The Effects of Glucocorticoids and Immunosuppressants on Cancer Outcomes in Checkpoint Inhibitor Therapy

The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, abatacept, rituximab, and Janus kinase inhibitors (JAKi) on cancer-specific outcomes in the setting of immune checkpoint inhibitor use

Osteoarthritis: Patient Expectations about Future Pain, Stiffness and Function

Objectives The aim of the present study was to examine the difference between osteoarthritis patients’ self-reported assessments of current pain, stiffness and physical function and their expectations of these symptoms in one and five years’ time, and to determine the significant predictors of positive expectations. Methods Eighty patients completed ratings of baseline assessments and one- and five-year expectations of pain, stiffness and physical function using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Measures of illness perceptions, coping styles, health values, satisfaction, quality of life, optimism, self-esteem and moods were also collected at baseline. Agreement between patients’ current assessment and expectations were calculated using intra-class correlations (ICCs). Paired-sample t-tests were conducted to look at differences between assessments. Univariate logistic regressions were then performed to identify the variables significantly associated with positive expectations of pain, stiffness and function. Significant variables (p < 0.05) were entered into a forward stepwise multivariate logistic regression to identify unique independent predictors of positive expectations for each of the WOMAC subscales. Results Differences were found between current assessments and expectations, with the majority of patients being positive about future symptoms. There were some differences between the predictors for one- and five-year expectations, with current assessments of health status only affecting five-year expectations. Conclusions It is necessary to investigate further the variables that may contribute to positive expectations in osteoarthritis patients in order to manage the condition more effectively

Satisfactory cross cultural equivalence of the Dutch WOMAC in patients with hip osteoarthritis waiting for arthroplasty

Background: Cross cultural validity is of vital importance for international comparisons. Objective: To investigate the validity of international Dutch-English comparisons when using the Dutch translation of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Patients and Methods: The dimensionality, reliability, construct validity, and cross cultural equivalence of the Dutch WOMAC in Dutch and Canadian patients waiting for primary total hip arthroplasty was investigated. Unidimensionality and cross cultural equivalence was quantified by principal component and Rasch analysis. Intratest reliability was quantified with Cronbach's α, and test-retest reliability with the intraclass correlation coefficient. Construct validity was quantified by correlating sum scores of the Dutch WOMAC, Arthritis Impact Measurement Scales (Dutch AIMS2), Health Assessment Questionnaire (Dutch HAQ), and Harris Hip Score (Dutch HHS). Results: The WOMAC was completed by 180 Dutch and 244 English speaking Canadian patients. Unidimensionality of the Dutch WOMAC was confirmed by principal component and Rasch analysis (good fit for 20/22 items). The intratest reliability of the Dutch WOMAC for pain and physical functioning was 0.88 and 0.96, whereas the test-retest reliability was 0.77 and 0.92, respectively. Dutch WOMAC pain sum score correlated 0.69 with Dutch HAQ pain, and 0.39 with Dutch HHS pain. Dutch WOMAC physical functioning sum score correlated 0.46 with Dutch AIMS2 mobility, 0.62 with Dutch AIMS2 walking and bending, 0.67 with Dutch HAQ disability, and 0.49 with Dutch HHS function. Differential item functioning (DIF) was shown for 6/22 Dutch items. Conclusions: The Dutch WOMAC permits valid international Dutch-English comparisons after correction for DIF

Health Advice from Internet Discussion Forums: How Bad Is Dangerous?

Background: Concerns over online health information–seeking behavior point to the potential harm incorrect, incomplete, or biased information may cause. However, systematic reviews of health information have found few examples of documented harm that can be directly attributed to poor quality information found online. Objective: The aim of this study was to improve our understanding of the quality and quality characteristics of information found in online discussion forum websites so that their likely value as a peer-to-peer health information–sharing platform could be assessed. Methods: A total of 25 health discussion threads were selected across 3 websites (Reddit, Mumsnet, and Patient) covering 3 health conditions (human immunodeficiency virus [HIV], diabetes, and chickenpox). Assessors were asked to rate information found in the discussion threads according to 5 criteria: accuracy, completeness, how sensible the replies were, how they thought the questioner would act, and how useful they thought the questioner would find the replies. Results: In all, 78 fully completed assessments were returned by 17 individuals (8 were qualified medical doctors, 9 were not). When the ratings awarded in the assessments were analyzed, 25 of the assessments placed the discussion threads in the highest possible score band rating them between 5 and 10 overall, 38 rated them between 11 and 15, 12 rated them between 16 and 20, and 3 placed the discussion thread they assessed in the lowest rating band (21-25). This suggests that health threads on Internet discussion forum websites are more likely than not (by a factor of 4:1) to contain information of high or reasonably high quality. Extremely poor information is rare; the lowest available assessment rating was awarded only 11 times out of a possible 353, whereas the highest was awarded 54 times. Only 3 of 78 fully completed assessments rated a discussion thread in the lowest possible overall band of 21 to 25, whereas 25 of 78 rated it in the highest of 5 to 10. Quality assessments differed depending on the health condition (chickenpox appeared 17 times in the 20 lowest-rated threads, HIV twice, and diabetes once). Although assessors tended to agree on which discussion threads contained good quality information, what constituted poor quality information appeared to be more subjective. Conclusions: Most of the information assessed in this study was considered by qualified medical doctors and nonmedically qualified respondents to be of reasonably good quality. Although a small amount of information was assessed as poor, not all respondents agreed that the original questioner would have been led to act inappropriately based on the information presented. This suggests that discussion forum websites may be a useful platform through which people can ask health-related questions and receive answers of acceptable quality

Expert Clinical Management of Inflammatory Immune-Related Arthritis in Patients with Cancer Receiving Immune Checkpoint Inhibitors

Immune checkpoint inhibitor therapy; Inflammatory arthritis; SurveyTeràpia amb inhibidors del punt de control immunitari; Artritis inflamatòria; EnquestaTerapia con inhibidores del punto de control inmunitario; Artritis inflamatoria; EncuestaIntroduction Treatment guidelines for immune-related inflammatory arthritis (irAE-IA) in patients with cancer receiving immune checkpoint inhibitors (ICIs) are vague with respect to the use of specific agents. Patients are usually referred to rheumatologists for treatment. We conducted a survey of expert rheumatologists to determine current practices. We also assessed experts’ views on the potential deleterious effects of various agents on tumor progression. Methods We conducted a survey of international experts in the treatment of irAE-IA, identified as members of collaborative scientific workgroups in this area. Experts were presented with a case of a patient with moderate irAE-IA and were asked about their preferred management including glucocorticoids, timing and initial choice of disease-modifying antirheumatic drugs (DMARDs), and perception of the deleterious effects of different agents on tumor progression. Results We approached 25 experts, of whom 19 (76%) responded. Most experts (63%) agreed on 20 mg or less of prednisone as initial dose. Experts selected methotrexate (41%) or tumor necrosis factor inhibitor (TNFi) (23%) as the initial DMARD if there was no improvement with corticosteroids; most experts (42%) would initiate DMARDs after 4 weeks. For patients whose initial DMARD therapy failed, the second choice was either a tumor necrosis factor inhibitor (TNFi) (38%) or interleukin-6 receptor antagonist (IL6ri) (33%). Experts were most concerned about the potential deleterious effects on tumor progression of abatacept and prednisone at doses of 20 mg or higher. Conclusion There was substantial heterogeneity in the initial management of irAE-IA. Further understanding of the pathophysiology of this immunotoxicity can assist in the classification of different presentations, selection of relevant outcomes, and planning of clinical trials to establish optimal therapeutic efficacy while minimizing potential deleterious effects of treatment on immune tumor responses

Defining the optimal biological monotherapy in rheumatoid arthritis: a systematic review and meta-analysis of randomised trials

Objectives To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. Methods We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800. Results The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included “DMARD-naïve”, and 20 “DMARD-Inadequate responder” (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068). Conclusions Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice

Individualized decision aid for diverse women with lupus nephritis (IDEA-WON): A randomized controlled trial.

BackgroundTreatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis.Methods and findingsIn a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of &lt;$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p &lt; 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence.ConclusionsAn individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis.Trial registrationClinicaltrials.gov, NCT02319525

Editorial: Multidisciplinary management of cancer patients with immune-related adverse events from checkpoint inhibitors

Cancer; Immunotherapy; ToxicityCáncer; Inmunoterapia; ToxicidadCàncer; Immunoteràpia; Toxicita

Telemedicine for Patients With Systemic Lupus Erythematosus in a Publicly Funded Hospital System: Retrospective Study

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that requires frequent clinic and laboratory visits. However, patients with SLE, particularly those who are underresourced, have unacceptably high rates of no-shows. OBJECTIVE: This study aims to determine no-show rates associated with telemedicine visits during the COVID-19 pandemic in comparison to no-show rates associated with contemporaneous and historic in-person visits. METHODS: We performed a retrospective cohort study in a publicly funded county hospital system in Houston, Texas. We identified a cohort of established patients with SLE by the International Classification of Diseases codes that were independently confirmed as SLE by a review of medical records. We identified patients who were seen from March to December in 2018, 2019, and 2020 (to reflect the height of the COVID-19 pandemic and account for seasonal changes in disease activity). Our primary outcome was the percentage of no-shows for rheumatology clinic appointments. Our secondary outcome was laboratory use adherence, which was defined as lupus-specific blood and urine studies conducted within 30 days of the scheduled appointment. Covariates included age, sex, race, ethnicity, and SLE-related prescription drugs. RESULTS: We included 156 patients with SLE in our analysis. Most were female (n=141, 90.4%), were Hispanic (n=75, 49.3%), and had a median age of 43 (range 19-80) years. In 2020, the no-show rate for telemedicine was 5.5% (10/182) compared to a no-show rate of 16.2% (31/191) for in-person visits (P=.002). After multivariable adjustment for covariates, the odds of no-show were lower for telemedicine visits (odds ratio 0.39, 95% CI 0.20-0.77). There were no differences in adherence to laboratory testing. CONCLUSIONS: Telemedicine visits had decreased odds of no-shows without difference in laboratory testing adherence after adjustment for covariates. More research is needed to determine the clinical impact of telemedicine on patients with SLE