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Hydroxychloroquine is a safe and effective steroid-sparing agent for immune checkpoint inhibitor–induced inflammatory arthritis

  • Janet RobertsEmail author
  • Michael Smylie
  • John Walker
  • Naveen S. Basappa
  • Quincy Chu
  • Michael Kolinsky
  • Christopher Lyddell
  • Carrie Ye
Brief Report
  • 52 Downloads

Abstract

Immunotherapy for cancer treatment continues to evolve, and immune checkpoints have proven successful therapeutic targets. With success has come the challenge of managing the commonly associated immune-related toxicities. Arthralgias and arthritis are a common immune-related adverse event (IrAE), well described in the literature (Pardoll Nat Rev Cancer 12:252–264, 2012; Diesendruck and Benhar Drug Resist Updat 30:39–47, 2017; Cappelli et al. Arthritis Care Res 69:1751–1763, 2017; Brahmer et al. J Clin Oncol 36:1714–1768, 2018; Smith and Bass (2017). The optimal management of immune checkpoint inhibitor (ICI)–induced arthritis remains unclear. We describe the first series using hydroxychloroquine as a first-line disease-modifying antirheumatic drug (DMARD) for patients without pre-existing autoimmune disease, who developed arthritis secondary to ICI’s. This was a single-center retrospective observational study reporting all patients evaluated by rheumatologists affiliated with the University of Alberta, a large tertiary health care center in Northern Alberta, Canada, deemed to have inflammatory arthritis (IA) following ICIs. We identified 11 patients, without pre-existing autoimmune disease, who developed IA following ICIs. Most patients presented with a symmetrical polyarthritis with both large and small joint involvement. All patients were treated according to the outlined treatment protocol with hydroxychloroquine as a first-line steroid-sparing agent: either as monotherapy or in combination with tapering doses of systemic corticosteroids (3) or intra-articular steroid injections (6). One patient required the addition of methotrexate to control symptoms and none required biologic therapy. There were no reported adverse effects from hydroxychloroquine. Inflammatory arthritis is an important complication of ICIs leading to significant impact on patient quality of life. In our experience, in patients without pre-existing autoimmune disease, hydroxychloroquine is an effective first-line therapy for IA secondary to ICI therapy.

Keywords

Autoimmune disease Hydroxychloroquine Immunotherapy Inflammation Neoplasms 

Notes

Compliance with ethical standards

Retrospective data were used, and patients were not contacted for this study. Thus, ethics approval was received but individual patient informed consent was not required for this study by our institution.

Disclosures

None.

References

  1. 1.
    Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264CrossRefGoogle Scholar
  2. 2.
    Diesendruck Y, Benhar I (2017) Novel immune check point inhibiting antibodies in cancer therapy – opportunities and challenges. Drug Resist Updat 30:39–47CrossRefGoogle Scholar
  3. 3.
    Cappelli LC, Gutierrez AK, Bingham CO 3rd, Shah AA (2017) Rheumatic and musculoskeletal immune-related adverse events due to immune checkpoint inhibitors: a systematic review of the literature. Arthritis Care Res 69:1751–1763CrossRefGoogle Scholar
  4. 4.
    Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA, in collaboration with the National Comprehensive Cancer Network (2018) Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol 36:1714–1768CrossRefGoogle Scholar
  5. 5.
    Smith MH, Bass AR (2017) Arthritis after cancer immunotherapy: symptom duration and treatment response. Arthritis Care Res.  https://doi.org/10.1002/acr.23467
  6. 6.
    Cappelli LC, Gutierrez AK, Baer AN, Albayda J, Manno RL, Haque U, Lipson EJ, Bleich KB, Shah AA, Naidoo J, Brahmer JR, le D, Bingham CO III (2017) Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis 76:43–50CrossRefGoogle Scholar
  7. 7.
    Kim ST, Tayar J, Trinh V, Suarez-Almazor M, Garcia S et al (2017) Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series. Ann Rheum Dis 76:2061–2064CrossRefGoogle Scholar
  8. 8.
    Puzanov I, Diab A, Abdallah K et al (2017) Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) toxicity management working group. J Immunother Cancer 5:95.  https://doi.org/10.1186/s40425-017-0300-z CrossRefGoogle Scholar
  9. 9.
    Calabrese C, Kirchner E, Kontzias K, Velcheti V, Calabrese LH (2017) Rheumatic immune-related adverse events of checkpoint therapy for cancer: case series of a new nosological entity. RMD Open 3:e000412.  https://doi.org/10.1136/rmdopen-2016-000412 CrossRefGoogle Scholar
  10. 10.
    Belkhir R, Burel SL, Dunogeant L, Marabelle A, Hollebecque A, Besse B, Leary A, Voisin AL, Pontoizeau C, Coutte L, Pertuiset E, Mouterde G, Fain O, Lambotte O, Mariette X (2017) Rheumatoid arthritis and polymyalgia rheumatic occuring after immune checkpoint inhibitor treatment. Ann Rheum Dis 76:1747–1750CrossRefGoogle Scholar
  11. 11.
    Kuznik A, Bencina M, Svajger U, Jeras M, Rozman B, Jerala R (2011) Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol 186:4794–4804.  https://doi.org/10.4049/jimmunol.1000702 CrossRefGoogle Scholar
  12. 12.
    Platone D, Koudriavtseva T (2018) Current and future use of chlorquine and hydroxycloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review. Clin Drug Investig 38:653–671CrossRefGoogle Scholar
  13. 13.
    Willis R, Seif AM, McGwin G Jr, Martinez-Martinez LA, González EB, Dang N, Papalardo E, Liu J, Vilá LM, Reveille JD, Alarcón GS, Pierangeli SS (2012) Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA, a multiethnic US cohort. Lupus 21(8):830–835.  https://doi.org/10.1177/0961203312437270 CrossRefGoogle Scholar
  14. 14.
    Suarez-Almazor ME, Belseck E, Shea B, Homik J, Wells G, Tugwell P (2000) Antimalarials for treating rheumatoid arthritis. Cochrane Database Syst Rev 2000(4):CD000959Google Scholar
  15. 15.
    Pascolo S (2016) Time to use a dose of chloroquine as an adjuvant to anti-cancer chemotherapies. Eur J Pharmacol 771:139–144CrossRefGoogle Scholar
  16. 16.
    Verbaanderd C, Maes H, Schaaf MB, Sukhatme VP, Pantziarka P, Sukhatme V et al (2017) Repurposing drugs in oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience 11:1–35CrossRefGoogle Scholar
  17. 17.
    Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, Jordan K, on behalf of the ESMO Guidelines Committee (2017) Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28(Suppl_4):iv119–iv142CrossRefGoogle Scholar
  18. 18.
    Horvat TZ, Adel NG, Dang TO, Momtaz P, Postow MA, Callahan MK et al (2015) Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol 33:3193–3198CrossRefGoogle Scholar
  19. 19.
    Kostine M, Rouxel L, Barnetche T, Veillon R, Martin F, Dutriaux C, Dousset L, Pham-Ledard A, Prey S, Beylot-Barry M, Daste A, Gross-Goupil M, Lallier J, Ravaud A, Forcade E, Bannwarth B, Truchetet ME, Richez C, Mehsen N, Schaeverbeke T, FHU ACRONIM (2018) Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer – clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis 77:393–398CrossRefGoogle Scholar
  20. 20.
    Esfahani K, Miller WH (2017) Reversal of autoimmune toxicity and loss of tumor response by interleukin-17 blockade. N Engl J Med 376:1989–1991CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of MedicineDalhousie UniversityHalifaxCanada
  2. 2.Division of Medical Oncology, Department of Oncology, Cross Cancer InstituteUniversity of AlbertaEdmontonCanada
  3. 3.Division of Rheumatology, Department of MedicineUniversity of AlbertaEdmontonCanada

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