bDMARDs Superior to MTX in Rapid Disease Control in ICI-Associated Inflammatory Arthritis

In patients with severe ICI-associated inflammatory arthritis, bDMARDs may be considered over methotrexate in achieving rapid disease control.

Compared with methotrexate (MTX), biologic disease modifying antirheumatic drugs (DMARDs) may rapidly control immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA); however, bDMARDs vs MTX are associated with a shorter time to cancer progression, according to research results published in Annals of the Rheumatic Diseases.

Literature has shown that ICI-IA affects up to 4% of cancer-treated patients. Although low-grade ICI-IA is typically managed with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose prednisone, a higher-grade arthritis is typically treated with DMARDs. However, second-line immunosuppression may potentially lead to immune-related adverse events and worse cancer outcomes.

Because limited data are available comparing the safety and efficacy of DMARDs vs MTX, researchers studied the association between these treatments with regard to cancer progression in ICI-IA.

A retrospective, multicenter observational study was conducted, using prospective clinical data collected from Johns Hopkins University and Hospital for Special Surgery, and retrospective data from electronic medical records at 4 sites in the US.

Arthritis control was more rapid in patients treated with biologic DMARDs, particularly TNFi, compared with MTX.

Inclusion criteria were diagnosis of ICI-IA or ICI-associated polymyalgia rheumatica and treatment with DMARDs (tumor necrosis factor inhibitor (TNFi) and interleukin [IL]-6 receptor inhibitor and/or methotrexate).

Primary study outcome was ICI initiation to cancer progression; secondary outcome was time from DMARD initiation to arthritis control, defined by the Common Terminology Criteria for Adverse Events.

A total of 147 patients (mean age, 60.3 years; 55% men) with cancer and ICI-IA were included in the study, of whom 22% (n=33) received TNFis, 29% (n=42) received IL-6 receptor inhibitors (n=42), and 49% (n=72) received MTX.

Researchers found earlier cancer progression in patients receiving treatment with TNFis (hazard ratio [HR], 2.51; 95% CI, 0.91-6.93; P =.075) or IL-6 receptor inhibitors (HR, 2.36; 95% CI, 0.91-6.12; P =.078).

Based on the adjusted model for time from ICI initiation to DMARD initiation, the HR for TNFis vs MTX was significant (HR, 3.27; 95% CI, 1.21-8.84; P =.019). No significant time difference in progression to cancer was observed in those receiving TNFis vs IL-6 receptor inhibitors (HR, 1.38; 95% CI, 0.58-3.3; P =.47).

After adjusting for age, ICI type, cancer type and stage, a faster ICI-IA control from DMARD initiation was observed among patients who received TNFis (HR, 1.91; 95% CI, 1.06-3.45; P =.032) and IL-6 receptor inhibitors (HR, 1.66; 95% CI,0.93-2.97; P =.089). 

The ICI-IA control was most significant in the first 90 days. Researchers showed that TNFis and IL-6 receptor inhibitors (HRs, 3.05 [95% CI, 1.37-6.76]; P =.006 and 2.16 [95% CI, 0.98-4.74]; P =.055, respectively) were more rapid in disease control compared with MTX.

Study limitations included differences in the duration of DMARD use between treatment groups, as well as variability in cancer types.

The study authors stated, “We demonstrate faster cancer progression with biologic DMARDs compared with MTX, which was significant for TNFi after adjustment for the time from ICI initiation to DMARD start. Arthritis control was more rapid in patients treated with biologic DMARDs, particularly TNFi, compared with MTX.”

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Bass AR, Abdel-Wahab N, Reid PD, et al. Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritisAnn Rheum Dis. Published online April 5, 2023. doi:10.1136/ard-2023-223885