The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related ...adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described.
In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (n = 3) or resorptive bone lesions (n = 3) that developed while on agents targeting PD-1, CTLA-4 or both. The average age of patients was 59.3 (SD 8.6), and five were male. Cancer types included melanoma, renal cell carcinoma and non-small cell lung cancer. All fracture patients had vertebral compression, and two of the three had multiple fracture sites involved. Sites of resorptive lesions included the shoulder, hand and clavicle. Biochemically, elevated or high-normal markers of bone resorption were seen in five of the six patients. Erythrocyte sedimentation rate was elevated in three of the four patients where checked.
This case series represents the first description of potential skeletal adverse effects related to immune checkpoint inhibitors. These findings are important for providers caring for patients who experience musculoskeletal symptoms and may merit additional evaluation.
Objective
To provide evidence‐based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).
Methods
This guideline follows American ...College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation.
Results
This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence.
Conclusion
Application of these recommendations should consider patients’ individual risk for vaccine‐preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision‐making with patients is encouraged in clinical settings.
Introduction
To understand factors leading to biologic switches and to develop a readily usable model with data collected in clinical care at preceding visits, with the overall aim to predict the ...probability of switching biologic at a subsequent clinic visit in patients with rheumatoid arthritis (RA).
Methods
Participants were adults with RA participating in the CorEvitas RA registry. The study matched patients who switched biologics or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) with control patients who had not switched biologics/tsDMARDs; the cohort was divided into a training and test set for prediction model development and validation. Using the training set, the best subset regression, lasso, and elastic net methods were used to determine the best potential models. Area under the ROC curve (AUC) was used for the final selection of the best model, and estimated coefficients of this model were applied to the test dataset to predict switching.
Results
A total of 5050 patients were included, of whom 3016 were in the training set and 2034 were in the test dataset. The average age was 59.6 years, the majority were female (3998, 79.2%), and the average duration of RA at the time of switch or control visit was 12.8 years. The final model included prior Clinical Disease Activity Index (CDAI) by category, prior patient pain measurement, change in CDAI from baseline, age group, and number of prior biologics, all of which were significantly associated with switching biologics. The AUC was 0.690 for this model with the training dataset. The model was then applied to the test data with similar performance; the AUC was 0.687.
Conclusion
We have developed a simple model to determine the probability of switching biologics for RA at the following clinic visit. This model could be used in practice to provide clinicians with more information about their patient’s trajectory and likelihood of switching to a new biologic.
Raynaud phenomenon (RP) and associated digital ischemia can be among the most vexing clinical problems for patients with systemic sclerosis (scleroderma). Understanding the treatment approach to RP ...and associated ischemia and how to prevent digital ulcers is important for clinicians caring for these patients. This article reviews the management of RP and digital ischemic ulcers. The magnitude of the problem and pathophysiology of RP are first discussed, with an emphasis on recent advances in understanding of the disease process. Options for the practical pharmacologic and nonpharmacologic interventions for RP and digital ischemic ulcers are detailed.
•This scoping review provides an up-to-date overview of published evidence regarding the frequency and severity of acute viral respiratory AEs related to antirheumatic disease ...therapies.•Glucocorticoid use was associated with a higher frequency of acute upper and lower respiratory viral events.•Mild viral respiratory infections occurred more frequently in several studies in which patients were treated with JAKi, most notably at higher doses.•TNFi and IL-17 inhibitors seemed to be associated with higher frequency of mild viral respiratory infections such as URTI and nasopharyngitis.•Our review identifies a knowledge gap for most antirheumatic medications and their acute respiratory viral complications; in the context of the COVID-19 pandemic, increased widespread respiratory viral PCR testing offers immediate research opportunities to clarify the safety of antirheumatic therapies in terms of viral respiratory complications.
COVID-19 is an acute respiratory viral infection that threatens people worldwide, including people with rheumatic disease, although it remains unclear to what extent various antirheumatic disease therapies increase susceptibility to complications of viral respiratory infections.
The present study undertakes a scoping review of available evidence regarding the frequency and severity of acute respiratory viral adverse events related to antirheumatic disease therapies.
Online databases were used to identify, since database inception, studies reporting primary data on acute respiratory viral infections in patients utilizing antirheumatic disease therapies. Independent reviewer pairs charted data from eligible studies using a standardized data abstraction tool.
A total of 180 studies were eligible for qualitative analysis. While acknowledging that the extant literature has a lack of specificity in reporting of acute viral infections or complications thereof, the data suggest that use of glucocorticoids, JAK inhibitors (especially high-dose), TNF inhibitors, and anti-IL-17 agents may be associated with an increased frequency of respiratory viral events. Available data suggest no increased frequency or risk of respiratory viral events with NSAIDs, hydroxychloroquine, sulfasalazine, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, or apremilast. One large cohort study demonstrated an association with leflunomide use and increased risk of acute viral respiratory events compared to non-use.
This scoping review identified that some medication classes may confer increased risk of acute respiratory viral infections. However, definitive data are lacking and future studies should address this knowledge gap.
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.
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.
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.
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.
Within the context of the Competence Centre for the Conservation of Cultural Heritage (4CH) project, the design and deployment of a platform-as-a-service cloud infrastructure for the first European ...competence centre of cultural heritage (CH) has begun, and some web services have been integrated into the platform. The first integrated service is the INFN-CHNet web application for FAIR storage of scientific analysis on CH: THESPIAN-Mask. It is based on CIDOC-CRM-compatible ontology and CRMhs, describing the scientific metadata. To ease the process of metadata generation and data injection, another web service has been developed: THESPIAN-NER. It is a tool based on a deep neural network for named entity recognition (NER), enabling users to upload their Italian-written report files and obtain labelled entities. Those entities are used as keywords either to serve as (semi)automatically custom queries for the database, or to fill (part of) the metadata form as a descriptor for the file to be uploaded. The services have been made freely available in the 4CH PaaS cloud platform.
The majority of patients with ICI-induced IA, more than 90% in one systematic review ( 3), are seronegative for classic rheumatoid arthritis (RA)–associated autoantibodies (ie, anti-cyclic ...citrullinated peptide anti-CCP antibodies) at the time of arthritis presentation. Clinical data, including cancer history and treatment, clinically obtained laboratory studies, and disease activity measures, were collected as part of this ongoing study. The two patients to test positive for anti-CCP antibodies were both treated with pembrolizumab but had different tumor types (pancreatic cancer and squamous cell carcinoma) and were different sexes, and one has survived long-term whereas the other is deceased.
Patients treated for cancer with immune checkpoint inhibitors (ICI) may develop autoimmune adverse events, including ICI-induced inflammatory arthritis (IA). ICI-induced IA treatment requires ...balancing immune activation to fight cancer and immune modulation to control autoimmunity. Our objective was to learn how patients experience ICI-induced IA and potentially conflicting treatment decisions.
Semi-structured interviews were conducted with participants with rheumatologist-diagnosed ICI-induced IA recruited from a longitudinal cohort. The interview guide probed the experience of diagnosis and treatment, symptoms and impact of ICI-induced IA, coping mechanisms, and treatment decision-making. Two researchers used an iterative coding process to identify themes through inductive thematic analysis and consensus. An overarching conceptual framework was derived from the qualitative analysis to identify care gaps perceived by patients, and inform future research.
Fourteen patients with ICI-induced IA participated in semi-structured interviews. Five overarching themes were identified: an awareness gap leading to delay in diagnosis of IA, descriptors of ICI-induced IA and relationship to other adverse events, emotional and quality-of-life impact of IA, fear and decision-making, and contextual factors including social support.
As reported by patients, ICI-induced IA had a significant functional and emotional impact, even as compared to cancer and other ICI-induced side effects. Increasing awareness and integrated care of ICI-induced IA, and increasing social support are key targets for improving patient care. Additionally, more data on cancer outcomes in patients requiring immunomodulation for ICI-induced IA would help address fear and uncertainty for patients, and better support them through therapeutic decisions.
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