BackgroundImmune Checkpoint Inhibitors (ICI) have revolutionised the management of several cancers, enhancing the anti-tumoral immune response. However they are responsible for many Immune Related Adverse Effects (IRAE), and therefore most patients with Preexisting Autoimmune Diseases (PAD) have been excluded from clinical trials.ObjectivesThe aim of this study was to evaluate the safety and efficacy of ICI in patients with PAD.MethodsThree national expert networks, focusing respectively on skin cancers, thoracic cancers and inflammatory diseases participated in this study. All patients who received an ICI despite a PAD in clinical practice were included in this nationwide retrospective study.Results112 patients were included: 64 men (57.1%), median age 66.5. Most patients received an anti-PD1 or anti-PD-L1 drug (84.8%). Main cancer types were melanoma (n=66, 58.9%) and Non-Small Cell Lung Carcinoma (NSCLC) (n=40; 35.7%). Median follow-up was 8 months [0–52].Most frequent PAD were psoriasis and psoriatic arthritis (27.6%), rheumatoid arthritis (17.8%), inflammatory bowel disease (12.5%), spondyloarthritis (4.5%), lupus (6.3%), polymyalgia rheumatica and/or giant-cell arteritis (6.3%). 24 patients (21.6%) were receiving an immunosuppressive therapy (IS) at ICI initiation (including steroids in 15, sDMARD in 10 and rituximab in 1). 37 patients (33%) had an active disease.PAD flares were frequent (n=47; 42%) and 30.4% of them were severe (grade CTCAE 3–4). 26 patients (56.5%) received an IS treatment for a flare (22 received steroids and 7 a DMARD). Other IRAEs not related to the PAD occurred in 43 patients (38.4%), 41.5% were severe. 23 patients (56.1%) required an IS (including a DMARD in 4). 36 patients (32.1%) discontinued ICI temporarily or definitively because of a flare or an IRAE. One patient died due to an IRAE.Concerning the anti-tumoral response, the Overall Response Rate (ORR) was 48.3% for melanoma and 53.8% for NSCLC. The median Progression Free Survival (PFS) was 12.4 months for melanoma and 9.7 for NSCLC. Median overall survival (OS) was not reached in any group. PFS and OS were shorter in patients receiving an IS treatment at ICI initiation (p=0.007, figure 1A, and p=0.003, respectively). PFS and OS were longer in patients who experienced a PAD flare or other IRAE, but this gain was lost when an IS was used to treat the flare/IRAE (p=0.008, figure 1B, and p=0.01, respectively). Conversely, this gain was not impacted with ICI discontinuation.ConclusionsPAD flares and other IRAEs are frequent during ICI therapy and may be severe. The OS, ORR and PFS seem high in patients with PAD. The occurrence of a flare/IRAE is associated to a better outcome, gain lost when IS are used, while ICI discontinuation has no impact on PFS. Further prospective studies are needed to confirm our findings.Disclosure of InterestNone declared

Rheumatoid arthritis is a prevalent worldwide disease, associated with an increased risk of multiple metabolic abnormalities that generate a higher disease burden. Objective: To gather the available evidence on the epidemiology, pathophysiology, current perspectives, clinical implications and prognosis of metabolic abnormalities in patients with rheumatoid arthritis. Methods: This is a narrative literature review. Search was conducted in PubMed, OVID, and Taylor & Francis databases, using the following MeSH terms: "Arthritis Rheumatoid", "Metabolic Diseases", and "Metabolic Syndrome". Results: This study describes the main metabolic manifestations of rheumatoid arthritis. Research has recognized that rheumatoid arthritis and metabolic abnormalities share pathophysiological mechanisms with an additive effect that increases cardiovascular risk. In that context, appropriate antirheumatic treatment can also impact on cardiovascular risk. Conclusion: There are metabolic abnormalities in rheumatoid arthritis patients that increase cardiovascular risk. Therefore, it is crucial to evaluate cardiovascular risk to provide appropriate comprehensive management to reduce morbidity and mortality in patients with this disease.

Background: Novel combination therapies have been shown to improve the outcomes of treatment-naive patients with locally advanced or metastatic renal cell carcinoma (aRCC). However, the optimal systemic therapy for aRCC of favorable risk has yet to be clarified. We aimed to evaluate the efficacy and safety of different immunotherapy (IO) combinations, either with another IO (IO–IO) or with an antiangiogenic (IO–TKI), versus sunitinib in the first-line setting in aRCC patients with favorable IMDC risk. Methods: We conducted a systematic search for evidence in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials published up to February 2021. The GRADE approach was used to assess the quality of evidence. Survival hazard ratios were extracted for analysis in the favorable-risk aRCC subgroup (IMDC). A sensitivity analysis was performed excluding trials of combination therapy without TKI. Results: Five randomized controlled phase III trials with a total of 1088 patients were included in the analysis. The studies compared different combinations versus sunitinib monotherapy. All clinical trials reported overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) data. Four out of five trials reported complete response (CR). There was no difference in OS nor PFS between treatment arms in the IMDC favorable-risk subgroup analysis (OS: HR = 1.07, 95% CI = 0.81–1.41; PFS: HR = 0.74, 95% CI = 0.46–1.19). A benefit in ORR and CR was found for combination therapy vs. sunitinib (ORR: HR = 1.89, 95% CI = 1.29–2.76; CR: HR = 3.58, 95% CI = 2.04–6.28). In the sensitivity analysis, including only IO–TKI vs. sunitinib, no difference in OS was found; however, an advantage in PFS was observed (OS: HR = 0.99, 95%CI 0.69–1.43; PFS: HR = 0.60 (0.45–0.81). The safety profile reported is consistent with previous reports. We did not find differences in the incidence of any adverse event (AE) or of grade ≥3 AEs. Conclusion: This meta-analysis shows that combinations of IO–KI as first-line treatment in favorable-IMDC-risk aRCC improve PFS, ORR, and CR, but not OS, versus sunitinib.

Purpose To describe clinical characteristics and effectiveness of health care in patients with rheumatoid arthritis (RA) as part of a multidisciplinary care model (MCM) in a specialized rheumatology center, compared with the results of a national registry of RA (NARRA) as evidence of real-world management. Patients and Methods We conducted a real-world study (July 1, 2018 to June 30, 2019) based on an analysis of electronic health records of a cohort of RA patients managed with the “Treat-to-Target” strategy in a specialized rheumatology center in Colombia with an MCM, compared with the NARRA that includes different models of usual care. Results We have analyzed 7053 subjects with RA treated at a specialized rheumatology center and 81,492 patients from the NARRA. Cohorts were similar in their baseline characteristics, with women in predominance and diagnosis age close to 50 years. At the time of diagnosis, a higher proportion of clinical diagnostic test use and rheumatology consultation access was observed in the specialized rheumatology center than in the national registry (4–6 per year versus three or less). In addition, higher proportions of patients in remission and low disease activity were reported for the specialized rheumatology center, with a >40% amount of data lost in the national registry. Pharmacological management was similar regarding the analgesic use. In the specialized center, Certolizumab was more frequently used than in the NARRA registry; also, there were significant differences in methotrexate, leflunomide, and sulfasalazine use, being higher in the specialized rheumatology center. Conclusion The MCM of a specialized center in RA can guarantee comprehensive care, with better access to all the services required to manage the disease. It ensures specialist management and evidence-based care that facilitates the achievement of therapeutic objectives. In addition, better patient records and follow-ups are available to evaluate health outcomes.

Introduction: The antimalarials chloroquine and hydroxychloroquine have been used for several decades in treating malaria and some autoimmune diseases—mainly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)—with excellent efficacy and safety. Due to the massive use of antimalarials worldwide for managing SARS-CoV-2/COVID-19 infection during the last 2 years and the consequent increase in cardiac arrhythmia, fear has risen about the safety of using antimalarials, especially for patients with increased cardiovascular risk.Objective: To describe a real-life experience about the safety of antimalarials in the setting of a single rheumatological center in Colombia.Methods: This is a cross sectional study that includes patients diagnosed with RA and treated with antimalarials between 2020 and 2021. Clinical follow-up information was gathered from the medical records, and all reported adverse events were described.Results: A total of 957 patients were included, primarily women (79.2%). The most frequent comorbidities were hypertension and osteoporosis. Chloroquine use was more frequent than hydroxychloroquine (86.4% vs. 13.6%). During the observation period, 243 (25.4%) patients presented at least one adverse event, 72 (29.6%) had retinal toxicity, 85 (35%) dermatological events, and 81 (33.3%) gastrointestinal intolerance. Other adverse events reported less frequently (15.2%) included headache, dizziness, lipothymia, and elevated transaminases. There were no reports of cardiovascular events from the period of antimalarial use to the date of data collection despite the high frequency of previous metabolic or cardiovascular disease in this cohort.Conclusion: This study reasserts the evidence of antimalarials safety profile for patients with rheumatological conditions such as RA. RA patients that were treated with antimalarials at doses recommended by the guidelines had no cardiovascular events.

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Objective Although it is known that methotrexate (MTX) increases the effectiveness of biological drugs (mainly anti-TNFs) in patients with rheumatoid arthritis (RA), in real life, it is known that many patients using anti-TNFs are on monotherapy due to many causes. This article compares the effectiveness of certolizumab as monotherapy as combined with MTX or leflunomide (LFN) in RA patients with failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in a real-world setting. Methods A retrospective observational cohort study was conducted at a specialized centre for RA management in Colombia. Patients treated with certolizumab as monotherapy or in combination with MTX, LFN, or MTX+LFN, between 2011 and 2020 with a minimum 3-month follow-up were included. Demographics and RA clinical characteristics were recorded; effectiveness was assessed as the improvement in Disease Activity Score (DAS28) getting remission or low disease activity at 3, 6, and 12 months of treatment. Results A total of 181 patients were included, 24 received certolizumab as monotherapy, 62 certolizumab plus MTX, 47 certolizumab plus LFN and 48 certolizumab plus MTX+LFN. At 3 months of follow-up, 80% of the patients showed decreased disease activity, with no significant differences between groups; at 12 months of treatment, response in certolizumab monotherapy group was 94.4% compared to 81.8% in combination with MTX, 80.5% in combination with LFN and 51.4% in combination with MTX+LFN. Response at 3 months (OR 4.04; 95% CI 1.28–12.69) and positive anti-CCP (OR 3.83; 95% CI 1.11–13.21) were associated with 12-month response. Conclusion Certolizumab seems to be effective as monotherapy in the treatment of RA patients with failure to csDMARDs.

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