Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis

Abstract

ObjectivesTo compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA).MethodsThe retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders.Results147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control.ConclusionThe treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.

Inhibiting the Inhibitor in Synovial Macrophages and Cancer Immunotherapy–Associated Inflammatory Arthritis

“…12,13 However, besides the potential sideeffects, there is concern that at least some immunosuppressants could reduce the time to cancer recurrence. 14,15 This study highlights the potential role of PD-L1 + synovial macrophages and lends important preliminary support to further correlational studies in humans and mechanistic studies in mouse models to validate their findings. Although generalized depletion of myeloid cells by clodronate liposome treatment during disease induction in mouse models of autoimmune arthritis prevents arthritis, this approach also leads to the loss of subsets of macrophages that play an anti-inflammatory role.…”

“…Disease‐modifying antirheumatic drugs such as methotrexate, tumor necrosis factor and interleukin 6R inhibitors can also be used 12,13 . However, besides the potential side‐effects, there is concern that at least some immunosuppressants could reduce the time to cancer recurrence 14,15 . This study highlights the potential role of PD‐L1 + synovial macrophages and lends important preliminary support to further correlational studies in humans and mechanistic studies in mouse models to validate their findings.…”

Significantly Delayed Development of Polyarthritis with Active Tenosynovitis after Possible Temporary Neutropenic Immune-Related Adverse Events Caused by Atezolizumab Treatment: A Novel Case Report

“…In contrast, combination immunosuppressive treatment for irAE management (steroids with other medications) resulted in poor ICI treatment efficacy compared to prednisolone monotherapy in ipilimumab and nivolumab treatment for melanoma [ 12 ]. In addition, Bass et al have shown that TNF α inhibitor use for Rh-irAE treatment shortened the time to cancer progression compared to methotrexate [ 13 ]. Mitchell et al have also reported the possibility of decreased ICI efficacy by prolonged immunomodulation in patients receiving anti-programmed death-1 antibodies [ 5 ].…”

Rheumatic complications of checkpoint inhibitors: Lessons from autoimmunity

“… 107 In agreement with this there is evidence that treatment of irAE‐arthritis with biologic therapies, particularly anti‐TNF therapy, shortens the time to cancer progression, presumably preventing development of robust and persistent memory. 108 …”