednisone group (-23 mm, p=0.07). There was no statistically significant difference between both groups concerning the primary outcome. All other outcome measures were in favour of the anakinra group, but without being statistically significant due to an underpowered study. No serious adverse events were observed in both groups.

Conclusion:   Both anakinra and prednisone seem to be effective in the treatment of acute CPPD-induced arthritis and we observed a trend in favour of anakinra, but non statistically significant, due to an underpowered study. More prospective randomized controlled trials are needed with more patients, probably with a multicentric design.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anakinra-compared-to-prednisone-on-the-treatment-of-acute-cppd-crystal-arthritis-a-randomized-controlled-double-blind-study/