Systemic treatment of immune checkpoint inhibitor-induced psoriasis: Inference-based guidance

Abstract

Background: Immune checkpoint inhibitors (ICIs) are increasingly used to treat various cancers. Their use may result in immune-related adverse events, including psoriasis. When managing psoriasis, induced or exacerbated by an ICI, there are concerns regarding immunosuppression from systemic agents for the treatment of psoriasis (saPs) and the potential impact on ICI efficacy. No direct, high-level evidence exists to address these concerns.

Objective: To address clinically relevant questions regarding the management of ICI-mediated psoriasis (ICI-Ps) with saPs.

Methods: We convened a multidisciplinary panel of 15 international specialists in dermatology, oncology, immunology, and rheumatology. A Delphi process defined clinical concerns related to the systemic treatment of ICI-Ps, focusing on the potential of saPs to impact ICI effectiveness. The saPs considered included biologics targeting tumour necrosis factor, interleukin (IL)-17, IL-12/23 and IL-23, traditional systemic therapies (cyclosporine, methotrexate), small molecules targeting phosphodiesterase-4 or tyrosine kinase 2, systemic retinoids (acitretin), and systemic corticosteroids. A systematic review of the literature was supplemented with evidence supporting an inference-based methodology to derive conclusions on the use of systemic therapies in patients with ICI-Ps. The specialist panel rated the strength of the conclusions using a probabilistic scale.

Results: After reviewing the totality of direct and indirect evidence, we drafted inference-based conclusions and ascribed a level of support, focusing on the potential impact of saPs on ICI efficacy. This work provides a structured framework informing healthcare professional and patient discussions on the risks and benefits of using saPs in patients with cancer who experience ICI-Ps.

Conclusions: Although there is no direct evidence, we support the following conclusions: saPs may be used to treat ICI-Ps without an appreciable loss of ICI effectiveness. Generally, it is not necessary to interrupt ICI therapy. When available, non-steroid saPs are preferred over systemic corticosteroids for the treatment of psoriasis.

Keywords: atezolizumab; avelumab; cemiplimab; dostarlimab; durvalumab; guideline; immune checkpoint inhibitors; immune‐related adverse events; immunomodulating agents; immunosuppressive agents; ipilimumab; nivolumab; pembrolizumab; psoriasis.

FIGURE 1

Decision framework for treating ICI‐Ps with systemic therapies. This decision framework intends to assist in clinical decision‐making. Statements are not meant to be hierarchical or proscriptive. The statements are intended as advisements with levels of support and estimates of confidence reflecting expert belief based on the best available data. For details, refer to the text of this manuscript. Although systemic corticosteroids are often used by oncologists for the treatment of ICI‐Ps, use of high‐dose systemic corticosteroids should be minimized and low‐dose systemic corticosteroids are not preferred for long‐term use. ^aTraditional systemic agents including cyclosporine, methotrexate and retinoids are slow to act and less well tolerated than newer small molecules and biologic agents. The group did not agree on a statement for the use of cyclosporine A in ICI‐Ps. ^bBiologic agents have a higher efficacy, faster onset of action (2–11 weeks), target specificity and may improve ICI efficacy as per pre‐clinical studies. They are not widely used in cancer patients, and there is minimal direct evidence to support their use. ^cCaution for exacerbation of new onset inflammatory bowel disease and colitis. ^dCaution for tuberculosis reactivation. CI, confidence interval; ICI, immune checkpoint inhibitor; ICI‐Ps, ICI‐mediated psoriasis; IL, interleukin; PDE‐4, phosphodiesterase‐4; saPs, systemic agents for the treatment of psoriasis; TNF, tumour necrosis factor; TYK2, tyrosine kinase 2.