AB1251 PROGNOSIS OF ESSENTIAL MIXED CRYOGLOBULINEMIA AND CONNECTIVE TISSUE DISEASE-RELATED CRYOGLOBULINEMIA AFTER RITUXIMAB-INDUCED REMISSION
Authors: C. Poggi, E. Hachulla, A. Karras, A. Briantais, C. Ravaiau, P. Gobert, A. Deroux, S. Nicolas, H. François, M. Groh, J. London, J. Campagne, J. S. Allain, E. Dernis, C. A. Durel, T. Le Gallou, A. Curie, P. Kerschen, N. Gensous, A. H. Reboux, H. Béhal, B. Terrier, T. Quéméneur
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The treatment and prognosis of cryoglobulinemia vasculitis (CryoVas) depend on etiology. Rituximab (RTX) and corticosteroids (CS) are the first line treatment for mixed essential (ME) CryoVas and connective tissue disease (CTD)-related CryoVas. The prognosis and long term outcomes of these forms of CryoVas are as yet unknown. <h3>Objectives:</h3> The aim of this study was therefore to describe the risk of relapse and treatment-related morbidities in patients with ME and CTD-related CryoVas. <h3>Methods:</h3> A retrospective study was conducted of 63 patients in remission of ME or CDT-related CryoVas after RTX-CS therapy, with a median follow-up time of 58 months (interquartile range, 33–88 months). <h3>Results:</h3> Thirty-nine out of 63 patients (62%) had a relapse a median of 42 (23–65) months after the initial flare. The relapse incidence was 38% at 2 years and 46% at 3 years. The factors associated with relapse were purpura at the time of the qualifying flare (HR, 2.2; 95% confidence interval (CI), 1.1–4.4; <i>p</i> = 0.002) and prior history of CryoVas flares (HR, 1.9; 95% CI, 1.0–3.7; <i>p</i> = 0.04). Maintenance therapy was associated with a lower risk of relapse 6–24 months after the initial flare (HR, 0.27; 95% CI, 0.09–0.78; <i>p</i> = 0.02), but not thereafter (HR, 2.0; 95% CI, 0.7–5.7; <i>p</i> = 0.21). The most common form of maintenance therapy was 500 mg RTX every 6 months. The most frequent complication was infection, and maintenance RTX therapy was associated with a higher risk of severe infection (HR, 2,2; 95% CI, 0.9–5,6; <i>p</i> = 0.08). <h3>Conclusion:</h3> In this group of patients in RTX-CS remission of ME and CTD-related CryoVas, relapses were common and the risk of relapse was significantly associated with purpura during the qualifying flare and a prior history of relapse. Maintenance RTX was associated with a lower risk of relapse but was also associated with an increased risk of severe infection. <h3>REFERENCES:</h3> [1] Saadoun D, Sellam J, Ghillani-Dalbin P, Crecel R, Piette JC, Cacoub P. Increased Risks of Lymphoma and Death Among Patients With Non–Hepatitis C Virus–Related Mixed Cryoglobulinemia. Arch Intern Med. 2006 Oct 23;166(19):2101–8. [2] Cacoub P, Comarmond C, Domont F, Savey L, Saadoun D. Cryoglobulinemia Vasculitis. Am J Med. 2015 Sep 1;128(9):950–5. [3] Terrier B, Krastinova E, Marie I, Launay D, Lacraz A, Belenotti P, et al. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey. Blood. 2012 Jun 21;119(25):5996–6004. [4] Terrier B, Carrat F, Krastinova E, Marie I, Launay D, Lacraz A, et al. Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey. Ann Rheum Dis. 2013 Mar 1;72(3):374–80. [5] Quartuccio L, Bortoluzzi A, Scirè CA, Marangoni A, Del Frate G, Treppo E, et al. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC). Clin Rheumatol. 2023 Feb 1;42(2):359–70. [6] Terrier B, Marie I, Launay D, Lacraz A, Belenotti P, de Saint-Martin L, et al. Predictors of early relapse in patients with non-infectious mixed cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey. Autoimmun Rev. 2014 Jun 1;13(6):630–4. [7] Foessel L, Besancenot JF, Blaison G, Magy-Bertrand N, Jaussaud R, Etienne Y, et al. Clinical Spectrum, Treatment, and Outcome of Patients with Type II Mixed Cryoglobulinemia without Evidence of Hepatitis C Infection. J Rheumatol. 2011 Apr 1;38(4):716–22. [8] Visentini M, Tinelli C, Colantuono S, Monti M, Ludovisi S, Gragnani L, et al. Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: Phase II clinical trial and systematic review. Autoimmun Rev. 2015 Oct;14(10):889–96. [9] Colantuono S, Mitrevski M, Yang B, Tola J, Carlesimo M, De Sanctis GM, et al. Efficacy and safety of long-term treatment with low-dose rituximab for relapsing mixed cryoglobulinemia vasculitis. Clin Rheumatol. 2017 Mar 1;36(3):617–23. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Claire POGGI: None declared, Eric Hachulla BOEHRINGER INGELHEIM, GSK, SANOFI,, JANSSEN-CILAG, Bayer HealthCare SAS, GSK, BRISTOL MYERS SQUIBB, IQVIA Operations France, United Therapeutics Corporation, NOVARTIS PHARMA SAS, CHUGAI PHARMA FRANCE, ASTRAZENECA, MSD, JANSSEN-CILAG, Bayer HealthCare SAS, GSK, BRISTOL MYERS SQUIBB,, GENZYME, SANOFI, RE-IMAGINE Health Agency, Otsuka Pharmaceutical France SAS, AXONAL, PFIZER SAS, LIVE! BY GL EVENTS, SHIRE France S.A., Cemka, ROCHE SAS, Galapagos SASU, PATIENTYS, Alexandre Karras Alnylam France SAS, BOEHRINGER INGELHEIM FRANCE, NOVARTIS PHARMA SAS, ASTRAZENECA, Otsuka Pharmaceutical France SAS, LABORATOIRE GLAXOSMITHKLINE, PFIZER SAS, Vertex Pharmaceuticals Incorporated, TRAVERE THERAPEUTICS, INC., Retrophin, Inc, Antoine BRIANTAIS BOEHRINGER INGELHEIM FRANCE,, ROCHE SAS, LABORATOIRE GLAXOSMITHKLINE, Genzyme, Camille Ravaiau: None declared, Pierre GOBERT Alexion Pharma France, MENARINI FRANCE, SANOFI AVENTIS FRANCE, Alban Deroux VIFOR FRANCE, EUSA Pharma (France) SAS, BOEHRINGER INGELHEIM FRANCE, LABORATOIRE GLAXOSMITHKLINE, SANOFI AVENTIS FRANCE, EXELTIS SANTE, Celltrion Healthcare France SAS, SWEDISH ORPHAN BIOVITRUM, Sarah Nicolas HD MEDICAL, MSD FRANCE, Hélène François SANOFI AVENTIS FRANCE,, Matthieu Groh SANOFI AVENTIS FRANCE, LABORATOIRE GLAXOSMITHKLINE, ASTRAZENECA, CSL BEHRING SA, CHUGAI PHARMA FRANCE, BRISTOL-MYERS SQUIBB, Jonathan London AMICUS THERAPEUTICS SAS, CORIN FRANCE, AMICUS THERAPEUTICS SAS, CORIN FRANCE, JANSSEN-CILAG, AbbVie, Julien Campagne SHIRE France S.A., SANOFI AVENTIS FRANCE,, BOEHRINGER INGELHEIM FRANCE,, VIFOR FRANCE SA, SANDOZ, Alnylam France SAS, AMGEN, Jean-Sébastien Allain LEO Pharma, LABORATOIRE GLAXOSMITHKLINE, Emmanuelle Dernis BRISTOL-MYERS SQUIBB, LILLY FRANCE, MSD France, JANSSEN-CILAG, Galapagos SASU, AbbVie, NORDIC PHARMA SAS, UCB Pharma SA, CHUGAI PHARMA FRANCE, FRESENIUS KABI FRANCE, MSD France, BRISTOL-MYERS SQUIBB,, NOVARTIS PHARMA SAS, AMGEN SAS, MEDAC SAS, RE-IMAGINE Health Agency, Cécile-Audrey Durel VIFOR FRANCE, NOVARTIS PHARMA SAS, Genzyme, NOVARTIS PHARMA SAS, Genzyme, Takeda France, SHIRE France S.A., BOEHRINGER INGELHEIM FRANCE, Thomas Le Gallou NOVARTIS PHARMA SAS, LABORATOIRE GLAXOSMITHKLINE, Alexandre Curie PFIZER SAS, LABORATOIRE GLAXOSMITHKLINE, SHIRE France S.A., Philippe Kerschen: None declared, Noémie Gensous Alnylam France SAS, SWEDISH ORPHAN BIOVITRUM, NOVARTIS PHARMA SAS, AMGEN SAS, ASTRAZENECA, AMGEN SAS, Anne-Hélène Reboux: None declared, Hélène Béhal: None declared, Benjamin Terrier VIFOR, ASTRAZENECA, GSK, ASTRAZENECA, LFB BIOMEDICAMENTS, BRISTOL-MYERS SQUIBB, PFIZER SAS, Lilly France SAS, GRIFOLS France, Oséus, Terumo BCT Europe SA, SANOFI-AVENTIS RECHERCHE &amp; DEVELOPPEMENT, BOEHRINGER INGELHEIM FRANCE, FRESENIUS KABI FRANCE, SWEDISH ORPHAN BIOVITRUM, BRISTOL-MYERS SQUIBB, NOVARTIS PHARMA SAS, ROCHE SUISSE, JANSSEN-CILAG, MSD France, RE-IMAGINE Health Agency, LFB BIOMEDICAMENTS, Thomas Quéméneur VIFOR, LEO Pharma, ASTRAZENECA, VIFOR, OVERCOME,, VIFOR, SANOFI, GENZYME, GSK.