Full Papers
Clinical outcomes in cancer patients with immune checkpoint inhibitor-induced arthritis treated with methotrexate: a retrospective longitudinal monocentric pilot study
E. Hysa1, A. Casabella2, N. Iandolino3, E. Gotelli4, C. Genova5, E.T. Tanda6, C. Pizzorni7, V. Smith8, A. Sulli9, M. Cutolo10, S. Paolino11
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genova, and Department of Experimental Medicine (DIMES), University of Genova, Italy.
- IRCCS Ospedale Policlinico San Martino, Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genova, and IRCCS Ospedale Policlinico San Martino, Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genova, Italy.
- Medical Oncology Clinic, IRCCS Ospedale Policlinico San Martino, Genova, and Department of Internal Medicine and Medical Specialties, University of Genova, Italy.
- Department of Internal Medicine and Medical Specialties, University of Genova, and Medical Oncology Clinic 2, Department of Internal Medicine, University of Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genova, and IRCCS Ospedale Policlinico San Martino, Genova, Italy.
- Department of Internal Medicine, Ghent University, and Department of Rheumatology, Ghent University Hospital; and Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genova, and IRCCS Ospedale Policlinico San Martino, Genova, Italy.
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genova, and IRCCS Ospedale Policlinico San Martino, Genova, Italy. mcutolo@unige.it
- Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Genova, and IRCCS Ospedale Policlinico San Martino, Genova, Italy.
CER18297
2025 Vol.43, N°5
PI 0867, PF 0873
Full Papers
Free to view
(click on article PDF icon to read the article)
PMID: 39907616 [PubMed]
Received: 01/11/2024
Accepted : 15/01/2025
In Press: 24/01/2025
Published: 08/05/2025
Abstract
OBJECTIVES:
Immune-mediated adverse events (irAEs) from immune checkpoint inhibitors (ICIs) often require high-dose glucocorticoids (GCs), which can promote cancer progression and counteract ICI benefits. This study evaluated the articular and oncologic clinical outcomes of ICI-induced arthritis treated with methotrexate (MTX) as a GC-sparing agent.
METHODS:
Adult patients with ICI-induced arthritis in 2023 were included. Arthritis was assessed using the disease activity score on 28 joints by C-reactive protein (DAS28-CRP), with follow-ups every 3 months. All patients received subcutaneous MTX, and oncologic outcomes were evaluated using RECIST 1.1 criteria after one year.
RESULTS:
Fourteen patients (median age 74.5 years) with melanoma (64.3%), colorectal cancer (14.3%), lung cancer (14.3%), or Hodgkin’s lymphoma (7.1%) were treated with PD1 antagonists (92.9%) or combined with CTLA4 blockers (7.1%). Arthritis presentations included oligo-arthritis (36%), mono-arthritis (29%), polyarthritis (21%), and polymyalgia rheumatica-like syndrome (14.3%), with a mean onset of 4.7±3.7 months post-ICI. MTX was started for all at a mean dose of 9.5±1.5 mg weekly, beginning at the first rheumatology visit in 78.5% of patients. Over a mean follow-up of 12.8±4.6 months, DAS28-CRP scores improved significantly, and prednisone dosage was in all reduced (3.6 mg at V4 vs. 8.4 mg at V0, p=0.003). No major MTX-related toxicities were noted. Cancer responses at follow-up were complete (50%), partial (21.4%), stable disease (7.1%), and progression (21.5%).
CONCLUSIONS:
The use of MTX in ICI-induced arthritis showed promising results in reducing GC dosages and managing the inflammatory articular activity, with no major toxicities observed over one year. These findings suggest that MTX may be a viable GC-sparing option in this context, but larger, controlled studies are needed to confirm these observations and better understand the impact on both articular and oncologic outcomes.
