Patient Experience of Systemic Sclerosis-Related Calcinosis: An International Study Informing Clinical Trials, Practice, and the Development of the Mawdsley Calcinosis Questionnaire.

Systemic sclerosis (SSc) -related calcinosis can be a debilitating, constantly painful, poorly understood vascular complication of calcium hydroxyapatite deposition in soft tissue structures that affects approximately 40% of both limited and diffuse cutaneous SSc subtypes. This publication describes the iterative and multitiered international qualitative investigations that yielded remarkable insights into natural history, daily experience, and complications of SSc-calcinosis providing pivotal information for health management. Patient-driven question development and field testing, according to Food and Drug Administration guidance, propelled the development of a patient-reported outcome measure for SSc-calcinosis, the Mawdsley Calcinosis Questionnaire.

Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group.

INTRODUCTION: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases may not be appropriate. We summarized clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set of outcome domains. METHODS: As the initial step of the core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provide both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter. RESULTS: We identified 69 publications, over a third of which utilized non-specific diagnoses of "arthritis," "arthralgia," and/or "PMR". Other publications provided the number, the distribution and/or names of specific joints affected, while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis. Most distinct domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 subsequent response, as well as 32 tumor response. CONCLUSION: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. There were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use.

Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology.

Immune checkpoint inhibition has resulted in significant efficacy across many cancer types, including melanoma. Melanoma is the second most common cancer among those of reproductive age, yet the reproductive toxicities of adjuvant and first-line immunotherapy are largely unknown.The normal innate and adaptive immune systems play a vital role in reproductive organ homeostasis of men and women and are essential for implantation, fertility, and a successful pregnancy. The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway is essential in several aspects of fertility and pregnancy. Recent studies have largely focused on the role of the PD-1/PD-L1 pathway in fetomaternal tolerance, highlighting the importance of intact immune regulation in promoting a successful pregnancy.In this review, we describe a case of a reproductive-aged female with stage IIIC melanoma who sought guidance on family planning after pembrolizumab therapy. We discuss the known fertility-related toxicities of immune checkpoint inhibitors, the potential targets for reproductive toxicity in males and nonpregnant females, and the implications of anti-PD-1 therapy in relation to fetomaternal tolerance. Informed decision making will benefit from data and consensus.

Checkpoint Inhibitors in Melanoma Patients with Underlying Autoimmune Disease.

The development of immune checkpoint inhibitors (ICI) has dramatically changed the clinical management of metastatic melanoma and other solid tumors. Despite exclusion from initial clinical trials, there is a growing body of retrospective data that suggest ICI can be used in patients with underlying autoimmune disease (AID) with a tolerable level of anticipated immune-related adverse events (irAEs) and a rate of severe irAEs comparable to that of patients without underlying AID. Coordination with other subspecialists and careful monitoring for irAEs is critical in safely managing these patients. Studies exploring novel approaches examining the use of targeted immunosuppressants in the prevention and management of irAEs, as well as multiple studies currently underway are aimed at establishing safe clinical practices when using ICI in patients with underlying AID.

Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors.

Immune checkpoint inhibitors are novel biologic agents to treat cancer by inhibiting the regulatory interactions that limit T cell cytotoxicity to tumours. Current agents target either CTLA-4 or the PD-1/PD-L1 axis. Because checkpoints may also regulate autoreactivity, immune checkpoint inhibitor therapy is complicated by side effects known as immune-related adverse events (irAEs). The aim of this article is to review the mechanisms of these events. irAEs can involve different tissues and include arthritis and other rheumatic manifestations. The frequency of irAEs is related to the checkpoint inhibited, with the combination of agents more toxic. Because of their severity, irAEs can limit therapy and require immunosuppressive treatment. The mechanisms leading to irAEs are likely similar to those promoting anti-tumour responses and involve expansion of the T cell repertoire; furthermore, immune checkpoint inhibitors can affect B cell responses and induce autoantibody production. Better understanding of the mechanisms of irAEs will be important to improve patient outcome as well as quality of life during treatment.