ABSTRACT
BackgroundConsideration is needed when using Janus kinase (JAK) inhibitors to treat RA in pts aged ≥65 years or those with cardiovascular (CV) risk factors. The JAK1 preferential inhibitor FIL was generally well tolerated in clinical trials[1];safety has not been determined in a real-world setting.ObjectivesTo report baseline characteristics and up to 6-month safety data from the first 480 pts treated with FIL in the FILOSOPHY study (NCT04871919), and in two mutually exclusive subgroups based on age and CV risk.MethodsFILOSOPHY is an ongoing, phase 4, non-interventional, European study of pts with RA who have been prescribed FIL for the first time and in accordance with the product label in daily practice. Baseline characteristics and the incidence of select adverse events (AEs) are assessed in pts aged ≥65 years and/or with ≥1 CV risk factor (Table 1), and in those aged <65 years with no CV risk factors.ResultsAs of the end of June 2022, 480 pts had been treated: 441 received FIL 200 mg and 39 received FIL 100 mg. Of the 480 pts, 148 (30.8%) were aged ≥65 years;332 (69.2%) were aged <65 years. In total, 86 (17.9%) were former smokers, 81 (16.9%) were current smokers and 203 (42.3%) were non-smokers (data were missing for 110 pts [22.9%]). In addition to smoking, the most frequent CV risk factors included a history of hypertension (32.3%), a history of dyslipidemia (10.2%) and a family history of myocardial infarction (8.5%;Table 1).23 pts (4.8%) discontinued treatment due to AEs. Of the 354 pts aged ≥65 years or with ≥1 CV risk factor, infections affected 64 pts (18.1%), 34 (9.6%) had COVID-19, 2 (0.6%) had herpes zoster, and cardiac disorders (angina pectoris, atrial fibrillation, palpitations and tachycardia) affected 5 pts (1.4%);no cases of malignancies were observed. In the subgroup aged <65 years and with no CV risk factors (n=126), infections occurred in 18 pts (14.3%) (9 [7.1%] had COVID-19;3 [2.4%] had herpes zoster) and malignancies (myeloproliferative neoplasm) affected 1 pt (0.8%);no pts had cardiac disorders. There were no cases of deep vein thrombosis or pulmonary embolism in either subgroup.ConclusionIn this interim analysis of FILOSOPHY, no unexpected safety signals emerged at up to 6 months. Although infections and cardiac disorders affected a numerically greater proportion of pts aged ≥65 years or with ≥1 CV risk vs those aged <65 years with no CV risk, longer follow-up on a broader cohort is necessary to further characterize the safety of FIL in different groups of pts with RA.Reference[1]Winthrop K, et al. Ann Rheum Dis 2022;81:184–92Table 1.Baseline characteristics and CV risk factorsBaseline demographics/CV risk factorsAll FIL-treated pts (N=480)≥65 years or with ≥1 CV risk factor (n=354)<65 years and no CV risk factor (n=126)*Female sex, n (%)351 (73.1)252 (71.2)99 (78.6)Age, years, mean (SD)57.6 (11.5)60.4 (10.8)49.6 (9.6)Rheumatoid factor positive, n (%)†228 (47.5)167 (47.2)61 (48.4)Anti-citrullinated protein antibody positive, n (%)‡243 (50.6)176 (49.7)67 (53. 2)Body mass index, kg/m2, mean (SD)27.6 (5.7) n=43728.0 (5.4) n=33126.3 (6.4) n=106RA disease duration, years, mean (SD)10.4 (9.4) n=47810.5 (9.5) n=35310.0 (8.8) n=125Tender joint count 28, mean (SD)8.6 (6.9) n=4578.7 (7.1) n=3408.3 (6.3) n=117Swollen joint count 28, mean (SD)5.6 (5.2) n=4525.7 (5.4) n=3365.4 (4.4) n=116Former smoker, n (%)§86 (17.9)86 (24.3)0Current smoker, n (%)§81 (16.9)81 (22.9)0Non-smoker, n (%)§203 (42.3)130 (36.7)73 (57.9)Family history of myocardial infarction, n (%)41 (8.5)41 (11.6)0Medical history of: n (%) CV disease33 (6.9)33 (9.3)0 Diabetes35 (7.3)35 (9.9)0 Dyslipidemia49 (10.2)49 (13.8)0 Hypertension155 (32.3)155 (43.8)0 Ischemic CNS vascular disorders11 (2.3)11 (3.1)0 Peripheral vascular disease17 (3.5)17 (4.8)0*Includes 53 pts with missing smoking status data who were aged <65 years with no other CV risk factors.†Missing/unknown in 154 pts;‡Missing in 153 pts;§Smoking status data missing in 110 pts (22.9%).AcknowledgementsWe thank the physicia s and patients who participated in this study. The study was funded by Galapagos NV, Mechelen, Belgium. Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Verschueren Speakers bureau: AbbVie, Eli Lilly, Galapagos, Roularta, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Sidekick Health, Grant/research support from: Galapagos, Pfizer, Jérôme Avouac Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sandoz, Sanofi, Consultant of: AbbVie, Fresenius Kabi, Galapagos, Sanofi, Grant/research support from: BMS, Fresenius Kabi, Novartis, Pfizer, Karen Bevers Grant/research support from: Galapagos, Susana Romero-Yuste Speakers bureau: AbbVie, Biogen, BMS, Lilly, Pfizer, Consultant of: Sanofi, Lilly, Grant/research support from: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Thomas Debray Consultant of: Biogen, Galapagos, Gilead, Francesco De Leonardis Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer, Sanofi, Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer, Sanofi.
ABSTRACT
Background: Targeted Immune-Modulating Therapies (TIMT) and immunomodulators (IMM) for Immune Mediated Inflammatory diseases (IMID) theoretically interfere with humoral responses against COVID19. However, IMID patients and particularly patients receiving immunosuppressive treatment were excluded from phase-3 COVID19 vaccination efficacy trials. Real-world observational data is therefore required to provide more insight into the efficacy of COVID19 vaccination in IMID patients. Method(s): The BELCOMID study is a multidisciplinary, prospective observational cohort study performed at two university hospitals and set up with the intention to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Consecutive patients seen between 17/12/2020 and 28/02/2021 during routine follow-up for IMIDs of the gut, joints and skin were invited to participate. Both patient data and serological samples were collected at 3 predefined periods (Figure 1: Before vaccination, after start of the national vaccination campaign before booster vaccination, after booster vaccination). Spike (S) protein antibodies were analysed with the Abbott ArchitectTM assay. R version 4.0.2 was used to perform analyses. Result(s): At inclusion period 2, 2065 patients (Table 1) participated of whom 1547 had received complete baseline vaccination (2 doses mRNA-1273, BNT162b2, ChadOx1 nCoV-19 or 1 dose JN78436735). S-antibody seroconversion rate was 91.2%. At inclusion period 3, data was available for 1566 patients of whom 74.7% had received 1 booster (BNT162b2 or mRNA-1273) vaccination leading to a S-antibody seroconversion rate of 98.3%. In 130 patients who had received 2 boosters, S-antibody seroconversion rate was 100%. At period 3, 37 patients had refused all vaccinations. Although 23 of these had experienced confirmed COVID19 since previous inquiry, no S-antibody seroconversion was found in 15 of them. Logistic regression analyses revealed that the odds of no S-antibody seroconversion were significantly higher in IMID patients treated with IMM, combination of IMM+TIMT, systemic steroids and smoking patients at both inclusion periods (Table 2). TIMT monotherapy did not influence seroconversion rates at inclusion period 3 but was associated with higher odds of the lowest S-antibody titre quartile (OR2.32, P<0.001). Among TIMT options, rituximab had higher odds of S-seronegativity. Conclusion(s): S-antibody seroconversion rate in this real-life IMID population was high after baseline vaccination and increased further proportionally with booster vaccination, highlighting the value of repeated vaccination. However, the serologic response may be blunted due to different IMID treatment modalities and smoking.
ABSTRACT
Background: Patients with immune-mediated infammatory diseases (IMID) are at higher risk for infectious diseases. Despite this increased risk and the available guidelines1,2, we reported a suboptimal vaccination rate of 27 % of IMID patients in 2018. In the meantime, a vaccination module was introduced in the electronic patient medical record (EMR) of our hospital to accurately document and monitor vaccination status of patients. Objectives: To evaluate the impact of a new vaccination module in the patient health record on vaccination coverage in a previously included IMID cohort. Methods: Between Aug and Oct 2021, the vaccination status of 1435 (out of the original 1488) IMID patients (45 % male, median age 53.6 years) was collected (790 patients with IBD (infammatory bowel diseases), 607 with rheumatologic infammatory conditions (RHEU)(RA or SpA), and 38 with dermatologic infam-matory conditions(DER)) and was compared to that of 2018. The vaccination status for infuenza (FLU), pneumococci (Pnc), hepatitis B (Hep B) and tetanus (TT) was obtained mainly through the patients' electronic medical records. Missing data were added after contacting patients or their general practitioner. Results: From 2018 to 2021, the overall vaccination coverage (excluding TT) of all IMID patients signifcantly increased from 42 % to 66 % (p<0.001, Figure 1). For patients with RHEU, the vaccination coverage signifcantly increased, namely from 69.0% to 75 % for FLU (p<0.001), from 36 % to 89 % for Pnc (p<0.001), from 57 % to 73 % for Hep B (p<0.001) and from 34 % to 74 % overall (p=0.008) (Figure 1 and Table 1). Similarly, the vaccination coverage in IBD patients increased signifcantly from 76 % to 87 % for FLU (p<0.001), from 73 % to 82 % for Pnc (p<0.001), from 67 % to 79 % for Hep B (p<0.001) and from 47 % to 61 % overall (p<0.001) (Figure 1 and Table 1). For patients with DER, vaccination coverage signifcantly increased from 47 % to 65 % for Hep B (p<0.001) (Table 1). TT vaccination coverage decreased in all 3 IMID groups from 2018 to 2021. Conclusion: The implementation of a vaccination tool integrated in the EMR coincided with a signifcant increase in vaccination rates and also in the total amount of IMID patients that were fully vaccinated according to guidelines. Quite likely, the suboptimal vaccination rate measured in 2018 and the COVID-19 pandemic also raised awareness among patients and healthcare professionals about the importance of following vaccination guidelines.
ABSTRACT
Background Patients with immune-mediated inflammatory diseases (IMID) are at higher risk for infectious diseases. Despite this increased risk and the available guidelines1, we reported a suboptimal vaccination rate of 33.8% of IMID patients in 2018. In the meantime, a vaccination module was introduced in the electronic patient health record of our hospital to accurately document and monitor vaccination status of patients. The impact of this new module on vaccination coverage was re-evaluated in the same IMID patients in 2021. Methods Between Aug and Oct 2021, the vaccination status of 1448 (out of the original 1488) IMID patients (44.8% male, median age 53.6 years) was collected (798 patients with IBD, 612 with rheumatological, and 38 with dermatological inflammatory conditions) and compared to that of 2018. The vaccination status was obtained mainly through the patients' electronic medical records. Missing data were added after contacting patients or their general practitioner. Results From 2018 to 2021, the overall vaccination coverage of all IMID patients significantly increased from 33.8% to 51.1% (p<0.001, Figure 1). The vaccination coverage in IBD patients increased significantly from 75.9% to 86.3% for influenza (p<0.001), from 72.9% to 88.7% for pneumococci (p<0.001), from 66.0% to 80.2% for hepatitis B (p<0.001), from 79.9% to 85.7% for tetanus (p=0.041) and from 42.2% to 60.4% overall (p<0.001) (Figure 1 and Table 1). Similarly, the vaccination coverage significantly increased for rheumatology patients, namely from 69.3% to 78.3% for influenza (p<0.001), from 34.5% to 85.0% for pneumococci (p<0.001) and from 32.8% to 36.5% for hepatitis B (p<0.001) (Table 1). For patients with dermatological inflammatory conditions, vaccination coverage significantly increased from 60.5% to 81.6% for pneumococci (p=0.031) and from 47.1% to 55.3% for hepatitis B (p=0.002) (Table 1). Conclusion The suboptimal vaccination rate measured in 2018 and the COVID-19 pandemic stressed the importance of vaccination recommendations to patients and healthcare professionals. We here show that the implementation of a vaccination tool integrated in the electronic medical record of patients is correlated with a significant increase in specific vaccination rates and also in the total amount of IMID patients that were fully vaccinated according to guidelines. 1. Rahier JF, Magro F, Abreu C, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014;8:443–468.(Figure Presented)(Table Presented)
ABSTRACT
It was suggested that all SARS-CoV2 infections lead to development of specific IgG antibodies that remain detectable in time. Targeted Immune-Modulating Therapies (TIMT) for treatment of Immune Mediated Inflammatory diseases (IMID) could interfere with humoral immune response against COVID-19. To investigate the seroprevalence of SARS-CoV2 IgG in relation to previous exposure to COVID-19 and ongoing IMID treatment a cross-disciplinary, prospective observational cohort was set up at two Belgian university hospitals. Between 17/12/2020 and 28/02/2021, patients with IMIDs of the skin (psoriasis (PsO), hidradenitis suppurativa (HS), atopic dermatitis (AD)), gut or joints were asked to participate. Patients under conventional systemic treatment or TIMT were included. An electronic survey (REDCap®) and blood samples were obtained (SARS-CoV-2IgG Abbott–Architect kit®). Statistical analyses were performed with SPSS26. 2166 IMID patients consented to take part. 1913 completed the survey: 218 dermatology patients (77% PsO, 12% HS, 11% AD), 415 rheumatology and 1217 IBD patients. 372 patients (19.5%) reported having experienced symptoms suggestive of COVID-19: fatigue (61.3%) and headache (48.1%) were most frequent. 96 patients (5.04%) had a positive SARS-CoV2 PCR test on nasal or throat swab: in 45.8% anti-SARS-CoV2 IgG seroconversion was confirmed. There was no significant difference in seroconversion rate between the 2 treatment groups (P=0.192). Of the seroconverted group, 75.0% were treated with TIMT. Prevalence of COVID-19 symptoms and number of confirmed COVID-19 cases remain low in this IMID cohort, regardless of treatment modality. There was no significant difference in SARS- CoV2 IgG seroconversion rate between TIMT and conventional systemic treatment in patients with positive PCR.
ABSTRACT
Background: Immunomodulators (IMM) and Targeted Immune-Modulating Therapies (TIMT) such as anti-TNF, anti-interleukins and Janus Kinase inhibitors, for treatment of Immune Mediated Inflammatory diseases (IMID) could theoretically interfere with the cytokine storm and humoral immune response against COVID19 infection and vaccination. We investigate seroprevalence and evolution of SARS-CoV2 antibodies in relation to previous vaccination and/or exposure to COVID19 and ongoing IMID-treatment in a Belgian, reallife population of IMID patients. Methods: A cross-disciplinary, prospective, observational cohort study was set up at two university hospitals. All patients with IMIDs of the gut (Crohn's disease, ulcerative colitis), joints (rheumatoid, psoriatic or spondyloarthritis) and skin (psoriasis, hidradenitis suppurativa, atopic dermatitis) visiting the respective clinics were asked to participate. Patients had to fill out an electronic survey (REDCap®, based on WHO-ISARIC) and blood samples were drawn for serology testing (anti-Spike(S) and antiviral Nucleocapsid(N) protein antibody IgG, Abbott). Results at baseline, prior to the national vaccination program and at 6 months follow-up are presented. R version 4.0.2 was used for statistical analyses. Results: At baseline 2165 IMID patients consented to take part. In 3.2% SARS-CoV2 anti-N seroconversion was confirmed. Of the anti-N seroconverted patients 72.9% reported a positive PCR test prior to inclusion. At 6-months follow-up, data of 1853 IMID patients was collected. Of these, 81.7% were fully and 14.4% partially vaccinated. Seroconversion for anti-N antibodies was confirmed in 2.5% of all participants and seroconversion for anti-S antibodies in 90.8%. In 5.1% (61/1483) of fully vaccinated IMID patients no seroconversion in anti-N nor anti-S antibodies was found. Chi Square analyses show, at 6-months follow-up, no significant association between anti-S seroconversion rate and treatment with systemic steroids (RiskRatio 1.22, 95%CI 0.38-3.9, P=0.99), TIMT (RiskRatio 0.57, 95% CI 0.3-1.1, P=0.12), IMM (RiskRatio 1.65, 95% CI 0.85- 3.19, P=0.19) or combination treatment IMM/TIMT (RiskRatio 1.60, 95% CI 0.75-3.4, P=0.32). Appearance of COVID19 symptoms followed the epidemiological curve in Belgium (Fig1). Conclusion: In this real-life IMID cohort, the number of COVID19 cases confirmed by PCR prior to vaccination was low. Seroconversion rate for anti-N antibodies was lower at 6-months follow-up, suggesting decrease in antibody titre over time. Full COVID19 vaccination led to a high anti-S antibody seroconversion rate. Nonetheless, 5.1% of fully vaccinated patients showed no antibody seroconversion. So far, no significant association between anti-S antibody seroconversion and IMID treatment was noted.
ABSTRACT
Background: Patients with immune-mediated inflammatory diseases (IMID) are at higher risk for infectious diseases. Despite this increased risk and the available guidelines1, we reported a sub-optimal vaccination rate of 27.4% of IMID patients in 2018. In the meantime, a vaccination module was introduced in the electronic patient health record of our hospital to accurately document and monitor vaccination status of patients. The impact of this new module on vaccination coverage was re-evaluated in the same IMID patients in 2021. Methods: Between Aug and Oct 2021, the vaccination status of 1448 (out of the original 1488) IMID patients (44.8% male, median age 53.6 years) was collected (798 patients with IBD, 612 with rheumatological, and 38 with dermatological inflammatory conditions) and compared to that of 2018. The vaccination status was obtained mainly through the patients' electronic medical records. Missing data were added after contacting patients or their general practitioner. Results: From 2018 to 2021, the overall vaccination coverage of all IMID patients significantly increased from 27.4% to 51.9% (p<0.001, Figure 1). The vaccination coverage in IBD patients increased significantly from 75.9% to 86.3% for influenza (p<0.001), from 72.9% to 88.7% for pneumococci (p<0.001), from 66.0% to 80.2% for hepatitis B (p<0.001), from 79.9% to 85.7% for tetanus (p=0.041) and from 42.2% to 60.4% overall (p<0.001) (Figure 1 and Table 1). Similarly, the vaccination coverage significantly increased for rheumatology patients, namely from 69.3% to 78.3% for influenza (p<0.001), from 34.5% to 85.0% for pneumococci (p<0.001), from 32.8% to 36.5% for hepatitis B (p<0.001) and from 7.8% to 32.6% overall (p<0.001) (Figure 1 and Table 1). Conclusion: The suboptimal vaccination rate measured in 2018 and the COVID-19 pandemic stressed the importance of vaccination recommendations to patients and healthcare professionals. We here show that the implementation of a vaccination tool integrated in the electronic medical record of patients is correlated with a significant increase in specific vaccination rates and also in the total amount of IMID patients that were fully vaccinated according to guidelines.
ABSTRACT
Background: Belgium suffered considerably from the COVID19 pandemic with high hospitalisation rates during 2 periods: a first wave in March and April 2020, and a second starting from October until the end of 2020. Measures of lowering social interaction were taken throughout 2020 and intensified during the first and second wave when needed. This pandemic could have influenced the access to care and advanced therapies for patients with Rheumatoid Arthritis (RA). In the electronic platform “Tool for Administrative Reimbursement Drug Information Sharing” (TARDIS), data from all Belgian RA patients on biologic and targeted therapy are collected during the submission of a request for initiation and prolongation of reimbursement for these drugs. Objectives: to investigate the effect of the COVID19 pandemic on the monthly prescription behaviour of a new advanced therapy in 2020 by comparing it to 2019. Methods: Patients were selected for this analysis if they started a new TNFi, B/T cell therapy, IL6 inhibitors or tsDMARD therapy in the TARDIS registry in 2019 or in 2020. Rheumatologists request reimbursement via the online TARDIS tool, which is considered here as a new drug prescription. Prescription behaviour was compared between 2019 and 2020, between bionaive and bioexperienced patients, and between the different drug classes Results: In 2019, 2949 patients were prescribed any new advanced therapy, including 1153 TNFi, 469 B/T cell therapy, 436 IL6 inhibitors and 891 tsDMARDs. In 2020, 2998 patients were prescribed any new advanced therapy including 1233 TNFi, 382 B/T cell therapy, 496 IL6 inhibitors and 887 tsDMARDs. On a monthly basis, on average 246 and 250 new advanced therapies were prescribed in 2019 and 2020 respectively. Monthly deviations from this average in 2019 ranged from -19% to +16%. Monthly deviations from this average in 2020 ranged from -50% to +30%. Figure 1A shows the monthly prescription of new advanced therapies in 2019 and 2020. For bionaive and bioexperienced patients, the same trend can be noted. Monthly deviations in bionaive patients in 2020 ranged from -60% to +38%, compared to -18% to +21% in 2019. Monthly deviations in bioexperienced patients ranged from -40% to +25%, compared to -19% to +17% in 2019. Comparison per drug class in 2020 show similar trends. IL6 inhibitors show a slightly different timeline than other drugs classes with other periods of less or more prescriptions changes compared to the other drugs classes. See Figure 1B. Conclusion: The COVID19 pandemic did affect reimbursement requests for patients starting new advanced therapies in March and April 2020, especially for bionaive patients. The latter half of 2020 was apparently used to catch up with reimbursement requests for patients in need for advanced therapies resulting in similar total numbers of patients treated with advanced therapy in 2019 and 2020. The choice for a particular drug type was not clearly influenced by the pandemic. IL6 inhibitor use did seem to be affected differently by the pandemic, yet caution is warranted as these relatively large differences in proportional changes parallel small differences in actual drug numbers. In sum, the observed effect of the pandemic on initiating advanced therapy during the first wave corresponds with Belgian governmental measures that restricted non-essential care which was less observed in the latter half of 2020.