Biologic DMARDs control ICI-associated inflammatory arthritis quicker than methotrexate
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Key takeaways:
- Patients treated with tumor necrosis factor inhibitors experienced a shorter time until cancer progression.
- Patients who received methotrexate achieved control of their arthritis more rapidly.
Patients with immune checkpoint inhibitor-associated inflammatory arthritis who receive a biologic DMARD demonstrate quicker arthritis control, but also experience faster cancer progression, vs. methotrexate, according to data.
“In patients with moderate-to-severe [immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA)], methotrexate (MTX) is often used as a steroid-sparing agent either alone or in combination with a biologic DMARD,” Anne R. Bass, MD, of the Hospital for Special Surgery, and colleagues wrote in the Annals of the Rheumatic Diseases. “However, there are no studies comparing the relative safety of different DMARDs.”
To investigate the differences between various drug classes in patients with ICI-IA, Bass and colleagues conducted a retrospective observational study. To be included, patients were required to have a diagnosis of ICI-IA with joint swelling or ICI-associated polymyalgia rheumatica with one or more inflamed peripheral joints. Also, these patients needed to be receiving treatment with a TNF inhibitor, an interleukin (IL)-6 receptor inhibitor, or methotrexate. Patients were excluded from the analysis if they presented with a preexisting autoimmune disease.
The primary outcome was the time from ICI initiation until cancer progression, as defined by the treating oncologist. Second to this was overall survival. Secondary outcomes included the time from DMARD initiation until the arthritis could be defined as controlled. In cases where arthritis grade was not recorded or available for analysis, Bass and colleagues used the Clinical Disease Activity Index scores. If neither score was available, they interpreted notes from patient files to determine severity and disease control.
The analysis included 147 patients. Of those, 33 received TNF inhibitors, 42 received IL-6 inhibitors and 72 received methotrexate. In all cases, the researchers adjusted for the time between ICI initiation and DMARD initiation. Following adjustment, the time to cancer progression was significantly shorter in patients who received TNF inhibitors compared with those who received methotrexate (HR = 3.27; 95% CI, 1.21-8.84).
For patients receiving the IL-6 receptor inhibitor, the hazard ratio was 2.37 (95% CI, 0.94-5.98). In addition, patients who received TNF inhibitors achieved arthritis control more quickly than patients who received methotrexate (HR = 1.91; 95% CI, 1.06-3.45).
“This is the first study to compare the association between the use of biologic and conventional synthetic DMARDs and cancer progression and arthritis control in patients with ICI-IA,” Bass and colleagues wrote. “We demonstrate faster cancer progression with biologic DMARDs compared with MTX, which was significant for [TNF inhibitors] after adjustment for the time from ICI initiation to DMARD start.”
Editor's note: On June 26, 2023, this story was updated to more accurately reflect the nature of the relationship between TNF inhibitors and cancer progression. Healio editors regret the error.
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Low grade immune-related adverse events (irAEs) can often be treated with low-dose prednisone, hydroxychloroquine, NSAIDs, and/or intra-articular corticosteroids. More severe cases require moderate-to-high doses of prednisone, methotrexate, and even biologic DMARDs. However, the concern is treating the irAEs without interfering with the cancer treatment and worsening the cancer outcome. Prior publications showed progression free survival was shorter in patients receiving immunosuppression at immune checkpoint inhibitors (ICI) initiation.
The present study demonstrated faster cancer progression with biologic DMARDs compared with methotrexate, as has been shown in other studies. The researchers noted that methotrexate appeared to be the optimal approach for those patients with persistent ICI-associated arthritis (ICI- IA) managed on prednisone 15 mg per day or less. However, for those with high-grade ICI-IA and requiring high-dose steroids for self-care, biologic DMARDs were faster acting and could allow a more rapid taper from high-dose steroids to avoid toxicity.
Hopefully, a future prospective study will help answer the question of optimal management for persistent, high-grade ICI-IA in patients with cancer.
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