Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy, increasingly utilized to treat malignancies. Inflammatory arthritis (IA) is a potential consequence of ICI use, but there is ...limited information to guide evaluation and management of this immune-related adverse event (irAE). This study aimed to characterize clinical phenotypes, IA treatment and response in the largest cohort of patients with ICI-induced IA reported to date.
Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of autoimmune disease were included. Data were analyzed by ICI treatment regimen; treatments included combination CTLA-4/PD-1 inhibition, anti-PD-1 or anti-PD-L1 monotherapy. Relationship to the development of other irAEs, management of IA, and outcomes of IA management were evaluated.
Of 30 patients identified, those treated with combination ICI therapy were more likely to present with knee arthritis, to have higher levels of C-reactive protein, to have already had another irAE, and to have a reactive arthritis-like phenotype. In contrast, patients treated with ICI monotherapy were more likely to have initial small joint involvement and to have IA as their only irAE. Ten patients required additional immunosuppression beyond corticosteroids, with TNF-inhibitors and/or methotrexate. Tumor progression while on non-corticosteroid immunosuppression was not seen in those with initial tumor response to ICIs.
These data suggest that distinct IA phenotypes may emerge with exposure to different ICI regimens. The majority of patients referred to rheumatology required systemic immunosuppression to manage their IA symptoms. Tumor progression was not seen in patients requiring TNF-inhibitors.
Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
The relationships between cancer and autoimmune rheumatic diseases Cappelli, Laura C.; Shah, Ami A.
Baillière's best practice and research in clinical rheumatology/Baillière's best practice & research. Clinical rheumatology,
February 2020, 2020-02-00, 20200201, Letnik:
34, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Links between autoimmune rheumatic diseases and cancer continue to be elucidated. In this review, we explore this complex, bidirectional relationship. First, the increased risk of cancer across the ...breadth of the autoimmune rheumatic diseases is described. The magnitude of risk and types of tumors seen can differ by the type of autoimmune disease, timing of disease course, and even clinical and laboratory features within a particular autoimmune disease, suggesting that targeted cancer screening strategies can be considered. Multiple mechanisms linking autoimmune rheumatic diseases and cancer are discussed, including the development of autoimmunity in the context of naturally occurring anti-tumor immune responses and malignancy arising in the context of inflammation and damage from autoimmunity. Immunosuppression for rheumatic disease can increase risk for certain types of cancers. Finally, immune checkpoint inhibitors, a type of cancer immunotherapy, which cause a variety of inflammatory syndromes of importance to rheumatologists, are reviewed.
Immune checkpoint inhibitors (ICIs) have now been approved in numerous and diverse cancer types and combination regimens. Effective recognition and treatment of ICI toxicities, which might occur ...acutely, affect any organ system, and produce many distinct clinical syndromes, have emerged as essential goals of ICI management. Thus, developing robust diagnostic and management approaches for ICI toxicity across the health-care system is an urgent and unmet clinical need. In this Personal View, we describe barriers to high-quality care that have constrained the most effective management of patients with cancer receiving ICI treatment. We review education initiatives to enhance patient and physician awareness, which is necessary given the broad spectrum of ICI toxicities often experienced by patients, and assess various systems-based approaches that maximise the chances of appropriate management. In addition, we describe research pipelines that broaden evidence-based approaches and the pathobiology of these novel events. Developing effective, systematic approaches for the recognition and treatment of ICI toxicities will continue to grow in importance as these agents proliferate in cancer care.
To determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA).
Participants ...were adults with rheumatologist diagnosed ICI-IA. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of IA > 6 months after ICI cessation and requirement of corticosteroids. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate.
126 patients with ICI-IA were included; 53 patients (42%) required a csDMARD/bDMARD. In univariate logistic regressions, higher CDAI, tenosynovitis, longer symptom duration before first rheumatology visit, and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; there was a trend toward those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration, and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4/PD-1 therapy and steroid use at baseline were associated with a higher risk of persistent IA.
Higher levels of disease activity, tenosynovitis, and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI-IA, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial steroid dose, earlier rheumatology referral, and adoption of immunosuppression beyond steroids to improve outcomes.
The introduction of immune checkpoint inhibitors (ICIs) has changed the landscape of the treatment of cancer. Several immune-related adverse events (irAEs) have now been described such as ...ICI-inflammatory arthritis (IA), sicca syndrome, polymyalgia rheumatica, myositis, and vasculitis as a consequence of immune activation. The onset of the ICI-IA can vary from after the first infusion of ICIs to a delayed presentation a year or more after ICI initiation. Ultimately, baseline patient and tumor characteristics, the types of immunotherapies used, pre-existing autoimmune diseases, and/or other irAEs, as well as patient preferences will all shape the discussions around ICI-IA management.
The development of inflammatory arthritis in patients receiving immune checkpoint inhibitor therapy is increasingly recognized due to the growing use of these drugs for the treatment of cancer. This ...represents an important opportunity not only to define the mechanisms responsible for the development of this immune‐related adverse event and to ultimately predict or prevent its development, but also to provide a unique window into early events in the development of inflammatory arthritis. Knowledge gained through the study of this patient population, for which the inciting event is known, could shed light into the pathogenesis of autoimmune arthritis. This review will highlight the clinical and immunologic features of these entities to define common elements for future study.
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