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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: Improvement in clinical outcomes and normalisation of objective markers of inflammation, high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP), are considered treatment targets per STRIDE-II guidelines.1 We evaluated the effect of the oral selective Janus kinase inhibitor upadacitinib (UPA) on changes in hs-CRP, FCP, and clinical outcomes in patients with Crohn's disease (CD). Method(s): In 2 phase 3, randomized, double-blind, placebo-controlled induction studies (U-EXCEL, NCT03345849;U-EXCEED, NCT03345836), patients with moderate-to-severe CD received 12-week treatment with UPA 45 mg (UPA45) once daily (QD) or placebo (PBO). Patients with clinical response to UPA45 were rerandomised in U-ENDURE (NCT03345823) to receive 52-week maintenance treatment with UPA 30 mg QD (UPA30), UPA 15 mg QD (UPA15), or PBO. Endpoints included marker normalisation (hs-CRP <= 5 mg/L, FCP <= 250 mug/g) in patients with elevated baseline marker levels, normal marker and clinical remission by Crohn's Disease Activity Index (CDAI < 150) or very soft/liquid stool frequency (SF)/abdominal pain score (APS) (average daily SF <= 2.8 and average daily APS <= 1, neither greater than baseline), and >= 50% reduction from baseline in marker values with a decrease of at least 100 points in CDAI from baseline. Median changes from baseline in marker levels were also evaluated. Non-responder imputation with no special data handling for missing data due to COVID-19 was used. Result(s): Of 1021 enrolled patients, 645 (63.2%) had elevated hs-CRP (> 5 mg/L) and 750 (73.5%) had elevated FCP (> 250 mug/g) levels at baseline. Significantly greater proportions of patients with elevated baseline marker levels achieved normalisation with UPA compared with PBO at week 12 (Fig 1A/B) and week 52 (Fig 2A/B;nominal P < .001 for all). Decreases in marker levels from baseline with UPA were observed as early as week 2 and were significantly greater than with PBO through week 12 (Fig 1C) and week 52 (Fig 2C;nominal P < .001 for all). Patients achieved clinical endpoints and improvements in markers at significantly higher rates with UPA45 vs PBO at week 12 (Fig 1D-F) and with UPA15 and UPA30 vs PBO at week 52 (Fig 2D-F;P < .001 for all). The safety profile of UPA in CD was previously reported and no new safety concerns were identified. Conclusion(s): Improvements in clinical endpoints and normalisation of objective markers of inflammation were achieved as early as week 2 with UPA45 induction and sustained with UPA15 and UPA30 maintenance therapy in patients with CD. Median changes in hs-CRP and FCP with UPA support continued improvement of inflammation up to week 52 .
ABSTRACT
Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. The long-term, Phase 3b/4 RIVETING study (NCT03281304) assessed the efficacy and safety of tofacitinib dose reduction from tofacitinib 10 mg twice daily (BID) maintenance therapy to 5 mg BID in patients (pts) in stable remission. 1 We present a final analysis of the RIVETING study after >=30 months of treatment. Method(s): RIVETING was a double-blind, randomised, parallelgroup study with a 42-month (M) duration. Eligible pts had received tofacitinib 10 mg BID for >=2 consecutive years in an open-label, long-term extension study (NCT01470612), had been in stable remission for >=6 months and corticosteroid-free for >=4 weeks prior to baseline. The primary efficacy endpoint was remission at M6 based on modified Mayo (mMayo) score (endoscopic and stool frequency subscores of <=1 and rectal bleeding subscore of 0).1 RIVETING was terminated (primary objective met) when all pts had passed M30 (or discontinued);some pts had already completed all visits up to M42. Here, we assess efficacy at M30 and safety throughout. Result(s): Overall, 140 pts were randomised (1:1) to tofacitinib 5 or 10 mg BID;50.0% and 62.9% were in remission based on mMayo score at M30 in the 5 and 10 mg BID dose groups, respectively, with consistent findings observed for other secondary efficacy endpoints (Table 1). At M30, observed differences for mMayo remission between tofacitinib 10 and 5 mg BID were generally greater in the subgroup with a baseline endoscopic subscore of 1 vs 0 and in the subgroup with vs without prior tumour necrosis factor inhibitor (TNFi) failure (Table 1). The percentage of pts who experienced loss of remission by M30, as estimated from Kaplan-Meier curves, was numerically higher in the 5 vs the 10 mg BID dose group (28.1%;95% confidence interval [CI], 17.68-39.49 vs 21.7%;95% CI, 12.21-32.95, respectively). Table 2 shows adverse events of special interest, by dose group. One death occurred due to fatal coronavirus disease 2019 pneumonia (10 mg BID). Conclusion(s): These long-term data showed that most pts in stable remission on tofacitinib 10 mg BID maintenance therapy maintained mMayo score remission through M30 after dose reduction to 5 mg BID. Dose group difference in remission at M30 was consistent with that at M6.1 Differences in remission between the tofacitinib 5 and 10 mg BID groups were greater in subgroups with an endoscopic subscore of 1 vs 0 and in subgroups with vs without prior TNFi failure. Overall, safety findings were consistent with tofacitinib's known safety profile;incidence of serious infections and herpes zoster was numerically higher in the tofacitinib 10 vs 5 mg BID group. (Table Presented).
ABSTRACT
Introduction: ABX464 (obefazimod) is an oral small molecule that modulates inflammation by upregulating a specific anti-inflammatory micro- RNA (miR-124). ABX464 has demonstrated safety and efficacy in patients with moderate-to-severe ulcerative colitis (UC) in a randomized, placebocontrolled, phase 2b induction study (NCT04023396)1. This analysis presents interim data at week 48 after enrollment in the open-label (OL) maintenance study. Aims & Methods: During the 16-week induction Phase 2b, patients received placebo or obefazimod 25mg, 50mg or 100mg once daily (od) and, irrespective of their clinical response, could enter the OL 96-week maintenance study with obefazimod 50mg od. Patients were enrolled into this study from January 13, 2020. Here we present data from an interim analysis cut-off date on Feb 13, 2022. Patients were followed monthly for safety and efficacy. Non-responder imputation (NRI) was used for missing efficacy data. All subjects were assessed for safety: treatment emergent adverse events (TEAEs), TEAEs leading to study discontinuation, serious adverse events (SAEs). Result(s): Of 222 patients who completed the phase2b induction study, 217 (97.7%) were enrolled in the OL maintenance study. 33/217 (15.2%) patients dropped out prior to week 48, mainly for UC worsening (10/33). All dropouts were considered as treatment failures for this interim analysis. Main efficacy results are presented in the table below. Among the 96 patients with no clinical response after induction, 42.7% achievedde novo clinical remission at week 48 of the OL maintenance study. Among the 52 patients with clinical remission after induction, 73.1% maintained clinical remission at week 48. In total, 139/217 subjects (64.1%) reported at least one TEAE. TEAEs leading to study discontinuation were reported in 15 subjects (6.9%) and serious adverse events (SAEs) were reported in 17 subjects (7.8%). The most frequent TEAEs (>= 5%) were headache (11.5%), COVID-19 (10.1%), ulcerative colitis (6.5%) and nasopharyngitis (5.9%). No new safety risks were identified over these initial 48 weeks. Conclusion(s): Results from this 48-week interim analysis of the OL maintenance Phase 2b study confirmed excellent long-term efficacy of obefazimod 50mg od in clinical responders and non-clinical responders after induction as well as a favorable long-term safety profile.
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Introduction: Etrasimod (APD334), an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator, demonstrated efficacy in adults with moderately to severely active ulcerative colitis (UC) in the Phase 2 OASIS trial (NCT02447302). Here, we report data from 2 trials, ELEVATE UC 52 and ELEVATE UC 12, that evaluated the efficacy and safety of etrasimod 2mg for induction and maintenance in adults with UC. Aims & Methods: ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) were global, randomized, double-blind, placebo-controlled trials. In both trials, adults (16-80 years) with moderately to severely active UC (based on modified Mayo Score [MMS] of 4-9 with centrally read endoscopic subscore >=2 and rectal bleeding subscore >=1) and documented history of inadequate response, loss of response, or intolerance to >=1 treatment for UC were randomized 2:1 to once-daily treatment with etrasimod 2mg or placebo. Patients (pts) were stratified by previous exposure to biologic/Janus kinase inhibitor (JAKi) therapy, baseline corticosteroid use, and baseline disease activity (MMS 4-6 or 7-9). ELEVATE UC 52 utilized a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. Beginning at Week (Wk) 12, all pts could continue their randomized treatment;pts whose disease had not improved or had worsened compared to baseline (based on investigator judgement) could discontinue and enroll in an open-label extension study (NCT03950232). ELEVATE UC 12 comprised a 12-week induction period only. The primary efficacy endpoints were the proportion of pts achieving clinical remission (using the MMS) at Wk 12 and Wk 52 in ELEVATE UC 52, and at Wk 12 in ELEVATE UC 12. Safety was evaluated throughout the trials. Result(s): In ELEVATE UC 52, 433 pts were randomized (etrasimod, n=289;placebo, n=144) and 207 completed Wk 52. In ELEVATE UC 12, 354 pts were randomized (etrasimod, n=238;placebo, n=116) and 316 completed Wk 12. 62.6% of etrasimod-treated pts in both trials and 61.8% and 62.9% of placebo-treated pts in ELEVATE UC 52 and ELEVATE UC 12, respectively, were naive to biologic/JAKi therapy. All primary and key secondary efficacy endpoints were achieved with etrasimod vs placebo at both Wks 12 and 52 in ELEVATE UC 52 and Wk 12 in ELEVATE UC 12 (Table). Most commonly reported TEAEs (>=3% of etrasimod-treated pts and greater than placebo in either trial) were headache, nausea, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain and worsening of UC. Serious AEs were similar between treatment groups in both trials. The overall safety profile was consistent with previous studies. Conclusion(s): Treatment with etrasimod 2mg resulted in statistically significant and clinically meaningful improvements based on clinical, endoscopic, symptomatic, and endo-histologic endpoints at Wks 12 and 52 in adults with moderately to severely active UC. No new safety findings were observed with etrasimod 2mg treatment for up to 52 weeks.
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 IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARS-CoV-2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods Clinical data and sera were collected from, 2,213 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, the United Kingdom, and the United States between, 26 May, 2020 and, 24 September, 2021 (Table, 1). Sera were taken prior to vaccination. Clinical data were collected through patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed, 99.4% concordance. Univariate analysis was performed to evaluate association between individual variables and sero-status. Results The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from, 0% in Hong Kong to, 57.9% in New Delhi, India (p<0.001). Rates in Europe and North America were similar (range, 3.57%-8.94%). Overall, SARS-CoV-2 seroprevalence appears to be equal to or less than local populations (Table, 2). Seroprevalence rates were associated with IBD type (7.8% CD, 12.4% UC, 15% IBD-U, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any IMM (p<0.001). (Table, 3). Whilst there were no significant differences in seroprevalence between patients receiving infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on IFX monotherapy and combination therapy (both p=0.002) and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion We confirm in diverse poulations that exposure to biologics or immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination.
ABSTRACT
Background: IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARSCoV- 2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods: Clinical data and sera were collected from 2,241 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, United Kingdom, and the United States between May 2020 and September 2021 (Table 1). Sera were taken prior to vaccination. Clinical data were collected from patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed 99.4% concordance. We performed univariate analysis to evaluate association between variables and sero-status. Results: The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from 0% in Hong Kong, China, to 57.9% in New Delhi, India. Rates in Europe and North America were similar (range 3.6%-8.9%). Overall, SARSCoV- 2 seroprevalence appears to be equal to or less than local populations (Table 1). Seroprevalence rates were associated with IBD type (Crohn's disease 7.8%, ulcerative colitis 12.4%, IBD-unclassified 15.0%, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any immunomodulator (IMM) (p<0.001) (Table 1). Infection as indicated by seropositivity in the absence of known COVID infection occurred in 7.3% of patients. Whilst there were no significant differences in seroprevalence between patients receiving anti-tumor necrosis factor (anti-TNF) medications, vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on anti-TNF monotherapy (p=0.002), anti-TNF + IMM combination therapy (p=0.002), and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion: We confirm in diverse populations that exposure to anti-TNFs, vedolizumab and immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination. (Table Presented) Table 1. Seroprevalence of total anti-SARS-CoV-2 spike antibodies in IBD patients by ICARUS centre with non-IBD controls noted for New Delhi, India, and publicly reported local seroprevalence and by selected patient characteristics.(Figure Presented) Figure 1. Antibody levels by medication group.
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: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. First market authorization was received in the US in May 2018. Post-marketing surveillance (PMS) is an important part of monitoring adverse events (AEs). Here, we report an analysis of PMS case safety reports for tofacitinib in patients with UC.Methods: We analyzed the worldwide tofacitinib PMS reports received in the Pfizer safety database from May 30, 2018 to August 25, 2020. The type and estimated reporting rate (RR) of serious AEs (SAEs) of interest, incl. infection, vascular, respiratory, neoplasm, and cardiac events, were reviewed. Patient-years of exposure (PY) was estimated based on worldwide sales data and the calculated daily regimens of tofacitinib 5 or 10 mg twice daily, immediate or extended-release formulations.Results: During the 27-month reporting period, worldwide post-marketing exposure to tofacitinib was 8,916 PY. Overall, 4,226 case reports were received and included 12,103 AEs, of which 1,839 were SAEs. Among the cases reported, 1,141 (27.0%) included an SAE and 18 (0.4%) were fatal. Of cases with reported gender (88.1%) or age (81.6%), 46.5%occurred in men and the median age was 45 years (range 9–93). When analyzed by tofacitinib formulation, proportions of SAE cases were similar (Table 1). Table 2 presents a summary of AEs and SAEs by MedDRA system organ class. Among the 1,839 SAEs, RRs per 100 PY were 3.28 for infection events, 1.26 for vascular events, 0.74 for respiratory events, 0.55 for neoplasm events, and 0.50 for cardiac events. The most commonly reported serious infection events (MedDRA preferred term [PT] n≥8) were 2 PTs within the high level term (HLT) of Clostridia infections (C. difficile colitis/infection), pneumonia, COVID-19, cytomegalovirus, and herpes zoster. The most commonly reported serious vascular events (n≥10) included hemorrhage, thrombosis, and deep vein thrombosis. Most serious respiratory events were pulmonary embolism. The most commonly reported serious neoplasm events (n≥3) were 2 PTs within the HLT of breast and nipple neoplasms malignant (breast cancer female/breast cancer), colon cancer, lymphoma, malignant melanoma, neoplasm malignant, and prostate cancer. The most commonly reported serious cardiac events (n≥4) were 3 PTs within the HLT of ischemic coronary artery disorders (acute myocardial infarction/myocardial infarction, angina pectoris) and pericarditis.Conclusion: Based on this review of PMS data for tofacitinib in UC, the types of AEs and RRs were consistent with the known tofacitinib safety profile, with no new potential risks identified. Limitations of PMS reports, low numbers of case reports for extended-release formulation, and reliance on estimated RRs due to lack of precise values for exposure, required for incidence rate calculation, should be considered when interpreting these results.(Table Presented)(Table Presented)
ABSTRACT
Introduction: Upadacitinib (UPA), an oral JAK inhibitor, showed significantly greater efficacy vs placebo (PBO) in induction treatment of patients (pts) with moderately-to-severely active ulcerative colitis (UC) in two phase 3 induction trials, U-ACHIEVE and U-ACCOMPLISH. We evaluated efficacy of UPA in pts who had an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR) or were non-Bio-IR. Methods: U-ACHIEVE and U-ACCOMPLISH, multicentre, double-blind, placebo (PBO)-controlled trials, randomized pts with moderately to severely active UC to UPA 45 mg QD or PBO for 8 weeks (wks). Randomization was stratified by status of previous biologic failure, ie an inadequate response (IR), loss of response, or intolerance to biologic therapies (Bio-IR or bio-failure) vs non-Bio-IR (nonbio-IR or non-bio-failure), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or>7). Efficacy endpoints included primary endpoint of clinical remission (adaptedMayo score) at Wk 8 and ranked secondary endpoints of clinical response (partial adapted Mayo score at Wk 2 and adapted Mayo score at Wk 8), endoscopic improvement (Mayo endoscopic subscore 0 or 1), endoscopic remission (Mayo endoscopic subscore 0) and histologic-endoscopic mucosal improvement at Wk 8 (HEMI;endoscopic subscore ≤1 and Geboes score ≤3.1). Results using non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported. Results: In both studies, approximately half the pts were Bio-IR (Table 1). In both Bio-IR and non-Bio-IR pts, significantly higher proportion of pts receiving UPA achieved primary endpoint of clinical remission versus PBO;the magnitude of clinical remission at Wk 8 was greater in non-Bio-IR pts (UPA, 35% vs PBO, 9%;treatment difference [95% CI]: 26.0% [16.0, 36.1]) versus Bio-IR (UPA, 18% vs PBO, 0%;17.5% [11.4, 23.6]) in U-ACHIEVE and non-Bio-IR (UPA, 38% vs PBO, 6%;31.6% [22.8, 40.5]) versus Bio-IR (UPA, 30% vs PBO, 2%;27.1% [19.6, 34.7];Table 1) in U-ACCOMPLISH. Results were generally similar for ranked secondary endpoints (Table 1). UPA 45 mg QD was well-tolerated and no new safety signals were observed. Conclusion: UPA 45 mg QD is an effective induction treatment for pts with moderately to severely active UC. A significantly higher proportion of pts in both Bio-IR and non-Bio-IR groups receiving UPA achieved primary and secondary endpoints versus PBO. The magnitude of difference was greater among pts who were non-Bio-IR versus Bio-IR.
ABSTRACT
Introduction: U-ACCOMPLISH is one of two phase 3 induction trials evaluating safety and efficacy of upadacitinib-45 mg once daily (UPA) in adults with ulcerative colitis (UC). Methods: U-ACCOMPLISH, a multicentre, randomized, double-blind, placebo-controlled trial (NCT03653026), enrolled patients (pts) with moderate-to-severe UC (defined as adapted Mayo score 5-9 with centrally read endoscopic score of 2-3) who had inadequate response, loss of response, or intolerance to aminosalicylates, immunosuppressants, corticosteroids and/or biologics. Pts were randomized 2:1 to UPA or placebo (PBO) for 8 weeks (wks). At wk 8, responders entered the maintenance phase and non-responders entered the extended treatment period to receive open-label UPA for additional 8 wks. Primary endpoint (clinical remission per adapted Mayo Score) and ranked secondary endpoints including symptomatic, endoscopic-histologic evaluations from 8-wk PBO-controlled period are reported here. Non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported. Results: 522 pts were randomized (UPA, n = 345;PBO, n = 177);intent-to-treat population included 341 pts in UPA and 174 pts in PBO group. Baseline demographics and disease characteristics were similar between groups;50.7% and 51.1% were biologic inadequate responders in UPA and PBO groups, respectively (Table 1). A significantly higher proportion of pts receiving UPA (33.5%) versus PBO (4.1%) achieved primary endpoint (adjusted treatment difference: 29.0% [23.2, 34.7];P<0.001). A significantly higher proportion of pts receiving UPA versus PBO also achieved all ranked secondary endpoints (all P<0.001;Figure 1).Serious adverse events were reported by 3.2% and 4.5% of pts in UPA and PBO groups, respectively (Table 1). Similar rates of serious infection were observed in both groups (0.6%);2 events each of herpes zoster and opportunistic infection were reported in UPA group. No active tuberculosis, malignancy, adjudicated major adverse cardiovascular events, or deaths were reported. One pt with venous thromboembolism (deep vein thrombosis and pulmonary embolism) and 1 pt with gastrointestinal perforation were reported in the placebo group. Conclusion: UPA 45 mg QD induction treatment led to statistically significant improvements in clinical, endoscopic, and combined endoscopic-histologic endpoints. Treatment was well tolerated, and safety profile and AE prevalence were comparable with previous studies of UPA with no new safety signals identified.
ABSTRACT
Introduction: U-ACHIEVE is one of two phase 3 induction trials evaluating safety and efficacy of the selective JAK-1 inhibitor upadacitinib-45 mg once daily (UPA) in adults with ulcerative colitis (UC). Methods: U-ACHIEVE, a multicentre, double-blind, placebo (PBO)-controlled trial (NCT02819635) randomized patients (pts) with moderately-to-severely active UC 2:1 to UPA or PBO for 8 weeks (wks). Randomization was stratified by biologic inadequate responder (Biologic-IR) status (Biologic-IR vs non-biologic-IR), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or≥7). Primary endpoint was proportion of pts achieving clinical remission (per adapted Mayo Score) at wk 8. Ranked secondary endpoints included wk 8 endoscopic improvement, endoscopic remission, clinical response per adapted Mayo Score, and histologic-endoscopic mucosal improvement;and wk 2 clinical response per partial adapted Mayo Score. Non-responder imputation incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through wk 8. Results: 474 pts were randomized (UPA, n=319;PBO, n=155). Baseline characteristics were well balanced between groups (Table 1). A significantly higher proportion of pts receiving UPA (26.1%) vs PBO (4.8%) achieved wk 8 clinical remission (adjusted treatment difference [95% CI]: 21.6% [15.8, 27.4];P<0.001;Figure 1a). For all ranked secondary endpoints, UPA was superior to PBO (P<0.001;Figure 1a). A significant difference vs PBO in clinical response favouring UPA was seen as early as wk 2 (60.1% vs 27.3%) and was sustained thereafter up to wk 8 (79.0% vs 41.6%;Figure 1b). Serious AEs, severe AEs, and AEs leading to study drug discontinuation were higher in PBO group (Table 1). Acne, creatine phosphokinase elevation, and nasopharyngitis were most common AEs with UPA and worsening UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO (Table 1). No adjudicated gastrointestinal perforation, major adverse cardiovascular events, or thrombotic events, and no active tuberculosis, malignancy, or deaths were reported. Conclusion: In pts with moderately-to-severely active UC, UPA induction therapy was superior to PBO in inducing clinical and endoscopic remission/response, over 8 wks;responses were significant and rapid. UPA was well-tolerated;safety was comparable with the known safety profile of UPA, and no new safety signals were identified.
ABSTRACT
The growing demand for online work with children, youngsters and their families during the Covid19 pandemic presented new challenges. The well-trodden roads had to be left. In this article we explore novel online ideas in systemic and narrative therapy. Playfulness in online work invites curiosity, vividness and collaboration, and vice versa. We conceive of it as an antidote for pitfalls and as an inspiration for responses to the threat of reductionism that lurks around the corner, especially in online work. It offers a stepping stone to a serious exploration and sharing of experiences, stories and meanings that help to develop richer understandings and more creative ideas. It is a source of new ways of relating for family members as well as for the therapist and the family. Finally, playfulness enables the weaving of threads and experiencing a sense of continuity between sessions. We illustrate our quest using several case stories. Practitioner points: Playfulness as an atmosphere, attitude and intervention in online work invites curiosity, vividness and collaboration (and vice versa) while opening new therapeutic possibilities. Keeping a broad systemic scope and inviting members of the actual and imaginary network works as an antidote to the threat of reductionism in online therapy. A playful use of the online medium creates new relational dances between family members as well as between the therapist and the family. © 2021 Association for Family Therapy and Systemic Practice in the UK