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Immune checkpoint inhibitors (ICIs), used to treat many advanced cancers, activate the immune system to elicit an antitumor response. ICIs can also cause immune-related adverse events (irAEs) when nontumor tissues are affected by excess inflammation and autoimmunity. Rheumatic irAEs include inflammatory arthritis, myositis, sicca syndrome, polymyalgia rheumatica, and several other rare phenotypes. Treating rheumatic irAEs requires balancing the desire to decrease off-target inflammation while not negatively impacting the antitumor immune response. In this review, treatment recommendations for rheumatic irAEs have been discussed. Pathogenesis of rheumatic irAEs has been briefly reviewed. Knowledge about the effects of corticosteroids and steroid-sparing agents on tumor responses has been detailed to give context for treatment decisions. Recommendations ultimately depend not only on the clinical presentation and severity of the irAE but also on the goals of cancer treatment. Finally, how to safely use ICI therapy in patients with preexisting autoimmune diseases is considered.

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.

ObjectivesTo compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA).MethodsThe retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders.Results147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control.ConclusionThe treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines. Furthermore, there are no prospective trial data to inform the management of the distinct presentations of irAEs. Recognizing a need for uniform terminology for the natural history, response to treatment, and patterns of irAEs, the Society for Immunotherapy of Cancer (SITC) convened a consensus panel composed of leading international experts from academic medicine, industry, and regulatory agencies. Using a modified Delphi consensus process, the expert panel developed clinical definitions for irAE terminology used in the literature, encompassing terms related to irAE natural history (ie, re-emergent, chronic active, chronic inactive, delayed/late onset), response to treatment (ie, steroid unresponsive, steroid dependent), and patterns (ie, multisystem irAEs). SITC developed these definitions to support the adoption of a standardized vocabulary for irAEs, which will have implications for the uniform application of irAE clinical practice guidelines and to enable future irAE clinical trials.

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.

Highlights • 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., Introduction 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. Objective 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. Methods 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. Results 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. Conclusion 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 (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.

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.

Objective We performed a systematic literature review to identify all reports of immune checkpoint inhibitor-associated inflammatory arthritis to describe it phenotypically and serologically. Methods PubMed, Embase, and Cochrane databases were searched for reports of musculoskeletal immune-related adverse events secondary to ICI treatment. Publications were included if they provided individual patient level data regarding the pattern of joint involvement. Descriptive statistics were used to summarize results. Results A total of 4339 articles were screened, of which 67 were included, encompassing 372 patients. The majority of patients had metastatic melanoma (57%), and they were treated with anti-PD1 or anti-PDL1 therapy (78%). Median time to onset of arthritis was 4 months (range, 1 day to 53 months). Forty-nine percent had polyarthritis, 17% oligoarthritis, 3% monoarthritis, 10% arthralgia, and 21% polymyalgia rheumatica. More than half of patients were described as having a "rheumatoid arthritis-like" presentation. Nine percent tested positive for rheumatoid factor or anti-cyclic citrullinated peptide antibodies. Seventy-four percent required corticosteroids, and 45% required additional medications. Sixty-three percent achieved arthritis control, and 32% were ultimately able to discontinue antirheumatic treatments. Immune checkpoint inhibitors were continued in 49%, transiently withheld in 11%, and permanently discontinued due to musculoskeletal immune-related adverse events in 13%. Conclusions Half of reported immune checkpoint inhibitor-associated arthritis cases present with polyarthritis (often RA-like), but only 9% are seropositive. Polymyalgia rheumatica is also common. Most patients respond to steroids alone, but about half require additional medications. Further studies are needed to determine long-term musculoskeletal outcomes in these patients, and the impact of arthritis treatment on cancer survival.

ObjectivePatients with inflammatory arthritis (IA) associated with immune checkpoint inhibitor (ICI) treatment for cancer are typically seronegative for anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factor, but little is known about the presence of other autoantibodies in this patient population. We investigated the prevalence and characteristics of anti-RA33 antibodies in patients with ICI-induced IA.MethodsAnti-RA33 ELISAs were performed on sera from four groups of patients: 79 with ICI-induced IA, 52 with rheumatoid arthritis (RA), 35 treated with ICIs without IA during follow-up and 50 healthy controls. Anti-RA33 positivity and level, clinical and demographic data were compared across groups.ResultsAnti-RA33 antibodies were found in 9/79 (11.4%) patients with ICI-induced IA but in 0/35 patients treated with ICIs who did not develop IA (0%; p=0.04). Of the patients positive for anti-RA33, two had sera available from before ICI treatment; anti-RA33 antibodies were present in both pre-ICI treatments. In patients with RA, 7.7% were positive for anti-RA33 antibodies as were 2% of healthy controls. In ICI-induced IA, anti-RA33 antibodies were associated with anti-CCP antibodies (p=0.001). We found no statistically significant differences in other clinical characteristics in those with and without anti-RA33 antibodies.ConclusionsAnti-RA33 antibodies are present in a subset of patients with ICI-induced IA, absent in other ICI-treated patients and may be a biomarker for developing IA. Additional studies evaluating serial samples before and after ICI treatment will further establish the temporal relationship of these antibodies to IA development.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]

Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjogren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. Funding: American College of Rheumatology.

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide general guidance for commonly encountered clinical scenarios. The recommendations do not dictate the care for an individual patient. The ACR considers adherence to the recommendations described in this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinicians in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions, or drug formularies or other third-party analyses. Third parties that cite ACR guidelines should state that these recommendations are not meant for this purpose. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. 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.

Immune checkpoint inhibitors are a major breakthrough in the field of oncology. Targets for approved immune checkpoint inhibitors are cytotoxic T-lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death receptor 1/ programmed cell death ligand 1 (PD-1/PD-L1). Five patients (four males and one female) were treated with immune checkpoint inhibitors for advanced melanoma (stage III). None of them had prior history of autoimmune disorders, AIDS, or sarcoidosis. The PET/CT imaging studies showed new onset lymphadenopathy suspicious for malignancy. Four patients had cutaneous melanoma and one had vaginal melanoma. Three patients were treated with single agent (two Nivolumab, one Ipilimumab) and two with double agents (Ipilimumab and Pembrolizumab, or Ipilimumab and Nivolumab). PET/CT showed mediastinal multistational lymphadenopathy in four cases and peri-portal lymphadenopathy in one patient. Ultrasound-guided fine needle aspiration (FNA) biopsy showed numerous sarcoid-like granulomatous inflammation, while the fungal and mycobacterial infections were excluded. Cytomorphologically, the granulomas were numerous, mostly large, cellular and non-necrotizing. Multi-nucleated giant were rare or not seen at all. Cell blocks did not show any fibrosis. Other adverse effects included mouth sores, flu-like symptoms, arthritis, muscle aches, skin rashes, mild and severe colitis. The treatment was stopped and patients received prednisone. One patient developed severe adrenal insufficiency, which prolonged prednisone tapering. Their condition improved and lymphadenopathy was resolved in follow-up imaging. Sarcoid-like granulomatous inflammation is an adverse event in patients treated with immune checkpoint therapy such as Ipilimumab and Nivolumab. It can present as enlarged lymph nodes in PET/CT imaging suspicious for malignancy. FNA can serve as a minimally invasive tool to investigate the underlying cause of lymphadenopathy in this subset of patients.

Objective Immune checkpoint inhibitors (ICI) are transforming the field of oncology, leading to tumor regression in multiple advanced cancers. With this case series, we review the ultrasound imaging findings in a series of patients with ICI-induced inflammatory arthritis (IA), a novel rheumatic disease that is caused by cancer immunotherapy. Methods We identified patients with rheumatologist-diagnosed, ICI-induced IA who had musculoskeletal ultrasound performed for clinical care. A retrospective chart review was done to obtain demographics, oncologic history, clinical presentation, imaging, and synovial fluid results. Ultrasound images were reviewed and scored for synovial and tendon pathology, presence of Doppler, and bony erosion. Results Nine patients were included in this study with a total of 18 joint regions assessed. The knees were the most commonly imaged joint followed by the hands, wrists, feet, and ankles. Synovitis was seen in 12 of the 18 joints with active Doppler in 50% of the cases. Tendon involvement was also frequently seen (13 of 18 joints) with tenosynovitis, tendinitis, and enthesophytes. Erosions were less frequent and seen in only three cases but were also an early finding. Conclusion Patients with ICI-induced IA had a wide range of pathology affecting the synovium, tendons, and bones on musculoskeletal ultrasound. Further systematic study with imaging is needed for this group of diseases.

Background: Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (irAEs). Methods to obtain real-time multidisciplinary input for irAEs that require subspecialist care are unknown. This study aimed to determine whether a virtual multidisciplinary immune-related toxicity (IR-tox) team of oncology and medicine subspecialists would be feasible to implement, be used by oncology providers, and identify patients for whom multidisciplinary input is sought. Patients and Methods: Patients treated with ICIs and referred to the IR-tox team in August 2017 through March 2018 were identified. Feasibility was defined as receipt of electronic referrals and provision of recommendations within 24 hours of referral. Use was defined as the proportion of referring providers who used the team’s recommendations, which was determined through a postpilot survey. Demographics and tumor, treatment, and referral data were collected. Patient features and irAE associations were analyzed. Results: The IR-tox team was found to be feasible and used: 117 referrals from 102 patients were received in 8 months, all providers received recommendations within 24 hours, 100% of surveyed providers used the recommendations, and 74% changed patient management based on IR-tox team recommendations. Referrals were for suspected irAEs (n=106; 91%) and suitability to treat with ICIs (n=11; 10%). In referred patients, median age was 64 years, 54% were men, 13% had prior autoimmunity, and 46% received ICI combinations versus monotherapy (54%). The most commonly referred toxicities were pneumonitis (23%), arthritis (16%), and dermatitis (15%); 15% of patients had multisystem toxicities. Multiple referrals were more common in those treated with combination ICIs (odds ratio [OR], 6.0; P=.035) or with multisystem toxicities (OR, 8.1; P=.005). The IR-tox team provided a new multidisciplinary forum to assist providers in diagnosing and managing complex irAEs. This model identifies educational and service needs, and patients with irAEs for whom multidisciplinary care is most sought. Conclusions: A virtual multidisciplinary toxicity team for irAEs was a feasible and used service, and facilitated toxicity identification and management.

Background. Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with immune dysregulation and increased risk of infections. The presence of autoantibodies and immunoglobulin abnormalities indicates B-cell and antibody-secreting cell (ASC) dysfunction. We hypothesize that soluble factors associated with B-cell and ASC activity are decreased in RA patients and that this is linked to higher susceptibility to infections.Methods. Using the Johns Hopkins Arthritis Cohort and Biorepository, we contrasted serum protein levels of soluble factors involved in B-cell activation (CD40, CD40L) and B-cell/ASC homing (CXCL10, CXCL11, and CXCL13) or survival (BAFF, APRIL, TACI, and BCMA) in 10 healthy subjects and 23 adult RA patients (aged 24-65 years). We subdivided RA patients into those with (n=17) and those without infections (n=6) within a 2-year period. In order to reduce the effect of RA treatment, we only included patients receiving methotrexate monotherapy or no RA treatments at baseline. Soluble serum protein levels of B-cell/ASC factors were quantified by multiplex immunoassays.Results. We identified that (1) serum levels of soluble BCMA, APRIL, CD40, and CD40L were significantly decreased in RA patients relative to healthy individuals; (2) serum soluble BCMA, predominantly released by ASC, correlated with serum concentrations of class-switched immunoglobulins, IgG and IgA; and (3) RA patients with a history of infections had significantly lower soluble BCMA levels compared with healthy donors and with RA patients without infections.Conclusions. Our study using soluble factors linked to B-cell/ASC activation and survival suggests that there is a paucity of ASC in a subset of RA patients and that this may be linked to altered antibody production and increased risk of infections. Further delineating the link between ASC and infection susceptibility in RA may optimize disease management and provide novel insights into disease pathogenesis that are susceptible to intervention.

Background The objective of this study was to characterize the clinicopathologic features of sicca syndrome associated with immune checkpoint inhibitor (ICI) therapy. Subjects, Materials, and Methods Consecutive patients with new or worsening xerostomia in the setting of ICI treatment for benign or malignant neoplastic disease were evaluated, including labial salivary gland biopsy (LSGB). Results Twenty patients (14 male; median age 57 years) had metastatic melanoma (n = 10), metastatic carcinoma (n = 6), or recurrent respiratory papillomatosis (n = 4) and were being treated with avelumab (n = 8), nivolumab (n = 5), pembrolizumab (n = 4), nivolumab/ipilimumab (n = 2), and M7824, a biologic targeting programmed cell death ligand 1 (PD-L1) and transforming growth factor ß (n = 1). Four had pre-existing autoimmune disease. Nineteen had very low whole unstimulated saliva flow; six had new dry eye symptoms. The median interval between ICI initiation and dry mouth onset was 70 days. Rheumatoid factor and anti-Sjögren's Syndrome-related Antigen A (Anti-SSA) were both positive in two subjects. LSGB showed mild-to-severe sialadenitis with diffuse lymphocytic infiltration and architectural distortion. There were lymphocytic aggregates in eight patients, composed mainly of CD3+ T cells with a slight predominance of CD4+ over CD8+ T cells. ICI targets (e.g., programmed cell death 1 and PD-L1) were variably positive. In direct response to the advent of the sicca immune-related adverse event, the ICI was held in 12 patients and corticosteroids were initiated in 10. Subjective improvement in symptoms was achieved in the majority; however, salivary secretion remained very low. Conclusion ICI therapy is associated with an autoimmune-induced sicca syndrome distinct from Sjögren's syndrome, often abrupt in onset, usually developing within the first 3 months of treatment, and associated with sialadenitis and glandular injury. Improvement can be achieved with a graded approach depending on severity, including withholding the ICI and initiating corticosteroids. However, profound salivary flow deficits may be long term. Implications for Practice Sicca syndrome has been reported as an immune-related adverse event (irAE) of immune checkpoint inhibitor therapy (ICI) for neoplastic diseases. Severe dry mouth (interfering with eating or sleeping) developed abruptly, typically within 90 days, after initiation of ICI therapy. Salivary gland biopsies demonstrated mild-to-severe sialadenitis distinct from Sjögren's syndrome, with diffuse T-cell lymphocytic infiltration and acinar injury. Recognition of the cardinal features of ICI-induced sicca will spur appropriate clinical evaluation and management, including withholding of the ICI and corticosteroid, initiation. This characterization should help oncologists, rheumatologists, and oral medicine specialists better identify patients that develop ICI-induced sicca to initiate appropriate clinical evaluation and therapy to reduce the likelihood of permanent salivary gland dysfunction.

Background 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. Case presentations 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. Conclusions 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.

Immune checkpoint inhibitors (ICIs) are the standard of care for the treatment of several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks of toxicity, specifically immune-related adverse events (irAEs). There is a need for clear, effective guidelines for the management of irAEs during ICI treatment, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of single and combination ICI irAEs and ultimately developed evidence- and consensus-based recommendations to assist medical professionals in clinical decision-making and to improve outcomes for patients.

BACKGROUND: Dermatoses are common and potentially serious complications of programmed cell death receptor PD-1 immune checkpoint inhibitor (anti-PD-1 ICI) therapy. Understanding their incidence is necessary to support clinical awareness, diagnosis, and management. OBJECTIVE: To examine the incidence and odds of reported non-cancerous dermatoses in the setting of anti-PD-1 ICI therapy. METHODS: Cross-sectional study of anti-PD-1 (pembrolizumab or nivolumab) treated patients at a tertiary healthcare institution. Selected dermatologic events following immunotherapy were identified in the electronic medical record. Comparator arm were patients that developed these same dermatoses without receiving anti-PD-1 ICI therapy. RESULTS: There were 13.7% (254/1857) patients that developed one of 28 dermatoses. Compared with the general population, patients treated with anti-PD-1 had a greater risk for development of mucositis (OR 65.7, 95% CI 35.0–123.3), xerostomia (OR 11.9, 95% CI 8.4–16.8), pruritus (11.3, 95% CI 8.9–14.3), and lichen planus/lichenoid dermatitis (OR 10.7, 95% CI 5.6–20.7). CONCLUSIONS: We report the frequency of dermatoses encountered in the setting of ICI therapy, both common (pruritus, rash, vitiligo) and uncommon (scleroderma, urticaria).

Immune checkpoint inhibitors (ICI) cause a variety of adverse events due to increased immune activation. Inflammatory arthritis is the most common side effect of ICIs seen by rheumatologists. Inflammatory arthritis can have heterogeneous presentations, but, most commonly, presents as an oligoarthritis or polyarthritis. Tendons may also be involved, and imaging shows a variety of changes, including synovitis, joint effusions, tenosynovitis, enthesitis, tendinitis, and enthesophytes. Treatments include nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, intra-articular corticosteroids, conventional synthetic disease modifying drugs (e.g., methotrexate), and biologics, depending on severity and persistence of the arthritis. More studies are needed, but preliminary data do not show increased tumor progression in patients who require these therapies.

Background Tumor-specific antibodies have been reported in patients with cancers responding to immune checkpoint inhibitors (ICI), and there is an increasing appreciation for the potential role of B cells in mediating ICI responses. However, the humoral immune response to melanoma remains incompletely defined. We hypothesized that screening sera for antibodies by immunoprecipitation with lysates of cultured melanoma cells would increase the likelihood of detecting circulating antibodies in melanoma patients receiving ICI, and potentially identify novel antibody targets associated with treatment response and/or immune-related adverse events (IRAEs). Methods Pre-and on/post-treatment sera or plasma from 12 clinically-annotated patients with advanced metastatic melanoma receiving ICI were assayed for tumor-specific antibodies with an established immunoprecipitation platform. 35S-methionine-labeled lysates from cultured 624Mel cells were used for immunoprecipitation. 624Mel expresses several shared non-mutated melanoma antigens (e.g., MAGEA3, tyrosinase, MART-1/Melan-A, gp75, and gp100). Antigen identity was determined using on-bead digests followed by mass spectrometry, and was confirmed by immunoprecipitation with in vitro transcription/translation (IVTT) products. Results Antibodies reactive against 624Mel proteins were detected in 4 of 12 (33%) patients (table 1). Mass spectrometric sequencing performed on proteins captured with sera from 3 of 4 patients identified several putative antigens. Immunoprecipitation with IVTT candidate proteins confirmed antibodies against melanoma-associated and cancer testis antigens NY-ESO-1, SSX2 and MAGEA10. Antibodies were observed in 1 of 1 (100%) patient with a complete response, 2 of 4 (50%) with a partial response, 1 of 1 (100%) with stable disease, and 0 of 6 (0%) with progressive disease. Antibody levels varied over the course of therapy, with previously undetectable specificities arising during treatment response in patients #1–3. Patient #1 with a complete tumor regression developed antibodies to SSX2 and MAGEA10 that were absent before treatment. Further, detection of these antibodies coincided with diagnosis of IRAEs (anti-SSX2 with pancreatitis and anti-MAGEA10 with dermatitis). In contrast, patient #3, initially with a partial tumor regression, demonstrated a loss of detectable anti-NY-ESO-1 antibodies upon disease progression, and subsequent metastasectomy demonstrated loss of NY-ESO-1 protein expression in the progressing tumor. Testing sera from all 12 patients with IVTT products for NY-ESO-1, SSX2 and MAGEA10 did not reveal additional humoral responses. Conclusions Our comprehensive screening platform detected circulating antibodies specific to multiple melanoma-associated and cancer testis antigens in patients deriving clinical benefit from ICI. Expanded investigations of the evolution of antibody production over the course of ICI therapy, associated with tumor response to treatment and development of IRAEs, are warranted. Acknowledgements This study was supported by the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, and NIH P30-AR070254. Ethics Approval This study was approved by the Johns Hopkins Institutional Review Board, approval #NA_00090257.

Background Cutaneous toxicities are a common and potentially serious complication of programmed cell death receptor PD-1 immune checkpoint inhibitor (anti-PD-1 ICI) therapy. These cutaneous immune-related adverse events (irAEs) have been reported in up to one-third of treated patients, and are usually the first adverse event to occur with immune checkpoint inhibitor use. Due to non-specific reporting in many anti-PD-1 clinical trials, little data is available on the real-world incidence and morphology of cutaneous irAEs. Understanding the spectrum of cutaneous adverse events in real-world clinical environments is necessary to support clinical awareness, diagnosis, and management when undergoing anti-PD-1 therapy. We aimed to describe the incidence of a known spectrum of skin dermatoses in the setting of ICI, and also identify the risk of these adverse events compared with the general population. Methods This was a cross-sectional study of anti-PD-1 (pembrolizumab or nivolumab) treated patients at a tertiary healthcare institution from September 2014 to November 2018. Inflammatory dermatoses occurring in the setting of anti-PD-1 therapy (pembrolizumab or nivolumab) was compiled using our institutional experience with ICIs and case studies and reports on PUBMED. Selected dermatologic events following immunotherapy were identified in the electronic medical record. Unadjusted odds ratios (OR) for the development of a given cutaneous event was calculated by comparison to the non-ICI general population. Results Of the 1,857 patients treated with anti-PD-1 ICIs, there were 1,079 patients treated with nivolumab, 821 patients treated with pembrolizumab, and 43 patients treated with both pembrolizumab and nivolumab. There were 254/1857 (13.7%) patients that developed one of the 28 different dermatoses identified from literature review following anti-PD-1 ICIs. Compared with the general population, patients treated with anti-PD-1 had a greater risk for development of mucositis (OR 65.7, 95% CI 35.0-123.3), xerostomia (OR 11.9, 95% CI 8.4-16.8), pruritus (11.3, 95% CI 8.9-14.3), and lichen planus/lichenoid dermatitis (OR 10.7, 95% CI 5.6-20.7) compared to the control group. Conclusions We report the frequency of dermatoses encountered in the setting of ICI therapy, both commonly (pruritus, rash, vitiligo) and more rarely reported (scleroderma, urticaria). As nivolumab and pembrolizumab currently make the bulk of approvals for ICI therapy, this analysis of real-world irAE incidence will be of use to treatment teams to improve quality of life and ensure ICI therapy adherence. Furthermore, this analysis sets the stage for future in-depth investigation of these cutaneous toxicities, including dose-response relationships, prognostic information from cutaneous events, and optimal treatment strategies. Ethics Approval This study did not require IRB approval, due to the use of anonymized and de-identified aggregate-level data.

Rheumatologists increasingly receive consults for patients treated with immune checkpoint inhibitors (ICIs) for cancer. ICIs can cause inflammatory syndromes known as immune-related adverse events (IRAEs). Several rheumatic IRAEs have been reported, including inflammatory arthritis, polymyalgia rheumatica, and myositis. For patients who present with musculoskeletal symptoms while receiving ICI therapy, it is important to have an algorithm for evaluation. The differential diagnosis includes a range of musculoskeletal syndromes, such as crystalline arthritis, mechanical issues, and osteoarthritis, in addition to IRAEs. After diagnosing a rheumatic IRAE, rheumatologists must work with the patient and the oncologist to form a treatment plan. Treatment of IRAEs is guided by severity. Evidence for management is limited to observational studies. Inflammatory arthritis and polymyalgia rheumatica are treated with nonsteroidal antiinflammatory drugs in mild cases, glucocorticoids for moderate-to-severe cases, and sometimes require other disease-modifying antirheumatic drugs. Myositis due to ICIs can be accompanied by myocarditis or myasthenia gravis. Glucocorticoids and withholding the ICI are usually required to treat myositis; some patients with severe myositis require intravenous immunoglobulin or plasmapheresis. Further research is needed to optimize treatment of IRAEs that does not compromise the antitumor effect of ICIs.

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. Methods IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable-adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long-term (malignancy and death) events. VTEs were assessed descriptively. Results For MACE, SIEs, and HZ, 1999 (3152.1 patient-years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient-years) and 6354 (16 670.8 patient-years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS-trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43-3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13-0.54) and 0.33 (0.24-0.45) for tofacitinib and bDMARDs, respectively. Conclusion In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.

Purpose of review This review summarizes the current evidence on treatment strategies for inflammatory arthritis because of cancer treatment with immune checkpoint inhibitors (ICI), prognosis of ICI-induced arthritis, and management of patients with preexisting inflammatory arthritis receiving ICI therapy. Recent findings Inflammatory arthritis is the most common rheumatic immune-related adverse event observed in patients receiving ICI therapy. Most patients can successfully be treated with low doses of corticosteroids or conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). A small minority will develop severe symptoms requiring biologic therapy including TNF inhibitors and IL-6 receptor inhibitors. Many cases of inflammatory arthritis will resolve with cessation of ICI therapy. Some patients will develop persistent arthritis despite discontinuation. Patients with preexisting inflammatory arthritis (e.g. rheumatoid arthritis) commonly flare on ICI therapy, but can usually be managed with corticosteroids. Summary Inflammatory arthritis following ICI therapy for cancer is relatively common and the practicing rheumatologist should be able to recognize and manage it in conjunction with Oncology. The majority of patients respond to corticosteroids, but some will need treatment with conventional synthetic or biologic DMARDs. Additional studies should investigate the effects of immunosuppression on tumor response and the use of ICI therapy in patients with preexisting autoimmune disease.

We were interested to read the letter by Ceccarelli et al regarding their experience with Immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA) at Sapienza University.1 Their findings support that ICI-induced IA is a heterogeneous disease with differing outcomes. The differences in the cohorts studied may also give us insight into the risk factors …

Objective Immune checkpoint inhibitors (ICIs) are improving prognoses in advanced stage cancers, but they also lead to immune-related adverse events (IRAEs). IRAEs targeting many organ systems have been reported, but musculoskeletal and rheumatic IRAEs have not been well-characterized. We systematically reviewed published literature on musculoskeletal and rheumatic IRAEs to better understand prevalence and clinical characteristics. Methods Medline and CENTRAL databases were searched for articles reporting rheumatic and musculoskeletal IRAEs secondary to ICI treatment. After screening abstracts and full texts in duplicate, clinical features, prevalence, and treatment data were extracted and summarized. Results A total of 1,725 unique abstracts were screened; 231 contained original data and were about ICIs and went to full-text screening. Fifty-two of these contained information about musculoskeletal or rheumatic IRAEs or about treatment with ICIs in preexisting autoimmune disease. Of these, 33 were clinical trials, 3 were observational studies, and 16 were case reports or series. Arthralgia prevalence in clinical trials ranged 1–43%, and myalgia was reported in 2–20%. Arthritis was reported in 5 of 33 clinical trials, and vasculitis was reported in only 2. One observational study and 3 case reports described patients with preexisting autoimmune disease treated with ICIs. Case reports included development of inflammatory arthritis, vasculitis, myositis, and lupus nephritis. Conclusion Arthralgia and myalgia have been reported commonly in patients treated with ICIs. The prevalence of rheumatic IRAEs such as inflammatory arthritis, vasculitis, and sicca syndrome is less clear from current evidence. There is limited observational and case-level evidence describing ICI use in patients with preexisting autoimmune disease.

This commentary summarizes current knowledge on the clinical presentation, management, and outcomes of the inflammatory arthritis which may occur as an immune-related adverse evet of immune checkpoint inhibitor therapy. Herein, we propose a new algorithm aimed at assisting oncologists in the diagnosis and management of this immune-related adverse event.

Immune checkpoint inhibitors (ICIs) are being increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAE). Some IRAE including inflammatory arthritis, sicca syndrome, myositis and vasculitis are of special interest to rheumatologists. As use of ICIs increases, recognition of these IRAEs and developing treatment strategies will become important. In this review, the current literature on rheumatic and musculoskeletal IRAEs is summarized. The incidence, clinical presentations, and treatment considerations are highlighted.

ObjectiveWe sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies.MethodsWe conducted a prospective observational study of patients referred for IA associated with ICIs. Patients were recruited from June 2015 to December 2018. Information was obtained at the baseline visit, and follow-up visits occurred at varying intervals for up to 24 months from ICI cessation. Kaplan-Meier curves were developed to characterise IA persistence. Cox proportional hazards models were used to assess the influence of various factors on IA persistence. Logistic regression was used to evaluate the impact of IA treatment on tumour response.ResultsSixty patients were monitored with a median follow-up after ICI cessation of 9 months. A majority (53.3%) had active IA at their most recent follow-up. IA was less likely to improve in those with longer duration of ICI use, in those receiving combination ICI therapy, and in patients with multiple other immune-related adverse events. Tumour response did not appear to be impacted by immunosuppression. Although not statistically significant, persistent IA was correlated with a better tumour response (complete or partial response).ConclusionICI-induced IA can become a long-term disease necessitating management by rheumatology for immunomodulatory treatment. Importantly, the use of immunomodulatory treatment has not been shown to impact cancer outcomes in this study.

Background Checkpoint inhibitor therapy has caused a paradigm shift in the field of oncology, producing significant survival benefits in patients with an ever-growing list of malignancies, but their use is attended by a spectrum of immune related adverse events (irAEs). Many rheumatic irAEs have been described. A critical and presently unanswered question is what proportion of these rheumatic irAEs represent new appearances of classic rheumatic diseases or, alternatively, represent new clinical variants with potentially different pathogenesis, clinical course and treatment responsiveness. Little is known about the PMR-like entity that has been described in the setting of ICI therapy. Objectives To assess whether the polymyalgia rheumatica (PMR)-like syndrome reported as an irAE from checkpoint inhibitor therapy is consistent with the 2012 EULAR/ACR provisional criteria for PMR1. Methods The cases were derived from two sources. Group 1 represents reported cases from three contributing centers. Group 2 was derived from a systematic review of the literature searching for all cases reported as PMR or PMR-like illness associated with checkpoint inhibitor therapy. Cases were assessed for the quality of reporting and then analyzed to determine whether they fulfilled the 2012 EULAR/ACR provisional criteria for PMR. Results A total of 49 patients were included for analysis, including 9 cases from Cleveland Clinic (Table 1), 4 cases from Johns Hopkins University, and 7 cases from University Hospital of Bordeaux, in addition to the 29 separate cases found by systematic review. Among the entire group, 37 (75%) were designated “complete” indicating that they had sufficient data to reliably apply the 2012 EULAR/ACR criteria of which 28 (75%) cases fulfilled complete criteria for PMR. A number of cases also demonstrated some clinical features unusual for idiopathic PMR. Conclusion This study suggests a high proportion of reported cases of checkpoint inhibitor-related PMR fulfill preliminary criteria for PMR yet in one quarter clinical details were incomplete making verification problematic. Furthermore, in the absence of a gold standard for the diagnosis of PMR, the relationship of checkpoint inhibitor-related PMR to the idiopathic form remains unclear. References [1] Dasgupta B, Cimmino MA, Maradit-Kremers H, et al. 2012provisional classification criteria for polymyalgia rheumatic: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis2012;71:484-492. Disclosure of Interests cassandra calabrese Speakers bureau: Regeneron/Sanofi, Laura Cappelli Grant/research support from: Bristol-Myers Squibb, Consultant for: Regeneron/Sanofi Genzyme, Marie Kostine: None declared, Elizabeth Kirchner Consultant for: Celgene, Horizon, Novartis, Regeneron, Speakers bureau: Merck and Sanofi, Tawnie Braaten Grant/research support from: supported by T32 grant and “research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number T32AR048522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”, Leonard Calabrese Consultant for: Bristol-Myers-Squibb, Genentech and Astra-Zeneca.

Background: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Real-world data (RWD) complement clinical trial data in assessing long-term safety. To our knowledge, this is the first long-term comparative RWD analysis of tofacitinib. Objectives: To compare 5-year adverse event (AE) incidence rates (IRs) in patients (pts) starting tofacitinib vs biological (b)DMARDs using cohorts from the US Corrona RA registry. Methods: This prospective, observational 5-year study embedded in the ongoing US Corrona RA registry routinely collected 9 categories of predefined AEs from participating physicians. Real-world safety event rates of major adverse cardiovascular events (MACE), serious infectious events (SIEs) and herpes zoster (HZ; serious and non-serious) were compared in pts with RA who started tofacitinib or a bDMARD regardless of dose/schedule between 6 Nov 2012 (US FDA approval) and 30 Jun 2017 (follow-up through 31 Dec 2017). Endpoints were selected a priori as having sufficient power to detect a 2-fold difference between cohorts at this datacut; there was insufficient power to assess malignancy. Baseline variables with a standardised difference >│0.10│ between tofacitinib and bDMARD initiators, and a priori selected covariates (gender, age, line of therapy, history of AE of interest) were used to construct propensity scores (PS) to derive a PS-trimmed (primary) population and a PS–matched population for sensitivity analysis (ratio: max. 4 bDMARD:1 tofacitinib; calliper=0.05). Pts were followed from initiation until an AE of interest, discontinuation and/or start of a new therapy +90 days, death or end of follow-up, whichever came first. Crude IRs (events/100 pt–years [PY]) were estimated; multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) comparing rates of first events between cohorts. Results: In total, 1544 tofacitinib (2138.2 PY) and 7083 bDMARD (9904.9 PY) initiators were included. PS–trimming resulted in 1117 tofacitinib and 5542 bDMARD initiators. Rates of MACE and SIEs were similar in both cohorts (Fig 1A); adjusted HRs (95% confidence intervals [CIs]) were: MACE 0.60 (0.30, 1.18); SIEs 0.99 (0.72, 1.36; Fig 1B). HZ IR was higher for tofacitinib vs bDMARDs (Fig 1A); HRs for HZ were significantly increased with tofacitinib vs bDMARDs (adjusted HR 2.12 [1.22, 3.66]; Fig 1B); all HZ events were non-serious with tofacitinib. Similar results were observed in PS-matched populations. Conclusion: This is the first comparative analysis of RWD for tofacitinib and bDMARDs to use PS-trimmed and PS-matched analyses to adjust for channelling/prescribing patterns for newly approved therapies. Pts starting tofacitinib or bDMARDs for RA had similar rates of MACE and SIEs. Tofacitinib initiators had higher HZ IRs vs bDMARD initiators. These results are consistent with long-term clinical trial findings. Acknowledgement: Sponsors: Corrona, LLC. Corrona is supported by contracted subscriptions with multiple companies. This was a Corrona/Pfizer collaboration with Pfizer financial support. Medical writing support provided by Anthony G McCluskey of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Joel Kremer Grant/research support from: AbbVie, Genentech, Lilly, Novartis, Pfizer, Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Regeneron, Sanofi, Pfizer, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Laura Cappelli Grant/research support from: Bristol-Myers Squibb, Consultant for: Regeneron/Sanofi Genzyme, Carol Etzel Shareholder of: Corrona, LLC, Consultant for: Merck, Employee of: Corrona, LLC, Jeffrey Greenberg Shareholder of: Corrona, LLC, Consultant for: Eli Lilly, Genentech, Janssen, Novartis, and Pfizer Inc, Employee of: Corrona, LLC, Jamie Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ann Madsen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Connie Chen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alina Onofrei Employee of: Corrona, LLC, Christine Barr Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, Dimitrios A Pappas Grant/research support from: AbbVie, Consultant for: AbbVie, Employee of: Corrona, Heather J. Litman: None declared, Kimberly J Dandreo Employee of: Corrona, LLC, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Carol A. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arthur Kavanaugh Grant/research support from: UCB Pharma