Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series
Abstract
Background Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects.Case reports The anti-interleukin (IL)-6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition.Conclusions These three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs.
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IL-6 inhibition may rebalance the altered Th17-Treg axis without inhibiting the Th1-CD8+ T-cell subsets that are required for antitumor immunity.
“Consequently, IL-6 inhibition may rebalance the altered Th17-Treg axis without inhibiting the Th1-CD8þ T-cell subsets that are required for antitumor immunity.58”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [58]
A study reported that tocilizumab was used successfully to treat ICI-related arthritis.
“Additionally, a study reported that TCZ was used successfully to treat ICI-related arthritis.58”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [58]
Cites
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157 · see citing works
IL‐6 in inflammation, immunity, and disease
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016295 · Cited by 5,046 · see citing works
Couzin-Frankel, J. (2013) · Science · doi:10.1126/science.342.6165.1432 · Cited by 2,051 · see citing works
IL‐6: Regulator of Treg/Th17 balance
Kimura, A., & Kishimoto, T. (2010) · European Journal of Immunology · doi:10.1002/eji.201040391 · Cited by 1,605 · see citing works
Horvat, T. Z., Adel, N. G., Dang, T.-O., Momtaz, P., Postow, M. A., Callahan, M. K., Carvajal, R. D., Dickson, M. A., D'Angelo, S. P., Woo, K. M., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.60.8448 · Cited by 1,064 · see citing works
The two faces of IL-6 on Th1/Th2 differentiation
Diehl, S. A., & Rincón, M. (2002) · Molecular Immunology · doi:10.1016/s0161-5890(02)00210-9 · Cited by 873 · see citing works
Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors
Friedman, C. F., Proverbs-Singh, T. A., & Postow, M. A. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.1051 · Cited by 801 · see citing works
Abdel‐Wahab, N., Shah, M., & Suarez-Almazor, M. E. (2016) · PLoS ONE · doi:10.1371/journal.pone.0160221 · Cited by 442 · see citing works
Self-citationInflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab
Cappelli, L. C., Gutierrez, A. K., Baer, A. N., Albayda, J., Manno, R., Haque, U. J., Lipson, E. J., Bleich, K. B., Shah, A. A., Naidoo, J., et al. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-209595 · Cited by 397 · see citing works
Targeting Th17 cells in autoimmune diseases
Yang, J., Sundrud, M. S., Skepner, J. E., & Yamagata, T. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.07.006 · Cited by 348 · see citing works
TNF-α is critical for antitumor but not antiviral T cell immunity in mice
Calzascia, T., Pellegrini, M., Hall, H., Sabbagh, L., Ono, N., Elford, A. R., Mak, T. W., & Ohashi, P. S. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32567 · Cited by 229 · see citing works
Calabrese, C. M., Kirchner, E., Kontzias, A., Velcheti, V., & Calabrese, L. H. (2017) · RMD Open · doi:10.1136/rmdopen-2016-000412 · Cited by 200 · see citing works
Evaluation of serum IL-17 levels during ipilimumab therapy: Correlation with colitis.
Callahan, M. K., Yang, A., Tandon, S., Xu, Y., Subudhi, S. K., Roman, R., Heine, A. I., Pogoriler, E., Kuk, D., Panageas, K., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.2505 · Cited by 129 · see citing works
Chan, M. M. K., Kefford, R. F., Carlino, M. S., Clements, A., & Manolios, N. (2014) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000060 · Cited by 119 · see citing works
Tartour, É., Dorval, T., Mosseri, V., et al. (1994) · British Journal of Cancer · doi:10.1038/bjc.1994.175 · Cited by 119 · see citing works
The IL-6 feed-forward loop: A driver of tumorigenesis
Chang, Q., Daly, L., & Bromberg, J. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.01.007 · Cited by 99 · see citing works
Mouawad, R., Benhammouda, A., Rixe, O., et al. (1996) · PubMed · Cited by 70 · see citing works
Uemura, M. I., Trinh, V. A., Haymaker, C., Jackson, N. A., Kim, D. W., Allison, J. P., Sharma, P., Vence, L. M., Bernatchez, C., Hwu, P., et al. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0309-7 · Cited by 69 · see citing works
Self-citationT Cells as Sources and Targets of TNF: Implications for Immunity and Autoimmunity
Chatzidakis, I., & Mamalaki, C. (2010) · Current directions in autoimmunity · doi:10.1159/000289200 · Cited by 53 · see citing works
Managing Adverse Events With Immune Checkpoint Agents
Dadu, R., Zobniw, C., & Diab, A. (2016) · The Cancer Journal · doi:10.1097/ppo.0000000000000186 · Cited by 48 · see citing works
Self-citationInterleukin-6 gene ablation in a transgenic mouse model of malignant skin melanoma.
von Felbert, V., Córdoba, F., Weissenberger, J., Vallan, C., Kato, M., Nakashima, I., Braathen, L., & Weis, J. (2005) · American Journal of Pathology · doi:10.1016/s0002-9440(10)62304-8 · Cited by 43 · see citing works
Mouawad, R., Khayat, D., Merle, S., et al. (1999) · Melanoma Research · doi:10.1097/00008390-199904000-00011 · Cited by 19 · see citing works
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Sorted by citations
Brahmer, J. R., Lacchetti, C., Schneider, B. J., Atkins, M. B., Brassil, K. J., Caterino, J. M., Chau, I., Ernstoff, M. S., Gardner, J. M., Ginex, P., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6385 · Cited by 3,713 · see citing works
Self-citationTreatment Outcomes of Immune-Related Cutaneous Adverse Events
Phillips, G. S., Wu, J., Hellmann, M. D., Postow, M. A., Rizvi, N. A., Freites-Martinez, A., Chan, D., Dusza, S., Motzer, R. J., Rosenberg, J. E., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.18.02141 · Cited by 241 · see citing works
Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation
Braaten, T. J., Brahmer, J. R., Forde, P. M., Le, D., Lipson, E. J., Naidoo, J., Schollenberger, M., Zheng, L., Bingham, C. O., Shah, A. A., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-216109 · Cited by 230 · see citing works
Haanen, J., Ernstoff, M. S., Wang, Y., Menzies, A. M., Puzanov, I., Grivas, P., Larkin, J., Peters, S., Thompson, J. A., & Obeid, M. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.03.285 · Cited by 222 · see citing works
Successful use of adalimumab in immune checkpoint inhibitor-associated inflammatory arthritis
Oke, A. R., Wheater, M., Karydis, I., & Wallis, D. (2018) · Rheumatology Advances in Practice · doi:10.1093/rap/rky001 · Cited by 11 · see citing works
- Authors
- Kim, S. T., Tayar, J., Trinh, V. A., Suarez-Almazor, M., Garcia, S., Hwu, P., Johnson, D. H., Uemura, M., & Diab, A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Baylor College of Medicine (US)
- Corresponding author
- Diab, Adi
- ORCID
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 76
- Issue
- 12
- Pages
- 2061-2064
- ISSN
- 0003-4967 (ISSN-L)
- OpenAlex
- W2747028021
- Cited by
- 170
- References
- 22
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 16 · 2023: 12 · 2022: 23 · 2021: 23 · 2020: 32 · 2019: 31 · 2018: 18 · 2017: 1
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- tocilizumab, immune checkpoint inhibitors, immune-related adverse events, IL-6 receptor inhibition, anti-IL-6 receptor antibody, TNF-alpha inhibitors, corticosteroids, immunosuppression, cancer immunotherapy
- MeSH terms
- Aged, Arthritis, Female, Humans, Immunosuppressive Agents, Immunotherapy, Male, Middle Aged, Neoplasms, Tumor Necrosis Factor-alpha, Treatment Outcome, Antirheumatic Agents, Cell Cycle Checkpoints, Antibodies, Monoclonal, Humanized
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