Calcium Pyrophosphate Deposition Disease Diagnosis & Treatment Gaps Remain

Dr. Pascart said the “exciting part” is targeted therapy in CPPD. A Nature study from 20 years ago showed CPP crystal formation involved the NALP3 inflammasone resulting in high interleuken 1 (IL-1). If you block that cytokine, you could also stop the huge production of IL-6.⁶

In 2020, Latourte and others undertook a pilot study looking at tolcizumab in CPPD. Those who had very refractory disease and had anakinra in their treatment improved using tolcilizumab.⁷

“This was a great promise to open doors in using biologics and particularly IL-6 inhibitors,” said Dr. Pascart. “Basically everyone seems to agree a trial of colchicine is the first line that should be proposed in all cases. When it fails or is not tolerated, you think of methotrexate and then biologics. We don’t now have enough evidence to support the use of hydrochloricone.”

The research is expanding. Two trials are ongoing comparing colchicine with placebo. One study is looking at toclizumab vs. placebo. A fourth is comparing baricitnib and usual care.

“In terms of management of CPPD disease, there is an urgent need for guidance,” said Dr. Pascart. “The only available recommendations are 15 years old from the European Alliance of Associations for Rheumatology with nothing from the ACR. I am not aware of any national recommendations either. Hopefully we’ll be able to formulate these in the next few years.”

Kurt Ullman is a freelance writer based in Indiana.

References

1. Cai K, Fuller A, Zhang Y, et. al. Towards development of core domain sets for short term and long term studies of calcium pyrophosphate crystal deposition (CPPD) disease: A framework paper by the OMERACT CPPD working group. Semin Athritis Rheum. 2024 Aug;51(4):946–950.
2. McCarty DJ. Calcium pyrophosphate dihydrate crystal deposition disease: Nomenclature and diagnostic criteria. Ann Intern Med. 1977 Aug;87(2):241–242.
3. Wu Y, Liew JW, Boer JD et. al. Chondocalcinosis and incident knee arthritis: findings from 2 large prospective cohorts with 20 year follow-up. Ann Rheum Dis. 2025 Oct;84(10):1743–1751.
4. Pascart T, Robinet P, Ottaviani S, et al. Evaluating the safety and short-term equivalence of cholchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): an open-label, multicentre, randomized trial. Lancet Rheumatol. 2023 Sept;5(9):e523–e531.
5. Pascart T, Norberciak L, Richette P, et. al. Exploring patient profiles associated with resolution of acute calcium pyrophosphate arthritis treated with colchicine and prednisone: post hoc analysis of a randomized controlled trial. Arthritis Care Research (Hoboken). 2025 Sept. Online ahead of print.
6. Martinon F, Petrill V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006 Mar 9;440(7081):237–241.
7. Latourte A, Ea HK, Frazier A, et. al. Tocilizumab in symptomatic calcium pyrophosphate deposition disease: A pilot study. Ann Rheum Dis. 2020 Aug;79(8):1126–1128.

Disclosures

Dr. Tedeschi is a consultant with Alexion, Avalo and Novartis, and was formerly a consultant with Merck/MSD. Dr. Pascart is a consultant with Avalo.