Baricitinib in CPPD - the BAPTIST Study

Summary

The aim of this clinical trial is to determine if baricitinib is effective in treating calcium pyrophosphate deposition disease (CPPD) in adults. The primary objective is to assess its impact on joint inflammation. The key questions the study seeks to answer are: * Can baricitinib reduce inflammation in affected joints? * Will baricitinib lead to changes in ultrasound findings, such as calcium crystal deposition and synovitis? Researchers will compare baricitinib to other treatments, including methylprednisolone, colchicine, hydroxychloroquine, and methotrexate with folic acid, for managing CPPD.

Timeline

Start

2025-01

Primary completion

2026-06

Completion

2027-01

Publications

• Background Krenn V, Morawietz L, Burmester GR, Kinne RW, Mueller-Ladner U, Muller B, Haupl T. Synovitis score: discrimination between chronic low-grade and high-grade synovitis. Histopathology. 2006 Oct;49(4):358-64. doi: 10.1111/j.1365-2559.2006.02508.x.
• Background Krenn V, Morawietz L, Haupl T, Neidel J, Petersen I, Konig A. Grading of chronic synovitis--a histopathological grading system for molecular and diagnostic pathology. Pathol Res Pract. 2002;198(5):317-25. doi: 10.1078/0344-0338-5710261.
• Background Kelly S, Humby F, Filer A, Ng N, Di Cicco M, Hands RE, Rocher V, Bombardieri M, D'Agostino MA, McInnes IB, Buckley CD, Taylor PC, Pitzalis C. Ultrasound-guided synovial biopsy: a safe, well-tolerated and reliable technique for obtaining high-quality synovial tissue from both large and small joints in early arthritis patients. Ann Rheum Dis. 2015 Mar;74(3):611-7. doi: 10.1136/annrheumdis-2013-204603. Epub 2013 Dec 13.
• Background Sirotti S, Terslev L, Filippucci E, Iagnocco A, Moller I, Naredo E, Vreju FA, Adinolfi A, Becce F, Hammer HB, Cazenave T, Cipolletta E, Christiansen SN, Delle Sedie A, Diaz M, Figus F, Mandl P, MacCarter D, Mortada MA, Mouterde G, Porta F, Reginato AM, Schmidt WA, Serban T, Wakefield RJ, Zufferey P, Sarzi-Puttini P, Zanetti A, Damiani A, Pineda C, Keen HI, D'Agostino MA, Filippou G; OMERACT Ultrasound working group-CPPD subgroup. Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level. Lancet Rheumatol. 2023 Aug;5(8):e474-e482. doi: 10.1016/S2665-9913(23)00136-4. Epub 2023 Jul 5.
• Background Terslev L, Naredo E, Aegerter P, Wakefield RJ, Backhaus M, Balint P, Bruyn GAW, Iagnocco A, Jousse-Joulin S, Schmidt WA, Szkudlarek M, Conaghan PG, Filippucci E, D'Agostino MA. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 2: reliability and application to multiple joints of a standardised consensus-based scoring system. RMD Open. 2017 Jul 11;3(1):e000427. doi: 10.1136/rmdopen-2016-000427. eCollection 2017.
• Background Uson J, Rodriguez-Garcia SC, Castellanos-Moreira R, O'Neill TW, Doherty M, Boesen M, Pandit H, Moller Parera I, Vardanyan V, Terslev L, Kampen WU, D'Agostino MA, Berenbaum F, Nikiphorou E, Pitsillidou IA, de la Torre-Aboki J, Carmona L, Naredo E. EULAR recommendations for intra-articular therapies. Ann Rheum Dis. 2021 Oct;80(10):1299-1305. doi: 10.1136/annrheumdis-2021-220266. Epub 2021 May 25.
• Background Genovese MC, Smolen JS, Takeuchi T, Burmester G, Brinker D, Rooney TP, Zhong J, Daojun M, Saifan C, Cardoso A, Issa M, Wu WS, Winthrop KL. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2020 Jun;2(6):e347-e357. doi: 10.1016/S2665-9913(20)30032-1.
• Background Caporali R, Taylor PC, Aletaha D, Sanmarti R, Takeuchi T, Mo D, Haladyj E, Bello N, Zaremba-Pechmann L, Fang Y, Dougados M. Efficacy of baricitinib in patients with moderate-to-severe rheumatoid arthritis up to 6.5 years of treatment: results of a long-term study. Rheumatology (Oxford). 2024 Oct 1;63(10):2799-2809. doi: 10.1093/rheumatology/keae012.
• Background Filippou G, Adinolfi A, Cimmino MA, Scire CA, Carta S, Lorenzini S, Santoro P, Sconfienza LM, Bertoldi I, Picerno V, Di Sabatino V, Ferrata P, Galeazzi M, Frediani B. Diagnostic accuracy of ultrasound, conventional radiography and synovial fluid analysis in the diagnosis of calcium pyrophosphate dihydrate crystal deposition disease. Clin Exp Rheumatol. 2016 Mar-Apr;34(2):254-60. Epub 2016 Feb 9.
• Background Abhishek A, Tedeschi SK, Pascart T, Latourte A, Dalbeth N, Neogi T, Fuller A, Rosenthal A, Becce F, Bardin T, Ea HK, Filippou G, Fitzgerald J, Iagnocco A, Liote F, McCarthy GM, Ramonda R, Richette P, Sivera F, Andres M, Cipolletta E, Doherty M, Pascual E, Perez-Ruiz F, So A, Jansen TL, Kohler MJ, Stamp LK, Yinh J, Adinolfi A, Arad U, Aung T, Benillouche E, Bortoluzzi A, Dau J, Maningding E, Fang MA, Figus FA, Filippucci E, Haslett J, Janssen M, Kaldas M, Kimoto M, Leamy K, Navarro GM, Sarzi-Puttini P, Scire C, Silvagni E, Sirotti S, Stack JR, Truong L, Xie C, Yokose C, Hendry AM, Terkeltaub R, Taylor WJ, Choi HK. The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease. Ann Rheum Dis. 2023 Oct;82(10):1248-1257. doi: 10.1136/ard-2023-224575. Epub 2023 Jul 26.
• Background Tedeschi SK, Huang W, Yoshida K, Solomon DH. Risk of cardiovascular events in patients having had acute calcium pyrophosphate crystal arthritis. Ann Rheum Dis. 2022 Aug 11;81(9):1323-1329. doi: 10.1136/annrheumdis-2022-222387.
• Background Kwan A, Ingrid E, Jiang M, Lim KKT. The cardiovascular risk of JAK inhibitors in treating rheumatic diseases. Int J Rheum Dis. 2024 Aug;27(8):e15308. doi: 10.1111/1756-185X.15308. No abstract available.
• Background Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, Germino R, Menon S, Sun Y, Wang C, Shapiro AB, Kanik KS, Connell CA; ORAL Surveillance Investigators. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med. 2022 Jan 27;386(4):316-326. doi: 10.1056/NEJMoa2109927.
• Background Damart J, Filippou G, Andres M, Cipolletta E, Sirotti S, Carboni D, Filippucci E, Diez P, Abhishek A, Latourte A, Ea HK, Ottaviani S, Letarouilly JG, Desbarbieux R, Graf S, Norberciak L, Richette P, Pascart T. Retention, safety and efficacy of off-label conventional treatments and biologics for chronic calcium pyrophosphate crystal inflammatory arthritis. Rheumatology (Oxford). 2024 Feb 1;63(2):446-455. doi: 10.1093/rheumatology/kead228.
• Background Zhang W, Doherty M, Pascual E, Barskova V, Guerne PA, Jansen TL, Leeb BF, Perez-Ruiz F, Pimentao J, Punzi L, Richette P, Sivera F, Uhlig T, Watt I, Bardin T. EULAR recommendations for calcium pyrophosphate deposition. Part II: management. Ann Rheum Dis. 2011 Apr;70(4):571-5. doi: 10.1136/ard.2010.139360. Epub 2011 Jan 20.
• Background T Virtanen A, Haikarainen T, Raivola J, Silvennoinen O. Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases. BioDrugs. 2019 Feb;33(1):15-32. doi: 10.1007/s40259-019-00333-w.
• Background Guerne PA, Terkeltaub R, Zuraw B, Lotz M. Inflammatory microcrystals stimulate interleukin-6 production and secretion by human monocytes and synoviocytes. Arthritis Rheum. 1989 Nov;32(11):1443-52. doi: 10.1002/anr.1780321114.
• Background Punzi L, Oliviero F, Ramonda R. Transforming growth factor-beta levels in synovial fluid of osteoarthritis with or without calcium pyrophosphate dihydrate crystals. J Rheumatol. 2003 Feb;30(2):420; author reply 420-1. No abstract available.
• Background Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006 Mar 9;440(7081):237-41. doi: 10.1038/nature04516. Epub 2006 Jan 11.

Drugs

Indications