Mycophenolate Mofetil Use in Clinical Practice: Persistence on Therapy and Long-term Adverse Events in a Multicentric Cohort of Scleroderma Patients

Silvia Bosello¹, enrico De Lorenzis¹, lucrezia verardi¹, gerlando Natalello¹, pier giacomo Cerasuolo¹, Stefano Di Donato², Greta Pellegrino³, Giacomo De Luca⁴, Corrado Campochiaro⁵, Gemma Lepri⁶, Laura Cometi⁷, Fabio Cacciapaglia⁸, Giuseppe Armetano⁹, Marco De Pinto¹⁰, Francesca Motta¹¹, Maria De Santis¹¹, Dilia Giuggioli¹², Nicoletta Del Papa⁹, Florenzo Iannone¹³, Serena Guiducci⁷, valeria Riccieri¹⁴, Maria Antonietta D'Agostino¹ and Francesco Del Galdo², ¹Division of Rheumatology - Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy, ²University of Leeds - Leeds Institute of Rheumatic and Muskuloskeletal Medicine, Leeds, United Kingdom, ³Department of Rheumatology, La Sapienza University of Rome, Rome, Italy, ⁴Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milano, Italy, ⁵IRCCS San Raffaele Hospital, Unit of Immunology, Rheumatology, Allergy and Rare Disease. Vita-Salute San Raffaele University, Milan, Italy, ⁶Department of Experimental and Clinical medicine, Division of Rheumatology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy, ⁷University of Florence, Unit of Rheumatology Azienda Ospedaliera Careggi, Florence, Italy, ⁸Rheumatology Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari, Bari, Italy, ⁹Scleroderma Clinic, Dipartimento di Reumatologia, ASST Gaetano Pini CTO, Milano, Italy, ¹⁰Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Modena, Italy, ¹¹Reumatologia e Immunologia Clinica, IRCCS Humanitas Research Hospital, Humanitas University, Rozzano, Milan, Italy, ¹²Scleroderma Unit, Rheumatology Unit, University Hospital of Modena and Reggio Emilia, Modena, Italy, ¹³Rheumatology Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy, ¹⁴Department of Clinical, Internal and Cardiovascular Specialities, Sapienza University of Rome, Roma, Italy

Meeting: ACR Convergence 2023

Keywords: Drug toxicity, Infection, Systemic sclerosis

Session Information

Date: Monday, November 13, 2023

Title: (1513–1533) Systemic Sclerosis & Related Disorders – Clinical Poster II: Clinical Trial, Treatment & Intervention

Session Type: Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Mycophenolate mofetil (MMF) is a first-line immunosuppressant treatment for systemic sclerosis (SSc), particularly for patients with interstitial lung disease (ILD) and diffuse skin involvement. MMF persistence reflects its efficacy, the risk or occurrence of adverse events (AEs), the risk of relapse after discontinuation, and the availability of therapeutic alternatives. Real-life evidence about early and long-term adverse events (AEs) associated with the use of MMF in SSc is lacking, and predictors of drug discontinuation are not identified yet. We aimed to investigate a) the incidence and causes of MMF discontinuation due to AEs in SSc patients and b) the incidence and association of severe infections, lower airway infections, and unbearable gastrointestinal symptoms leading to MMF discontinuation.

Methods: Medical records of SSc patients treated with MMF from January 2012 to December 2021 and followed up in 9 tertiary centers were retrospectively collected and evaluated. Clinical and demographic data included AEs (i.e., infections, gastrointestinal (GI) intolerance, laboratory abnormalities, new cancer diagnosis) and reasons for dosage reduction or discontinuation. Infection severity was ranked according to the GREFIG study classification system. A competing risk analysis was performed to explore the association of AE-related MMF discontinuations with alternative causes of MMF discontinuation as a competing risk.

Results: Data from 545 SSc patients observed for 3.1 years (IQR 1.4-4.9) were analyzed. Combination therapy with steroids was recorded in 37.0% of patients, while in 14.7% of cases, MMF was associated with additional immunosuppressants. Almost 25% of patients did not tolerate the prescribed dose of MMF because of drug-related AEs. MMF discontinuation rate was 6.6/1000 patients-year (95% IC 5.3-8.0) with a 70.3% 5-year retention rate (95% IC 0.65-0.76). Gastrointestinal intolerance and infections (GREFIG grades 2-3) were the most common AEs leading to discontinuation with different time patterns. Infection severity tended to increase over time. Respiratory infections were the most commonly reported infections. The risk of major infections (grades 2-3) was associated with male gender (HR 1.9, 95% IC 1.3-2.9), anti-centromere antibody (HR 1.7, 1.1-2,6), pulmonary hypertension (HR 2.0, 95% IC 1.3-3.0), late capillaroscopy pattern (HR 1.5, 95% IC 1.0-2.3), and concomitant COPD (HR 3.0, 95% IC 1.4-6.4) at univariate analysis.

Conclusion: One in four SSc patients had to reduce or discontinue MMF due to adverse events, primarily gastrointestinal intolerance and infections. Factors linked with microvascular impairment served as a risk factor for severe infections during MMF treatment.

Disclosures: S. Bosello: None; e. De Lorenzis: None; l. verardi: None; g. Natalello: None; p. Cerasuolo: None; S. Di Donato: None; G. Pellegrino: None; G. De Luca: Boehringer Ingelheim, 6, Janssen, 6, SOBI, 6; C. Campochiaro: Boehringer Ingelheim, 1, 6, Janssen, 1, 6, Novartis, 1, 6; G. Lepri: None; L. Cometi: None; F. Cacciapaglia: None; G. Armetano: None; M. De Pinto: None; F. Motta: None; M. De Santis: None; D. Giuggioli: None; N. Del Papa: None; F. Iannone: Abbvie, 2, 5, BMS, 2, 5, Janssen, 2, 5, Lilly, 2, 5, MSD, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, Roche, 2, 5, UCB, 2, 5; S. Guiducci: None; v. Riccieri: None; M. D'Agostino: AbbVie/Abbott, 2, 5, 6, Amgen, 2, 5, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, Celgene, 2, 5, 6, Eli Lilly, 2, 5, 6, Janssen, 2, 5, 6, Merck/MSD, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, UCB, 2, 5, 6; F. Del Galdo: AbbVie/Abbott, 5, arxx, 2, AstraZeneca, 2, 5, Boehringer-Ingelheim, 2, 5, capella, 2, Chemomab, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Mitsubishi-Tanabe, 2, 5.

To cite this abstract in AMA style:

Bosello S, De Lorenzis e, verardi l, Natalello g, Cerasuolo p, Di Donato S, Pellegrino G, De Luca G, Campochiaro C, Lepri G, Cometi L, Cacciapaglia F, Armetano G, De Pinto M, Motta F, De Santis M, Giuggioli D, Del Papa N, Iannone F, Guiducci S, Riccieri v, D'Agostino M, Del Galdo F. Mycophenolate Mofetil Use in Clinical Practice: Persistence on Therapy and Long-term Adverse Events in a Multicentric Cohort of Scleroderma Patients [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/mycophenolate-mofetil-use-in-clinical-practice-persistence-on-therapy-and-long-term-adverse-events-in-a-multicentric-cohort-of-scleroderma-patients/. Accessed .

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