Elevated CK from immune checkpoint inhibitor- related hypophysitis: a case report.

Immune checkpoint inhibitors (ICIs), have emerged to the forefront of management for various advanced cancers, such as melanoma, lung cancer and renal cell carcinoma. Immune checkpoints such as CTLA-4 and PD-1 serve to inhibit T cell activation and signaling; therefore through blockade of these pathways, ICIs promote anti-tumour immune activation. However, as a result of T cell disinhibition, ICIs have been reported to cause immune related adverse events (irAEs) affecting numerous organ systems. One of the most serious and potentially life-threatening irAE is inflammatory myositis. Myositis, which generally presents with progressive proximal muscle weakness and elevated serum creatine kinase (CK), has been reported in <1% of patients who have received ICI therapy. A rare cause of elevated CK is adrenal insufficiency, which has been reported in up to 6% of ICI users. Here we report a case of ICI-related hypophysitis related myopathy that was initially misdiagnosed as ICI-associated inflammatory myositis. This case illustrates the importance of considering a wide differential when assessing hyperCKemia in the setting of ICI use.

False-positive Findings of Large Vessel Vasculitis on FDG-PET in Patients Treated With Immune Checkpoint Inhibitors.

Fluorine-18 fluorodeoxygluocose positron emission tomography (FDG-PET) is increasingly used in the evaluation of response to immune checkpoint inhibitor (ICI) therapy. Incidental findings of increased vessel wall uptake may prompt the concern for ICI-induced large vessel vasculitis (LVV). Precise radiographic and clinical evaluation is required to determine if this represents true vasculitis, as use of immune suppression and ICI discontinuation can have significant impacts on patient outcomes. We performed a retrospective case analysis of 4 consecutive patients referred to 2 rheumatology clinics treated with ICI with incidental findings of LVV on FDG-PET, reviewing their clinical course and radiographic findings. All 4 cases had FDG-PET scans for routine oncology indications and had no associated clinical features of LVV. One patient was treated with corticosteroids and no patients developed any clinical evidence of vasculitis during a mean follow-up period of 17 months (range: 7-33 mo). All FDG-PET images reporting LVV underwent a standardized analysis to identify any technical issues or concerns with interpretation. In review of imaging, 3 of the cases may have been due to delayed tracer to scan interval leading to misinterpretation of vascular uptake as suspected LVV. Recognition of technical pitfalls in FDG-PET interpretation is crucial to inform the need for immunosuppression and the safety of continued ICI therapy.

FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry.

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 ± 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk.

The Utility of Laboratory Investigations for the Assessment and Management of Rheumatic Immune Related Adverse Events.

Immune checkpoint inhibitors (ICIs) have greatly improved survival of several cancers with historically very poor prognosis. ICIs act by stimulating the patient's own immune system to fight cancer. Simultaneously, this immune activation can lead to immune-related adverse events (irAEs), including rheumatic manifestations (Rh-irAEs). Rh-irAEs mimic primary rheumatic diseases including arthritis, polymyalgia rheumatica, myositis, vasculitis, sarcoidosis, and sicca. This article summarizes the latest evidence regarding the utility of laboratory investigations in Rh-irAEs.

Immune Checkpoint Inhibitor-Associated Remitting Seronegative Symmetrical Synovitis With Pitting Edema: Description of a New Entity by CanRIO.

OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is characterized by symmetrical synovitis with pitting edema and negative rheumatoid factor (RF). It has been described in a setting of malignancy, suggesting a paraneoplastic association. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of cancers and emergence of immune-related adverse events (irAEs), our objective was to identify and describe cases of ICI-associated RS3PE (ICI-RS3PE) and compare them to non-ICI-RS3PE. METHODS: The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) network is a collaboration of Canadian rheumatologists with experience in the management of patients with rheumatic irAEs (Rh-irAEs). Standardized data on adult patients with Rh-irAE have been collected as part of retrospective and prospective cohorts. In this study, detailed information on all cases of ICI-RS3PE from both cohorts were extracted and analyzed. RESULTS: We identified 11 cases of ICI-RS3PE. The most frequently observed malignancy was nonsmall cell lung cancer (4 of 11), followed by malignant melanoma (2 of 11) and cutaneous squamous cell carcinoma (2 of 11). The median time to onset of ICI-RS3PE was 26 weeks from ICI start and 52 weeks from diagnosis of malignancy. Seven patients had stable cancer prior to onset of ICI-RS3PE, 3 had partial response, and 1 had complete response. All patients received glucocorticoids. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) were needed in 10 patients. CONCLUSION: ICI-RS3PE may be an independent Rh-irAE, separate from paraneoplastic RS3PE. The symptoms of ICI-RS3PE responded well to glucocorticoids, but concomitant treatment with csDMARDs may be necessary.

Targeted Coaching to Improve Osteoporosis Therapy Adherence: A Single Arm Variation of the C-STOP Study.

BACKGROUND: In this pre-planned variation of the Comparing Strategies Targeting Osteoporosis to Prevent Fractures After an Upper Extremity Fracture (C-STOP) trial, we investigated whether adherence-specific coaching by the case manager (CM) further improved the adherence and persistence rates compared to those seen in the C-STOP trial. METHODS: We conducted a prospective observational cohort study of community-dwelling adults 50 years or older who suffered an upper-extremity fracture and were not previously treated with osteoporosis medications, to assess whether a well-trained CM can partner with patients to improve adherence to and persistence with oral bisphosphonate intake. The primary outcome was adherence (taking > 80% of prescribed doses) to oral bisphosphonate intake at 12 months after study enrollment. Secondary outcomes included primary adherence to and 12-month persistence with oral bisphosphonate and calcium and vitamin D supplement intake at 12 months. RESULTS: The study cohort consisted of 84 participants, of which 30 were prescribed an oral bisphosphonate. Twenty-two (73.3%) started treatment within 3 months. The adherence rate at 12 months was 77.3%. The persistence rate at 12 months was 95.5%. Of those not prescribed an oral bisphosphonate, 62.8% were taking supplemental calcium and 93.0% were taking supplemental vitamin D at 12 months. Depression was a significant predictor of 12-month non-adherence (adjusted odds ratio, 9.8; 95% confidence interval, 1.2-81.5). CONCLUSIONS: Adherence-specific coaching by a CM did not further improve the level of medication adherence achieved in the original C-STOP study. Importantly, these results can inform adherence in future intervention studies.

Doctor Versus Artificial Intelligence: Patient and Physician Evaluation of Large Language Model Responses to Rheumatology Patient Questions in a Cross-Sectional Study.

OBJECTIVE: The objective of the current study was to assess the quality of large language model (LLM) chatbot versus physician-generated responses to patient-generated rheumatology questions. METHODS: We conducted a single-center cross-sectional survey of rheumatology patients (n = 17) in Edmonton, Alberta, Canada. Patients evaluated LLM chatbot versus physician-generated responses for comprehensiveness and readability, with four rheumatologists also evaluating accuracy by using a Likert scale from 1 to 10 (1 being poor, 10 being excellent). RESULTS: Patients rated no significant difference between artificial intelligence (AI) and physician-generated responses in comprehensiveness (mean 7.12 ± SD 0.99 vs 7.52 ± 1.16; P = 0.1962) or readability (7.90 ± 0.90 vs 7.80 ± 0.75; P = 0.5905). Rheumatologists rated AI responses significantly poorer than physician responses on comprehensiveness (AI 5.52 ± 2.13 vs physician 8.76 ± 1.07; P < 0.0001), readability (AI 7.85 ± 0.92 vs physician 8.75 ± 0.57; P = 0.0003), and accuracy (AI 6.48 ± 2.07 vs physician 9.08 ± 0.64; P < 0.0001). The proportion of preference to AI- versus physician-generated responses by patients and physicians was 0.45 ± 0.18 and 0.15 ± 0.08, respectively (P = 0.0106). After learning that one answer for each question was AI generated, patients were able to correctly identify AI-generated answers at a lower proportion compared to physicians (0.49 ± 0.26 vs 0.97 ± 0.04; P = 0.0183). The average word count of AI answers was 69.10 ± 25.35 words, as compared to 98.83 ± 34.58 words for physician-generated responses (P = 0.0008). CONCLUSION: Rheumatology patients rated AI-generated responses to patient questions similarly to physician-generated responses in terms of comprehensiveness, readability, and overall preference. However, rheumatologists rated AI responses significantly poorer than physician-generated responses, suggesting that LLM chatbot responses are inferior to physician responses, a difference that patients may not be aware of.

Effectiveness and Safety of Immune Checkpoint Inhibitors in Cancer Patients With Autoimmune Disease: A Retrospective Cohort Study.

Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, patients with pre-existing autoimmune diseases (PADs) have largely been excluded from clinical trials evaluating this drug class. This study evaluates the effectiveness and safety of ICI therapy in individuals with PAD in a real-world setting. A retrospective study of patients exposed to ICI therapy between 2012 and 2019 was conducted. Patients with PAD were identified and matched to an ICI-exposed group without PAD based on age, sex, and cancer type. Primary outcomes included toxicity, time to treatment failure, overall survival, and objective response rate. The association between PAD status and outcomes was determined using Cox and logistic regression modeling. A total of 813 patients exposed to ICI therapy were identified, of which 8.2% (N=67) had a PAD. When compared with a matched cohort without PAD (N=132), there was no significant difference in the rates of new immune-related adverse events (irAEs, 42.4% in the non-PAD group vs. 47.8% in the PAD group, P=0.474). After controlling for the type of ICI, there was no significant association between PAD status and irAE (odds ratio 1.67, 95% CI: 0.9-3.21 P=0.1). There was no significant association between overall survival and PAD status (hazard ratio 1.12, 95% CI: 0.76-1.66. P=0.56) or between time to treatment failure and PAD status (hazard ratio 0.82, 95% CI: 0.6-1.12, P=0.22). There was an association between PAD status and objective response rate (odds ratio 3.28, 95% CI: 1.28-8.38, P=0.013). In summary, PAD status was not associated with enhanced toxicity when compared with patients without PAD, with similar oncologic effectiveness between these 2 groups.

Adjusting FRAX Estimates of Fracture Probability Based on a Positive Vertebral Fracture Assessment.

Importance: FRAX is the most widely used and validated fracture risk prediction tool worldwide. Vertebral fractures, which are an indicator of subsequent osteoporotic fractures, can be identified using dual-energy x-ray absorptiometry (DXA) vertebral fracture assessment (VFA). Objective: To assess the calibration of FRAX and develop a simple method for improving FRAX-predicted fracture probability in the presence of VFA-identified fracture. Design, Setting, and Participants: This prognostic study analyzed the DXA and VFA results of all individuals who underwent a VFA between March 31, 2010, and March 31, 2018, who were included in the Manitoba Bone Mineral Density Registry. These individuals were randomly assigned to either the development cohort or validation cohort. A modified algorithm-based qualitative approach was used by expert readers to code VFAs as positive (≥1 vertebral fractures detected) or negative (0 vertebral fracture detected). Statistical analysis was conducted from August 7, 2022, to May 22, 2023. Exposures: FRAX scores for major osteoporotic fracture (MOF) and hip fracture were calculated with or without VFA results. Main Outcomes and Measures: Incident fractures and death were ascertained using linked population-based health care provincial data. Cumulative incidence curves for MOF and hip fracture were constructed, including competing mortality, to predict the 10-year observed risk of fracture. The observed probability was compared with FRAX-predicted fracture probability with and without VFA results and recalibrated FRAX from derived multipliers. Results: The full cohort of 11 766 individuals was randomly allocated to the development cohort (n = 7854; 7349 females [93.6%]; mean [SD] age, 75.7 [6.8] years) or the validation cohort (n = 3912; 3713 females [94.9%]; mean [SD] age, 75.5 [6.9] years). Over a mean (SD) observation time of 3.8 (2.3) years, with the longest observation at 7.5 years, FRAX was well calibrated in subgroups with negative VFA results. For individuals without a prior clinical fracture but with a positive VFA result, the 10-year FRAX-predicted MOF probability was 16.3% (95% CI, 15.7%-16.8%) without VFA information and 23.4% (95% CI, 22.7%-24.1%) with VFA information. The observed 10-year probabilities were 26.9% (95% CI, 26.0%-27.8%) and 11.2% (95% CI, 10.3%-12.1%), respectively, resulting in recalibration multipliers of 1.15 (95% CI, 0.87-1.43) for MOF and 1.31 (95% CI, 0.75-1.87) for hip fracture. For individuals with a prior clinical fracture and a positive VFA result, the 10-year FRAX-predicted probabilities were 25.0% (95% CI, 24.2%-25.7%) for MOF and 9.3% (95% CI, 8.7%-10.0%) for hip fracture. The observed 10-year probabilities were 38.1% (95% CI, 37.0%-39.1%) for MOF and 16.4% (95% CI, 15.4%-17.4%) for hip fracture, resulting in a recalibration multiplier of 1.53 (95% CI, 1.10-1.96) for MOF and 1.76 (95% CI, 1.17-2.35) for hip fracture. Good calibration (>0.90) was confirmed using the derived multipliers in the validation cohort. Conclusions and Relevance: Results of this prognostic study suggest that FRAX underestimated fracture risk in patients with VFA-identified fractures. Simple multipliers could recover FRAX calibration in individuals with VFA-identified fractures.

Biological Sex Inequality in Rheumatology Wait Times During the COVID-19 Pandemic.

OBJECTIVE: To examine the effect of biological sex on wait times to first rheumatology appointment in a central triage system before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Deidentified data of all referred patients between November 2019 and June 2022 were extracted from the electronic medical record. Variables, including time from referral to first appointment, biological sex, referral period, urgency status, age, and geographic location were collected and analyzed. RESULTS: Twelve thousand eight hundred seventeen referrals were identified. Wait times increased by 24.23 days in the peri-COVID period (P < 0.001). In the pre-COVID period, there was no significant difference in wait times by biological sex or age. Triage urgency was a predictor of wait time, with semiurgent referrals seen 8.94 days (95% CI -15.90 to -1.99) sooner than routine referrals and urgent referrals seen 25.42 days (95% CI -50.36 to -0.47) sooner than routine referrals. In the peri-COVID period, there was a significant difference in wait time by biological sex with women waiting on average 10.03 days (95% CI 6.98-13.09) longer than men (P < 0.001). Older patients had shorter wait times than younger patients, with a difference of -4.64 days for every 10-year increase in age (95% CI -5.49 to -3.78). Triage urgency continued to be a predictor of wait time. CONCLUSION: Women and younger patients appear to have been affected by wait time increases during the COVID-19 pandemic. This finding should be further investigated to determine its pervasiveness across other specialities and to better understand the underlying cause of this finding.

Performance of FRAX in Men With Prostate Cancer: A Registry-Based Cohort Study.

The Fracture Risk Assessment Tool (FRAX®) was created to predict major osteoporotic fractures (MOF) and hip fractures in the general population. Whether FRAX accurately predicts fractures in men with prostate cancer is unknown. Our objective was to assess the performance of FRAX for predicting incident fractures in men with prostate cancer. Men from the Manitoba Bone Mineral Density (BMD) Registry (1996-2018) with prostate cancer diagnoses in the 3 years prior to dual-energy X-ray absorptiometry (DXA) were identified. FRAX scores with and without BMD were calculated. From population-based healthcare data we identified incident MOF, hip fracture, any osteoporotic fracture and death from the date of BMD testing to March 31, 2018. Cox regression was performed to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) per standard deviation increase in FRAX score. Observed 10-year probability (estimated with competing risk of mortality) was compared with 10-year FRAX-predicted fracture probability to assess calibration. The study population included 684 men with prostate cancer (mean age 74.6 years) and 8608 men without prostate cancer (mean age 65.5 years). FRAX stratified risk for MOF (HR 1.91, 95% CI 1.48-2.45 with BMD; HR 1.96, 95% CI 1.43-2.69 without BMD) and hip fracture (HR 3.37, 95% CI 1.90-6.01 with BMD; HR 4.58, 95% CI 2.17-9.67 without BMD) in men with prostate cancer. There was no effect modification observed with prostate cancer status or current androgen deprivation therapy. Observed 10-year fracture probability in men with prostate cancer showed good agreement with FRAX with and without BMD included in the calculation (observed/predicted calibration ratios MOF 0.97, hip 1.00 with BMD; MOF 0.92, hip 0.93 with BMD). In conclusion, FRAX reliably predicts incident fractures in men with prostate cancer. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Fracture rate increases after immune checkpoint inhibitor treatment: a potential new immune related adverse event.

INTRODUCTION: T cell activation can lead to osteoporosis and while there are several case reports of fractures occurring after immune checkpoint inhibitor (ICI) use, to date, there are no population level studies looking at fracture risk related to ICI use. METHODS: Using Alberta Cancer Registry data, we identified all individuals treated with ICI for cancer between September 29, 2010, and March 31, 2019. Linked records from Alberta's healthcare administrative databases were assessed for the presence of fracture diagnostic codes in the year prior to and up to two years after ICI initiation. Fracture rate was stratified based on the time-period before and after ICI initiation. Fracture rates after ICI were compared to baseline. RESULTS: The study cohort consisted of 1600 ICI users (mean age 65.7 years, 60% male). Most patients were treated with an anti-PD-1 agent (73.9%). ICIs were initiated on average 707.8 days after cancer diagnosis. 76 (4.8%) individuals had a remote history of a major fracture, and 141 (8.8%) had been treated with an osteoporosis medication prior to ICI treatment. The fracture rate in the year prior to ICI initiation was 11.3 per 1000 patient-years. The fracture rate in the year after ICI initiation was significantly higher at 27.3 per 1000 patient-years. The fracture rate dropped to 17.6 per 1000 patient-years in the second year after ICI initiation. The incidence rate ratio of sustaining a major fracture in the year after compared to the year prior to ICI initiation was 2.43 (95% CI 1.34-4.27). CONCLUSIONS: Fracture risk may be increased in cancer patients early after initiation of ICI, and this may represent a novel immune-related adverse event.

Fracture risk and assessment in adults with cancer.

Individuals with cancer face unique risk factors for osteoporosis and fractures. Clinicians must consider the additive effects of cancer-specific factors, including treatment-induced bone loss, and premorbid fracture risk, utilizing FRAX score and bone mineral densitometry when available. Pharmacologic therapy should be offered as per cancer-specific guidelines, when available, or local general osteoporosis guidelines informed by clinical judgment and patient preferences. Our objective was to review and summarize the epidemiologic burden of osteoporotic fracture risk and fracture risk assessment in adults with cancer, and recommended treatment thresholds for cancer treatment-induced bone loss, with specific focus on breast, prostate, thyroid, gynecological, multiple myeloma, and hematopoietic stem cell transplant. This narrative review was informed by PubMed searches to July 25, 2022, that combined terms for cancer, stem cell transplantation, fracture, bone mineral density (BMD), trabecular bone score, FRAX, Garvan nomogram or fracture risk calculator, QFracture, prediction, and risk factors. The literature informs that cancer can impact bone health in numerous ways, leading to both systemic and localized decreases in BMD. Many cancer treatments can have detrimental effects on bone health. In particular, hormone deprivation therapies for hormone-responsive cancers such as breast cancer and prostate cancer, and hematopoietic stem cell transplant for hematologic malignancies, adversely affect bone turnover, resulting in osteoporosis and fractures. Surgical treatments such as hysterectomy with bilateral salpingo-oophorectomy for gynecological cancers can also lead to deleterious effects on bone health. Radiation therapy is well documented to cause localized bone loss and fractures. Few studies have validated the use of fracture risk prediction tools in the cancer population. Guidelines on cancer-specific treatment thresholds are limited, and major knowledge gaps still exist in fracture risk and fracture risk assessment in patients with cancer. Despite the limitations of current knowledge on fracture risk assessment and treatment thresholds in patients with cancer, clinicians must consider the additive effects of bone damaging factors to which these patients are exposed and their premorbid fracture risk profile. Pharmacologic treatment should be offered as per cancer-specific guidelines when available, or per local general osteoporosis guidelines, in accordance with clinical judgment and patient preferences.

Fractures and long-term mortality in cancer patients: a population-based cohort study.

We assessed post-fracture mortality in a population-based cohort of 122,045 individuals with cancers. Major fractures (hip, vertebrae, humerus, and forearm) were associated with early and long-term increased all-cause mortality. INTRODUCTION: Currently, there are no population-based data among cancer patients on post-fracture mortality risk across a broad range of cancer diagnoses. Our objective was to estimate the association of fracture with mortality in cancer survivors. METHODS: Using Manitoba Cancer Registry data from the province of Manitoba, Canada, we identified all women and men with cancer diagnosed between January 1, 1987, and March 31, 2014. We then linked cancer data to provincial healthcare administrative data and ascertained fractures after cancer diagnosis and mortality to March 31, 2015. Hazard ratios for all-cause mortality in those with versus without fracture were estimated from time-dependent Cox proportional hazards models adjusted for multiple covariates. RESULTS: The study cohort consisted of 122,045 cancer patients (median age 68 years, IQR 58-77, 49.2% female). During the median follow-up of 5.8 years from cancer diagnosis, we ascertained 7120 (5.8%) major fractures. All fracture sites, except for the forearm, were associated with increased mortality risk, even after multivariable adjustment. Excess mortality risk associated with a major fracture was greatest in the first year after fracture (HR 2.42, 95% CI 2.30-2.54) and remained significant > 5 years after fracture (HR 1.60, 95% CI 1.50-1.70) and for fractures occurring > 10 years after cancer diagnosis (HR 1.93, 95% CI 1.79-2.07). CONCLUSION: Fractures among cancer patients are associated with increased all-cause mortality. This excess risk is greatest in the first year and persists more than 5 years post-fracture; increased risk is also noted for fractures occurring up to and beyond 10 years after cancer diagnosis.

Rapid Unmasking of Immune-related Adverse Events After Discontinuation of Chemotherapy in Chemo-immunotherapy Regimens.

Pembrolizumab is an immune-checkpoint inhibitor (ICI) of programmed cell death protein 1 (PD-1), which restores T-cell-mediated antitumor immune activity and therefore enhances the body's immune response to cancer cells. Due to the nature of this therapy, immune-related adverse events (irAE) can manifest in nearly every organ system. Chemo-immunotherapy regimens are now considered first-line treatment for several cancers, with recent literature suggesting there are higher rates of certain irAEs with ICI monotherapy when compared with chemo-immunotherapy combinations. In certain regimens chemo-immunotherapy induction is followed by ICI maintenance monotherapy, and data regarding irAE incidence in this transition period are very limited. We report 3 cases of patients on pembrolizumab in combination with cytotoxic chemotherapy who developed an irAE shortly following discontinuation of a chemotherapy agent. Cases were identified in the Rheumatology in Immuno-Oncology clinic at the University of Alberta and clinical data were extracted by retrospective chart review after obtaining written consent from individual patients. These findings demonstrate that chemotherapy may suppress irAEs in patients using ICIs, and that when chemotherapy agents in combined regimens are discontinued, irAEs can be "unmasked" within the following 6 weeks. Clinicians should be aware of this risk and monitor for irAE development during this critical time period. To the best of the authors' knowledge, this has not been previously reported in the literature.

Evaluation of care delivery by a novel multidisciplinary bone health clinic for patients at risk of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis (GIOP) is a common condition associated with increased risk for fracture. Many patients receive suboptimal care. We created a novel GIOP clinic model which successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population. INTRODUCTION: This study characterizes the patient population referred to our novel glucocorticoid-induced osteoporosis (GIOP) clinic and evaluates how well the clinic performed in addressing key components of GIOP preventive care. METHODS: This population-based prospective cohort study derives data from patients reviewed at the University of Alberta Multidisciplinary Bone Health Clinic from January 2017 to September 2019. To create our clinic model, key components of GIOP preventive care were summarized based on current guidelines, and clear responsibilities were delegated to each multidisciplinary team member. A REDCap database was constructed, and each patient's multidisciplinary assessment was entered at each visit. Demographic and treatment data was extracted from our database. RESULTS: The clinic was able to achieve optimal GIOP preventive care in 60.1% of patients and in 78.7% of patients when excluding wait time. Of the 245 GIOP patients assessed, over half were females (56.7%) and the mean age was 56.7 years (range 16-95 years). Referrals were primarily made by specialists. Low-trauma fractures were reported in 24.9% of patients and 95.5% of patients had a baseline dual-energy X-ray absorptiometry (DXA). The mean current daily prednisone-equivalent dose was 14.1 mg. All patients received a recommendation for pharmacotherapy (100%) and the majority received counseling on vitamin D (98.8%), calcium (97.8%), smoking cessation (98.8%), alcohol reduction (98.4%), falls prevention (88.6%), and exercise (85.3%). CONCLUSION: Our novel GIOP clinic model successfully fills a gap in osteoporosis care by providing multidisciplinary intervention in key components of GIOP preventive care to an underserved patient population. Further studies are required to assess the real-world long-term outcomes of our model.