Development of an Educational Website for Patients With Cancer and Preexisting Autoimmune Diseases Considering Immune Checkpoint Blockers: Usability and Acceptability Study.

BACKGROUND: Patients with cancer and an underlying autoimmune disease who are considering immune checkpoint blockers (ICBs) need to know about the benefits and risks of severe immune-related adverse events and flares of the autoimmune condition. OBJECTIVE: This study aims to develop and alpha test an educational website for patients with cancer. METHODS: Learning topics, images, and website architecture (including flow and requirements) were developed and iteratively reviewed by members of a community scientist program, a patient advisory group, and content experts. Alpha testing was performed, measuring the site's usability using the Suitability Assessment of Materials and its acceptability using the Ottawa Acceptability Measure. RESULTS: The website included a home page; general information about ICBs; comprehensive modules on the benefits and risks of ICBs for patients with cancer and preexisting autoimmune diseases; general wellness information; and features such as a quiz, additional resources, and a glossary. For the alpha testing, 9 users assessed the newly developed website. Patient reviewers (n=5) had rheumatoid arthritis, Crohn disease, Sjogren syndrome, or vasculitis. Health care provider reviewers (n=4) were medical oncologists or rheumatologists. The median Suitability Assessment of Materials rating was 75 (IQR 70-79; range 0-100) for patients versus 66 (IQR 57-72; range 0-100) for providers (scores ≥70 indicate no substantial changes needed). Recommendations for improvement, mostly involving navigation and accessibility, were addressed. All participants expressed that the website was acceptable and balanced in terms of discussion of benefits and harms. Because half (2/4, 50%) of the providers suggested we increase the amount of information, we extended the content on the impact of having an autoimmune disease when considering ICB treatment, the probability of flares, and the management of flares in this context. CONCLUSIONS: The feedback led to minor revisions to enhance readability, navigation, and accessibility, ensuring the website's suitability as a decision-making aid. The newly developed website could become a supporting tool to facilitate patient-physician discussion regarding ICBs.

Trends in the use of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and recently diagnosed colorectal, lung, or prostate cancer.

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer. METHOD: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic regression. Cancer cohorts were analyzed separately. RESULTS: We included 3595 patients in all six cohorts (in Clinformatics® 503 with colorectal, 468 with lung, and 440 with prostate cancer; in SEER-Medicare 580 with colorectal, 1010 with lung, and 594 with prostate cancer). No significant increase was observed in bDMARD or TNFi utilization over time. Overall, use of bDMARD within the first 3 years of follow-up ranged from 16.7% (Clinformatics® lung cohort) to 29.7% (SEER-Medicare colorectal cohort). The major predictor of bDMARD utilization was prior use in the 3 months before cancer diagnosis (p < 0.001 for all cancers) and earlier cancer stage (p < 0.001 in colorectal and lung cancer and p = 0.05 in prostate cancer). CONCLUSIONS: Use of bDMARD in patients with RA and recently diagnosed common cancers has not increased since 2008. Additional evidence on the safety of bDMARD in patients with early cancer is needed to ensure appropriate management of their RA. Key Points • Use of bDMARD and TNFi in patients with RA and early colorectal, lung, or prostate cancer has been stable since 2008, with no significant increases over time. • The major determinant of receiving bDMARD after cancer diagnosis was prior treatment with bDMARD in the prior 3 months before cancer. • Patients with advanced cancer stage and distant metastases were less likely to receive bDMARD and TNFi than those at early stages of disease.

Survival in patients with rheumatoid arthritis and early breast cancer treated with tumor necrosis factor inhibitors.

BACKGROUND: There have been concerns about the use of tumor necrosis factor inhibitors (TNFi) for autoimmune disease in patients with recently diagnosed cancer. We assessed the survival of patients with rheumatoid arthritis (RA) and newly diagnosed early breast cancer (BC) treated with TNFi in the first two years after BC diagnosis. METHODS: We identified patients in two datasets: (1) Optum's de-identified Clinformatics® Data Mart Database (CDM), (2) Surveillance, Epidemiology, and End Results program (SEER) and Texas Cancer Registry (TCR) Medicare-linked cohort. We grouped patients according to whether they received TNFi, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) only, or no DMARDs within 2 years after BC. Outcomes were overall survival (OS) and BC-specific survival (BCSS). We conducted landmark analyses at years 1 and 2, with multivariable Cox regressions using propensity scores for adjustment. RESULTS: In the first year after BC, 165/970 (17.0%) and 201/1246 (16.1%) patients received TNFi in CDM and SEER/TCR-Medicare respectively. In the 1 year landmark, no significant differences in OS were observed between patients treated with TNFi and patients treated with csDMARDs only in CDM (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.42-1.40) or SEER/TCR-Medicare (HR = 0.84, 95% CI 0.54-1.31). BCSS (SEER/TCR-Medicare) was better in patients receiving TNFi than in those receiving csDMARDs only (HR = 0.28, 95% CI 0.08-0.98). In CDM, glucocorticoid therapy had worse OS than those without glucocorticoids (HR = 2.18, 95% CI 1.13-4.18). This was also observed in SEER/TCR-Medicare (not statistically significant). Similar results were observed for the 2 year landmark. CONCLUSIONS: TNFi treatment during the first two years after early BC was not associated with worse survival.

A systematic review and meta-analysis of observational studies and uncontrolled trials reporting on the use of checkpoint blockers in patients with cancer and pre-existing autoimmune disease.

BACKGROUND: Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs. METHODS: We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths. RESULTS: A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease. CONCLUSIONS: Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.

Opioid Treatment for Adults With and Without Systemic Autoimmune/Inflammatory Rheumatic Diseases: Analysis of 2006-2019 United States National Data.

OBJECTIVES: This study compared opioid prescribing among ambulatory visits with systemic autoimmune/inflammatory rheumatic diseases (SARDs) or without and assessed factors associated with opioid prescribing in SARDs. METHODS: This cross-sectional study used the National Ambulatory Medical Care Survey between 2006 and 2019. Adult (≥18 years) visits with a primary diagnosis of SARDs, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or systemic lupus erythematosus were included in the study. Opioid prescribing was compared between those with vs without SARDs using multivariable logistic regression accounting for the complex survey design and adjusting for predisposing, enabling, and need factors within Andersen's Behavioral Model of Health Services Use. Another multivariable logistic regression examined the predictors associated with opioid prescribing in SARDs. RESULTS: Annually, an average of 5.20 million (95% confidence interval [CI] 3.58-6.82) visits were made for SARDs, whereas 780.14 million (95% CI 747.56-812.72) visits were made for non-SARDs. The SARDs group was more likely to be prescribed opioids (22.53%) than the non-SARDs group (9.83%) (adjusted odds ratio [aOR] 2.65; 95% CI 1.68-4.18). Among the SARDs visits, patient age from 50 to 64 (aOR 1.95; 95% CI 1.05-3.65 relative to ages 18-49) and prescribing of glucocorticoids (aOR 1.75; 95% CI 1.20-2.54) were associated with an increased odd of opioid prescribing, whereas private insurance relative to Medicare (aOR 0.50; 95% CI 0.31-0.82) was associated with a decreased odds of opioid prescribing. CONCLUSION: Opioid prescribing in SARDs was higher compared to non-SARDs. Concerted efforts are needed to determine the appropriateness of opioid prescribing in SARDs.

Factors Associated With Adherence of Cervical Cancer Screening in Women With Systemic Lupus Erythematosus.

OBJECTIVE: The objective is to determine cervical cancer screening rates and factors associated with decreased cervical cancer screening in women with systemic lupus erythematosus (SLE). METHODS: We conducted a cross-sectional study that enrolled consecutive women (age 21-64 years) with SLE. We collected demographics, clinical characteristics, constructs of the Health Beliefs Model (HBM) (ie, susceptibility, severity, barriers, benefits, cues to action, and self-efficacy), and self-reported cervical cancer screening (confirmed with the electronic medical record). The primary outcome was adherence to cervical cancer screening according to current guidelines. Multivariable logistic regression models were used to examine the association between SLE disease activity and cervical cancer screening and explore mediation effects from HBM constructs. RESULTS: We enrolled 130 women with SLE. The median age was 42 years (interquartile range 32-52 years). The cervical cancer screening adherence rate was 61.5%. Women with high SLE disease activity were less likely to have cervical cancer screening versus those with low disease activity (odds ratio 0.59, 95% confidence interval [CI] 0.39-0.89; P = 0.01), which remained statistically significant after adjusting for baseline demographics and drug therapy in a multivariable model (odds ratio 0.25, 95% CI 0.08-0.79; P = 0.02). Regarding the HBM constructs, increased perceived barriers to cervical cancer screening (r = -0.30, P < 0.01) and decreased self-efficacy (r = -0.21, P = 0.02) correlated with decreased cervical cancer screening. CONCLUSION: Patients with SLE with high disease activity undergo cervical cancer screening less frequently than those with low disease activity. Perceived barriers to cervical cancer screening are moderately correlated with decreased screening. These data highlight the need to develop strategies to increase cervical cancer screening in this high-risk patient population.

Mimickers of Immune Checkpoint Inhibitor-induced Inflammatory Arthritis.

The differential diagnosis of inflammatory arthritis as an immune-related adverse event can be challenging as patients with cancer can present with musculoskeletal symptoms that can mimic arthritis because of localized or generalized joint pain. In addition, immune checkpoint inhibitors can exacerbate joint conditions such as crystal-induced arthritis or osteoarthritis, or induce systemic disease that can affect the joints such as sarcoidosis. This distinction is important as the treatment of these conditions can be different from that of immune-related inflammatory arthritis.

Immune Checkpoint Inhibitor-induced Myositis.

Myositis induced by immune checkpoint inhibitors (ICIs) is an infrequent, potentially fatal, immune-related adverse event. It has higher incidence in patients who receive combination ICI therapy compared to monotherapy. Patients can present with clinical manifestation symptoms of myositis alone or in combination with myocarditis and/or myasthenia gravis, which significantly worsens the course and prognosis. Diagnosis can generally be made on the basis of clinical presentation, elevation of muscle enzymes, and electromyographic changes, but some patients may require a muscle biopsy. The first line of therapy is high-dose corticosteroids, followed by immunosuppression, plasmapheresis, or intravenous immunoglobulin in patients with severe disease.

Consensus on the definitions and descriptions of the domains of the OMERACT Core Outcome Set for shared decision making interventions in rheumatology trials.

OBJECTIVE: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions. METHODS: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains. RESULTS: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains. CONCLUSION: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set for trials of SDM interventions.

Rheumatic adverse events of immune checkpoint inhibitors in cancer immunotherapy.

INTRODUCTION: The advent of immune checkpoint inhibitors (ICIs) in cancer treatment has marked a transformative era, albeit tempered by immune-related adverse events (irAEs), including those impacting the musculoskeletal system. The lack of precise epidemiologic data on rheumatic irAEs is attributed to factors such as potential underrecognition, underreporting in clinical trials, and the tendency to overlook manifestations without immediate life-threatening implications, further complicating the determination of accurate incidence rates, while the complete understanding of the mechanisms driving rheumatic irAEs remains elusive. AREAS COVERED: This literature review comprehensively examines rheumatic irAEs in cancer patients undergoing ICI therapy, encompassing epidemiology, risk factors, mechanisms, clinical manifestations, and current management guidance for prevalent conditions such as inflammatory arthritis, polymyalgia rheumatica, and myositis. Less frequent rheumatic and musculoskeletal irAEs are also explored, alongside insights into ongoing clinical trials testing therapeutic and preventive strategies for irAEs. A thorough literature search on Medline and the National Cancer Institute Clinical Trials Database was conducted up to October 2023 to compile relevant information. EXPERT OPINION: In light of the evolving landscape of cancer immunotherapy, there is a compelling need for prospective longitudinal studies to enhance understanding and inform clinical management strategies for rheumatic irAEs.

Utilization of Biologic Disease-Modifying Antirheumatic Therapy in Patients With Rheumatoid Arthritis and Recently Diagnosed Breast Cancer.

OBJECTIVE: Biologic disease-modifying antirheumatic drugs (bDMARDs) are immunosuppressants, and there have been concerns that they might impact tumor immunity in patients with cancer with rheumatoid arthritis (RA). The purpose of this study was to describe the utilization trends of bDMARD in patients with RA after breast cancer (BC) diagnosis. METHODS: We performed a retrospective cohort study of adults with RA and BC (2008 onward) from Optum's de-identified Clinformatics® Data Mart Database (CDM); the Surveillance, Epidemiology, and End Results Program (SEER) Medicare; and the Texas Cancer Registry (TCR) Medicare databases. We evaluated bDMARD utilization trends during the first three years after BC. We conducted multivariable logistic regression to evaluate the association of utilization with patient characteristics. RESULTS: A total 1,412 patients were identified in CDM and 1,439 patients in SEER/TCR-Medicare. During the three months before BC diagnosis, 28.2% (CDM) and 26.9% (SEER/TCR-Medicare) patients had received bDMARDs. Within the first three years after diagnosis, 24.1% (CDM) and 26.4% (SEER/TCR-Medicare) were receiving bDMARDs. About 70% of the patients in the two cohorts received glucocorticoids with no significant time trend increases. The largest predictor of bDMARD utilization was prior use before BC (CDM: odds ratio [OR] 27.15, 95% confidence interval [CI] 19.29-38.19; SEER/TCR: OR 18.98, 95% CI 13.72-26.26). Regional and distant BC compared to in situ or localized were also associated with lower bDMARDs utilization in SEER/TCR-Medicare (OR 0.54, 95% CI 0.36-0.82; OR 0.31, 95% CI 0.13-0.77, respectively). CONCLUSION: The utilization of tumor necrosis factor inhibitors and other bDMARDs in patients with RA and recent BC has not increased since 2008. Glucocorticoids utilization remained high. The largest predictor of bDMARD utilization was prior use before BC.

OMERACT Core outcome measurement set for shared decision making in rheumatic and musculoskeletal conditions: a scoping review to identify candidate instruments.

OBJECTIVES: Shared decision making (SDM) is a central tenet in rheumatic and musculoskeletal care. The lack of standardization regarding SDM instruments and outcomes in clinical trials threatens the comparative effectiveness of interventions. The Outcome Measures in Rheumatology (OMERACT) SDM Working Group is developing a Core Outcome Set for trials of SDM interventions in rheumatology and musculoskeletal health. The working group reached consensus on a Core Outcome Domain Set in 2020. The next step is to develop a Core Outcome Measurement Set through the OMERACT Filter 2.2. METHODS: We conducted a scoping review (PRISMA-ScR) to identify candidate instruments for the OMERACT Filter 2.2 We systematically reviewed five databases (Ovid MEDLINE®, Embase, Cochrane Library, CINAHL and Web of Science). An information specialist designed search strategies to identify all measurement instruments used in SDM studies in adults or children living with rheumatic or musculoskeletal diseases or their important others. Paired reviewers independently screened titles, abstracts, and full text articles. We extracted characteristics of all candidate instruments (e.g., measured construct, measurement properties). We classified candidate instruments and summarized evidence gaps with an adapted version of the Summary of Measurement Properties (SOMP) table. RESULTS: We found 14,464 citations, read 239 full text articles, and included 99 eligible studies. We identified 220 potential candidate instruments. The five most used measurement instruments were the Decisional Conflict Scale (traditional and low literacy versions) (n=38), the Hip/Knee-Decision Quality Instrument (n=20), the Decision Regret Scale (n=9), the Preparation for Decision Making Scale (n=8), and the CollaboRATE (n=8). Only 44 candidate instruments (20%) had any measurement properties reported by the included studies. Of these instruments, only 57% matched with at least one of the 7-criteria adapted SOMP table. CONCLUSION: We identified 220 candidate instruments used in the SDM literature amongst people with rheumatic and musculoskeletal diseases. Our classification of instruments showed evidence gaps and inconsistent reporting of measurement properties. The next steps for the OMERACT SDM Working Group are to match candidate instruments with Core Domains, assess feasibility and review validation studies of measurement instruments in rheumatic diseases or other conditions. Development and validation of new instruments may be required for some Core Domains.

Patient outcomes in longitudinal observational studies (POLOS) of rheumatoid arthritis: Determining the OMERACT core domain set.

OBJECTIVE: To define and select rheumatoid arthritis (RA)-specific core domain set for Longitudinal Observational Studies (LOS) within the Outcome Measures in Rheumatology (OMERACT) framework. METHODS: A three-round online Delphi exercise, including patient research partners (PRPs) and other community partners in healthcare, was conducted. Domains scored 7-9 (i.e., critically important to include) by ≥ 70 % of participants in both groups were included. Items were consolidated in a subsequent dedicated meeting. RESULTS: Nineteen domains scored ≥ 70 % consensus in both groups. The focus group refined these into a list of twelve domains. CONCLUSION: The achieved consensus will inform the next steps of developing the core domain set for LOS in RA.

Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases.

Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35-3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95-5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.

Stakeholder endorsement advancing the implementation of a patient-reported domain for harms in rheumatology clinical trials: Outcome of the OMERACT Safety Working Group.

OBJECTIVES: To develop an understanding of the concept of safety/harms experienced by patients involved in clinical trials for their rheumatic and musculoskeletal diseases (RMDs) and to seek input from the OMERACT community before moving forward to developing or selecting an outcome measurement instrument. METHODS: OMERACT 2023 presented and discussed interview results from 34 patients indicating that up to 171 items might be important for patients' harm-reporting. RESULTS: Domain was defined in detail and supported by qualitative work. Participants in the Special-Interest-Group endorsed (96 %) that enough qualitative data are available to start Delphi survey(s). CONCLUSION: We present a definition of safety/harms that represents the patient voice (i.e., patients' perception of safety) evaluating the symptomatic treatment-related adverse events for people with RMDs enrolled in clinical trials.

Learning Needs of Patients with Cancer and a Pre-Existing Autoimmune Disease Who Are Candidates to Receive Immune Checkpoint Inhibitors.

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee's opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers.

Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events.

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs. METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment. RESULTS: We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04). CONCLUSION: Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).

Physician Views on the Provision of Information on Immune Checkpoint Inhibitor Therapy to Patients with Cancer and Pre-Existing Autoimmune Disease: A Qualitative Study.

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide information to patients and delivery options; (2) factors to make decisions about whether or not to start ICIs in patients who have cancer and pre-existing autoimmune conditions; (3) learning points for patients to understand; (4) preferences for the delivery of ICI information; and (5) barriers to the implementation of ICI information in clinics. Regarding points to discuss with patients, physicians agreed that the benefits of ICIs, the probability of irAEs, and risks of underlying autoimmune condition flares with the use of ICIs were most important. Non-oncologists were additionally concerned about how ICIs affect the autoimmune disease (e.g., impact on disease activity, need for changes in medications for the autoimmune disease, and monitoring of autoimmune conditions).