Hysa Elvis, Casabella Andrea, Iandolino Nicola, Gotelli Emanuele, Genova Carlo, Tanda Enrica Teresa, Pizzorni Carmen, Smith Vanessa, Sulli Alberto, Cutolo Maurizio, Paolino Sabrina
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.
Clin Exp Rheumatol. 2025 May;43(5):867-873. doi: 10.55563/clinexprheumatol/e49am5. Epub 2025 Jan 24.
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.
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.
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%).
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.
免疫检查点抑制剂（ICI）引发的免疫介导不良事件（irAE）通常需要大剂量糖皮质激素（GC）治疗，而这可能会促进癌症进展并抵消ICI的疗效。本研究评估了以甲氨蝶呤（MTX）作为GC节省剂治疗ICI诱导的关节炎的关节和肿瘤临床结局。
纳入2023年患有ICI诱导关节炎的成年患者。使用基于28个关节的疾病活动评分结合C反应蛋白（DAS28-CRP）评估关节炎情况，每3个月进行一次随访。所有患者均接受皮下注射MTX，并在一年后使用RECIST 1.1标准评估肿瘤学结局。
14例患者（中位年龄74.5岁），患有黑色素瘤（64.3%）、结直肠癌（14.3%）、肺癌（14.3%）或霍奇金淋巴瘤（7.1%），接受了PD1拮抗剂治疗（92.9%）或联合CTLA4阻滞剂治疗（7.1%）。关节炎表现包括少关节炎（36%）、单关节炎（29%）、多关节炎（21%）和风湿性多肌痛样综合征（14.3%），ICI治疗后平均发病时间为4.7±3.7个月。所有患者均开始使用MTX，平均剂量为每周9.5±1.5毫克，78.5%的患者在首次风湿科就诊时开始用药。在平均12.8±4.6个月的随访中，DAS28-CRP评分显著改善，泼尼松剂量均有所降低（V4时为3.6毫克，V0时为8.4毫克，p = 0.003）。未观察到与MTX相关的重大毒性反应。随访时癌症反应为完全缓解（50%）、部分缓解（21.4%）、疾病稳定（7.1%）和进展（21.5%）。
MTX用于治疗ICI诱导的关节炎在降低GC剂量和控制关节炎症活动方面显示出有前景的结果，一年内未观察到重大毒性反应。这些发现表明，在此背景下MTX可能是一种可行的GC节省选择，但需要更大规模的对照研究来证实这些观察结果，并更好地了解其对关节和肿瘤学结局的影响。
