IL-17/IL-23 Targeting Safely Managed PsA in 3 Patients With Cancer on Immune Checkpoint Inhibitor Therapy

Targeting the IL-17/23 axis was effective and safe in 3 patients with cancer and pre-existing psoriatic arthritis (PsA) being considered for immune checkpoint inhibitor (ICI) therapy.¹

“Although ICIs are revolutionizing cancer treatment, they are also associated with life-/organ-threatening adverse events including de novo irAEs and flare of pre-existing ADs. It has been observed that up to 80% of psoriasis (PsO)/PsA patients with cancer experience flare of their pre-existing PsO/PsA after ICI therapy,” lead investigator Yuanteng Jeff Li, MD, RhMSUS, FACR, Assistant Professor, Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, and colleagues wrote.¹

Li and colleagues reported data from 3 patients with PsA and cancer who received ICIs as cancer treatment. All were male, with 2 of clear cell renal cell carcinoma (ccRCC)and 1 case of melanoma. Two patients received anti-PD-1 antibody monotherapy and 1 patient received combined anti-CTLA-4 and PD-1 antibody therapy. One patient had been receiving anti-IL-17A antibody (secukinumab) and the other 2 patients started anti-IL-17A antibody (ixekizumab) and anti-IL-23 antibody (guselkumab) after their PsA flared up during ICI treatment. Overalll, anti-IL-17A or anti-IL-23 antibody treatments managed PsA and kept it in remission while patients tolerated ICI therapy well. Notably, ICI therapy yielded persistent tumor responses in all 3 patients, with 2 complete responses and 1 case of stable disease.¹

Specifically, the first patient was a 72-year-old male with a history of PsA, osteoarthritis (OA), and metastatic melanoma, who was initially treated with methotrexate, etanercept, and ultraviolet therapy for PsA, and Mohs surgery for melanoma. After melanoma recurred and was treated with surgery and radiation, secukinumab was introduced to manage PsA. Despite mild PsA flares controlled by secukinumab, the patient experienced neuritis and PsA flares during pembrolizumab treatment for new esophageal lesions. Secukinumab was paused for knee replacements and then resumed, with prednisone used temporarily. After completing all treatments, including proton therapy for melanoma, PsA was well-controlled and melanoma was in remission at the last rheumatology visit, 32 months after starting pembrolizumab.¹

The second patient was a 47-year-old man with PsA and ccRCC initially treated with adalimumab for PsA, which was effective until he developed ccRCC, leading to the discontinuation of adalimumab and treatment with partial nephrectomy. Following brain metastases and radiation therapy, his ccRCC progressed despite tyrosine kinase inhibitors. Before starting pembrolizumab and axitinib, he was asymptomatic for PsA. After beginning treatment, he experienced PsA and psoriasis flares, managed with ixekizumab and a short course of prednisone while continuing pembrolizumab and axitinib. Despite new brain metastases, his extracranial ccRCC remained well-controlled, and at the latest follow-up, his PsA was well-managed with ixekizumab, and his ccRCC was stable with no recurrent brain metastases.¹

The last patient was a 60-year-old man with PsA, metastatic ccRCC, and a history of melanoma in remission, who was initially treated with sulfasalazine for PsA. After undergoing partial nephrectomy for ccRCC and experiencing recurrent cancer, he began combined ipilimumab and nivolumab therapy. Despite being asymptomatic at his rheumatology visit, he developed transaminitis and thyroiditis from the treatment, leading to a temporary halt of tocilizumab. Following its resumption, he experienced a PsA flare, prompting the discontinuation of tocilizumab and the introduction of guselkumab, an anti-IL-23 antibody. Guselkumab effectively controlled his PsA, allowing him to taper off prednisone while continuing ICI therapy. At his latest visit, his PsA remained well-managed with guselkumab, and his ccRCC was in remission.¹

“As ICIs increasingly become therapeutic mainstays for multiple malignancies, clinicians will encounter challenging cases, including managing PsO/PsA during ICI therapy. Our case series suggests that targeting the IL-23/IL-17 axis could be a promising therapeutic strategy in this setting.² However, with a small number of cases and the controversial role of the IL-23/IL-17 axis in cancer, we cannot make definitive conclusions at this moment. Future studies with larger numbers of patients, standardized measurement of PsO/PsA and concurrent analyses of the patients’ samples are warranted,” Li and colleagues concluded.¹

REFERENCES

1. Li YJ, Msaouel P, Campbell M, Hwu P, Diab A, Kim ST. Successful management of pre-existing psoriatic arthritis through targeting the IL-23/IL-17 axis in cancer patients receiving immune checkpoint inhibitor therapy: a case series. RMD Open 2024;10:e004308. doi: 10.1136/rmdopen-2024-004308

2. Abdel-Wahab N, Shah M, Lopez-Olivo MA, et al. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease. Ann Intern Med 2018;168:121. doi:10.7326/M17-2073