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

Anne R. Bass; Noha Abdel-Wahab; Pankti D. Reid; Jeffrey A. Sparks; Cassandra Calabrese; Deanna P. Jannat-Khah; Nilasha Ghosh; Divya Rajesh; Carlos Andres Aude; Lydia Gedmintas; Lindsey Macfarlane; Senada Arabelovic; Adewunmi Falohun; Komal Mushtaq; Farah Al Haj; Adi Diab; Ami A. Shah; Clifton O. Bingham; Karmela Kim Chan; Laura C. Cappelli

doi:10.1136/ard-2023-223885

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

Anne R. Bass, Noha Abdel-Wahab, Pankti D. Reid, Jeffrey A. Sparks, Cassandra Calabrese, Deanna P. Jannat-Khah, Nilasha Ghosh, Divya Rajesh, Carlos Andres Aude, Lydia Gedmintas, Lindsey Macfarlane, Senada Arabelovic, Adewunmi Falohun, Komal Mushtaq, Farah Al Haj, Adi Diab, Ami A. Shah, Clifton O. Bingham, Karmela Kim Chan, Laura C. Cappelli

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Objectives To compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA). Methods The 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. Results 147 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. Conclusion The 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.

Original language	English (US)
Pages (from-to)	920-926
Number of pages	7
Journal	Annals of the rheumatic diseases
Volume	82
Issue number	7
DOIs	https://doi.org/10.1136/ard-2023-223885
State	Published - Jul 1 2023
Externally published	Yes

Keywords

arthritis
biological therapy
methotrexate
outcome assessment, health care
tumor necrosis factor inhibitors

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy
Immunology
General Biochemistry, Genetics and Molecular Biology

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10.1136/ard-2023-223885

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Bass, A. R., Abdel-Wahab, N., Reid, P. D., Sparks, J. A., Calabrese, C., Jannat-Khah, D. P., Ghosh, N., Rajesh, D., Aude, C. A., Gedmintas, L., Macfarlane, L., Arabelovic, S., Falohun, A., Mushtaq, K., Haj, F. A., Diab, A., Shah, A. A., Bingham, C. O., Chan, K. K., & Cappelli, L. C. (2023). Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis. Annals of the rheumatic diseases, 82(7), 920-926. https://doi.org/10.1136/ard-2023-223885

Bass, AR, Abdel-Wahab, N, Reid, PD, Sparks, JA, Calabrese, C, Jannat-Khah, DP, Ghosh, N, Rajesh, D, Aude, CA, Gedmintas, L, Macfarlane, L, Arabelovic, S, Falohun, A, Mushtaq, K, Haj, FA, Diab, A, Shah, AA, Bingham, CO, Chan, KK & Cappelli, LC 2023, 'Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis', Annals of the rheumatic diseases, vol. 82, no. 7, pp. 920-926. https://doi.org/10.1136/ard-2023-223885

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

abstract = "Objectives To compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA). Methods The 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. Results 147 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. Conclusion The 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.",

keywords = "arthritis, biological therapy, methotrexate, outcome assessment, health care, tumor necrosis factor inhibitors",

author = "Bass, {Anne R.} and Noha Abdel-Wahab and Reid, {Pankti D.} and Sparks, {Jeffrey A.} and Cassandra Calabrese and Jannat-Khah, {Deanna P.} and Nilasha Ghosh and Divya Rajesh and Aude, {Carlos Andres} and Lydia Gedmintas and Lindsey Macfarlane and Senada Arabelovic and Adewunmi Falohun and Komal Mushtaq and Haj, {Farah Al} and Adi Diab and Shah, {Ami A.} and Bingham, {Clifton O.} and Chan, {Karmela Kim} and Cappelli, {Laura C.}",

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doi = "10.1136/ard-2023-223885",

language = "English (US)",

volume = "82",

pages = "920--926",

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publisher = "BMJ Publishing Group",

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TY - JOUR

T1 - Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis

AU - Bass, Anne R.

AU - Abdel-Wahab, Noha

AU - Reid, Pankti D.

AU - Sparks, Jeffrey A.

AU - Calabrese, Cassandra

AU - Jannat-Khah, Deanna P.

AU - Ghosh, Nilasha

AU - Rajesh, Divya

AU - Aude, Carlos Andres

AU - Gedmintas, Lydia

AU - Macfarlane, Lindsey

AU - Arabelovic, Senada

AU - Falohun, Adewunmi

AU - Mushtaq, Komal

AU - Haj, Farah Al

AU - Diab, Adi

AU - Shah, Ami A.

AU - Bingham, Clifton O.

AU - Chan, Karmela Kim

AU - Cappelli, Laura C.

PY - 2023/7/1

Y1 - 2023/7/1

N2 - Objectives To compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA). Methods The 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. Results 147 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. Conclusion The 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.

AB - Objectives To compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA). Methods The 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. Results 147 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. Conclusion The 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.

KW - arthritis

KW - biological therapy

KW - methotrexate

KW - outcome assessment, health care

KW - tumor necrosis factor inhibitors

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

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