DMARDs for treatment-related arthritis: MTX versus biologics

Innovative cancer drugs such as immune checkpoint inhibitors can have a significant impact in the fight against tumours, but they also have their downsides.

What is ICI-IA?

However, it is still unclear how these drugs influence the progression of the cancer. The problem is that highly immunosuppressive treatment of arthritis could counteract the antineoplastic effect of ICI.

How long does it take until cancer progression?

Rheumatologist Anne R. Bass and her team investigated the optimal treatment of patients with steroid-refractory or steroid-dependent ICI-IA in a retrospective, multicentre observational study. The study included 147 cancer patients with ICI-IA, 33 of whom were treated with TNFi, 42 with IL6Ri and 72 with MTX. The primary endpoint was the time to cancer progression from the start of ICI treatment. In addition, the time to arthritis control from the start of DMARD treatment was analysed. The median follow-up time was approximately 1,000 days.

The results show a clear trend

  1. The time to cancer progression was significantly shorter with biologic disease-modifying drugs (bDMARD) compared to MTX (TNFi: HR 3.27, 95% CI 1.21 to 8.84, p=0.019; IL6Ri: HR 2.37, 95% CI 0.94 to 5.98, p=0.055).
  2. However, the arthritis was brought under control more quickly with bDMARD than with MTX. This was achieved about twice as quickly with TNFi (HR 1.91, 95% CI 1.06 to 3.45, p=0.032) and a good 50 % faster with IL6Ri (HR 1.66, 95% CI 0.93 to 2.97, p=0.089).
  3. No significant difference in safety and efficacy was observed between TNFi and IL6Ri.

When MTX? When biologics?

The study authors conclude that MTX is preferable in patients with chronic, steroid-dependent ICI-IA if the activity of the arthritis allows it and the daily glucocorticoid dose does not exceed 15 mg prednisone. In severe ICI-IA, however, fast-acting bDMARDs such as TNFi and Il6Ri may need to be administered to control the arthritis and avoid high-dose steroid administration, but possibly at the cost of more rapid tumour progression.

Take-away for medical practice

In cancer patients who develop steroid-refractory arthritis during treatment with immune checkpoint inhibitors, very careful consideration must be made. Physicians should consider: How severe are the arthritis symptoms? How high is the required steroid dose? How stable is the underlying malignant disease? If DMARDs are used, MTX is preferable, while biologics are reserved for severe courses. Further studies should clarify whether TNF-a or IL-6 inhibitors should be taken into consideration.

  1. Bass AR et al. Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis. Ann Rheum Dis 2023; 82:920–926.