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Introduction: There are scant data on long-term outcomes of treatment of inflammatory bowel disease (IBD) with a combination of advanced therapies, including after de-escalation. Method(s): We identified patients with IBD at a tertiary center who began therapy with vedolizumab (VDZ) in combination with another advanced therapy (biologic or JAK inhibitor) between 2016 and 2020 and examined their outcomes through 6/1/22. We defined biochemical remission as CRP, 5 mg/L and calprotectin < 150 mcg/g, and endoscopic remission as Mayo endoscopic subscore 0 or simple endoscopic score for Crohn's disease (CD) 0. Short-term outcomes of this cohort were previously reported. Result(s): Fourteen patients with a median of 322 (IQR 251-322) weeks of follow up were identified. 10 had ulcerative colitis, 3 CD, and 1 indeterminate colitis. VDZ was combined with tofacitinib in 9 patients, ustekinumab in 3 and adalimumab in 2. Median time on combination therapy was 94 weeks (IQR 17-133). Eight patients achieved objective remission (3 biochemical, 5 endoscopic), 1 changed combination with subsequent endoscopic remission, 2 had primary non-response, 1 had secondary non-response, 1 stopped within 1 month due to reported adverse effect (paresthesia), and 1 lacked follow-up data. Eight patients de-escalated to a single agent, 4 at physician direction and 4 due to insurance denial. Before de-escalation, 6 had objective remission (2 biochemical, 4 endoscopic). After de-escalation, 3 patients maintained objective remission (2 biochemical, 1 endoscopic), 3 had disease flare, of which 1 required colectomy, and 2 lacked data. All 3 patients with disease flare had de-escalated following an insurance denial. Two patients remained on combination therapy through follow up: 1 has endoscopic remission after changing one drug of their combination and 1 has ongoing moderate endoscopic disease despite combination therapy. There were 2 infections requiring hospitalization (rotavirus, C. difficile), and 8 non-serious infections (5 mild SARS-COV-2, 1 peristomal cellulitis, 1 pneumonia, 1 sinus) while on combination therapy. Conclusion(s): In long-term follow up of this small cohort, there were no new signals on effectiveness or safety of combining advanced agents. De-escalation to a single agent was tolerated in half of patients with follow-up data;all patients who flared following de-escalation had adjusted therapy due to insurance denial. More data is needed to inform de-escalation decisions.
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Introduccion: Estudiamos el impacto del COVID-19 en pacientes con Enfermedad Inflamatoria Intestinal (EII) en Castilla-La Mancha. Metodos: Estudio observacional retrospectivo utilizando inteligencia artificial con capacidad de procesamiento de lenguaje natural, SAVANA manager. Esta herramienta, a pesar de sus sesgos (ej: duplicacion de casos), permite analizar grandes poblaciones. Analizamos datos de 1.808.010 pacientes durante 2020. Resultados: Se identificaron 2.243 pacientes con EII y COVID-19, que en comparacion con los casos de COVID-19 sin EII hubo mas hipertension arterial, diabetes mellitus, dislipemia, obesidad o tabaquismo. A pesar de ello, no se apreciaron diferencias en hospitalizacion (0,8607, 0,7320-1,0121, p = 0,0696), ingreso en UCI (0,4113, 0,1025-1,6508, p = 0,2102) o mortalidad (0,9099, 0,6123-1,3521, p = 0,6402). COVID-19 fue mas frecuente en pacientes con EII (3,6413, 3,4616-3,8303, p < 0,0001). Comparando pacientes con EII y COVID-19 segun sus tratamientos, vedolizumab es el unico con mayor riesgo de COVID-19 (0,3091, 0,0967-0,9886, p = 0,0478), sin embargo, el riesgo de hospitalizacion para vedolizumab es menor (0,3091, 0,0967-0,9886, p = 0,0478). Los inmunomoduladores tambien tienen un menor riesgo de hospitalizacion tanto solos (0,6677, 0,4650-0,9588, p = 0,0287) como combinados con anti-TNF (0,5109, 0,2836-0,9205, p = 0,0254). No se encontraron diferencias para monoterapia anti-TNF, ustekinumab o tofacitinib. La tasa de UCI y la mortalidad no son diferentes entre los tratamientos, salvo para tofacitinib (tasa de UCI 0,00%, mortalidad 10,00%), sin embargo, el pequeno numero de pacientes podrian sesgar este resultado. [Table presented] Conclusiones: COVID-19 en pacientes con EII no es diferente en hospitalizacion, ingreso en UCI o mortalidad en comparacion con la poblacion sin Ell. Los pacientes con Ell expuestos a inmunomoduladores y vedolizumab tienen menor riesgo de hospitalizacion que los no expuestos, no se encontraron diferencias para anti-TNF monoterapia o ustekinumab.Copyright © 2023 Elsevier Espana, S.L.U. Todos los derechos reservados.
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Background: Inflammatory bowel disease (IBD) may be associated with a more severe course of infections and a different response to vaccination, especially in complicated IBD course and in association with immune-modifying IBD treatment. The aim of this study was to describe COVID-19 pandemic during years 2020 2022 in IBD patients with long-Term biological therapy. Method(s): A retrospective analysis of SARS-CoV-2 infection incidence in the population of 1,177 IBD (Crohn s disease or ulcerative colitis) patients with long-Term biological therapy (IBD cohort) was performed. The incidence rate, crude incidence rate and standardized incidence ratio of COVID-19 in the IBD cohort, the odds ratio of infection depending on the type of biologic therapy administered, the dynamics of COVID-19 incidence depending on the predominant SARS-CoV-2 variant in the population and the current vaccination coverage of the IBD cohort were calculated. Result(s): From January 2020 to April 2022, 548 confirmed cases of COVID-19 (46.6%) were reported in the IBD cohort, with 39% share of PCR positivity in vaccinated individuals and with 95% occurrence of infection in unvaccinated part of the IBD cohort. Standardized incidence rate ratio of COVID-19 was 27% higher in the IBD cohort compared to the general Czech population. The dynamics of the development of the number of positive cases of COVID-19 in the IBD cohort was identical to the situation in the entire country. A higher odds ratio of the chances of infection was demonstrated in patients treated with tumor necrosis factor inhibitors, but not in patients treated with anti-integrins or monoclonal antibodies against interleukins. In the IBD cohort, 85.2% of patients were properly vaccinated, which was significantly more than the vaccination rate of the entire Czech population. Discussion and conclusion: During the two pandemic years, the incidence of COVID-19 in patients with severe IBD and long-Term biological treatment was higher compared to the general Czech population, despite the favorable vaccination coverage of this high-risk patients group. A higher risk was associated with tumor necrosis factor inhibitor therapy.Copyright © 2023 Galen s.r.o.. All rights reserved.
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The coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 virus led to a worldwide pandemic. Emergency use of an investigational medication, Paxlovid, was approved for patient 12 and older who tested positive for COVID-19 and at high risk for severe infection. Inflammatory Bowel Disease (IBD) is a chronic condition causing inflammation in the gastrointestinal tract. Ulcerative Colitis (UC) is a type of IBD centralized in colon and commonly treated with Immunosuppressive drugs. We present an adolescent with UC treated with paxlovid due to being on tacrolimus who developed with suspected tacrolimus toxicity. CASE REPORT: A 13-year-old female with UC presented to the ED with vomiting and fatigue after paxlovid ttreatment for COVID. The patient's UC treatment included tacrolimus along with ustekinumab. She had been diagnosed with SARS-CoV-2 and prescribed Paxlovid bid x 5 days due to immunosuppressive status. Tacrolimus was held during treatment. Once paxlovid completed, tacrolimus was restarted. Two days later, patient presented to ER for vomiting, fatigue, headaches and myalgia. Labs revealed a tacrolimus level of >60 ng/ml. Electrolytes and Creatinine were normal. Toxicology felt this was due to interaction between paxlovid and tacrolimus. Patient advised to hold tacrolimus for 48 hours and repeat levels were 15.8 ng/mL. Symptoms resolved and level repeated three days later and was 2.9 ng/mL. DISCUSSION: Tacrolimus is an immunosuppressant, commonly used for management of organ transplants but also been found effective in treatment of IBD. Tacrolimus requires close monitoring as toxicity may lead to acute or chronic kidney disease. The normal concentration is between 5-15 ng/mL. Due to rapid escalation of the COVID-19 pandemic, Paxlovid was approved for emergency use for treatment of high-risk patients. It is administered as a 5-day oral course consisting of nirmatrelvir and ritonavir. Our patient was prescribed Paxlovid due to risk secondary to immunosuppression. She was appropriately instructed to stop tacrolimus. Ritonavir is a cytochrome P450 3A inhibitor and can increase plasma concentration of tacrolimus. She restarted tacrolimus treatment 12 hours after her last dose of Paxlovid and presented with symptoms and a level consistent with toxicity. This level was concluded to be due to drug interaction between tacrolimus and Paxlovid. After further withholding of tacrolimus, symptoms improved, and levels normalized. Previous reports in transplant population stress importance of decreasing the dose of tacrolimus or withholding during the course of paxlovid treatment. This case demonstrates the importance of not only ceasing tacrolimus when administering paxlovid, but continuing discontinuation for longer period post completion of therapy to minimize interactions.Copyright © 2023
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Background: Coronavirus disease 2019 (COVID-19) has been a pandemic that is still very prevalent. Patients with Inflammatory Bowel Disease (IBD) represent a special population considering their already altered immune system and their exposure to several immunosuppressive therapies. We pretend to study the impact of COVID-19 on IBD patients in our community, Castilla-La Mancha (a region in central Spain). Method(s): Retrospective observational study using an artificial intelligence with natural language processing capability, the SAVANA manager, we analyzed data from 1 808 010 patients with Electronic Medical Records (EMR) within the public health system of Castilla-La Mancha from March 1st 2020 to January 1st 2021. Data on demographic characteristics, hospitalization, ICU admission and mortality were collected. We compared COVID outcomes between IBD and non-IBD patients. We compared COVID outcomes in IBD patients according to their treatment (comparing each treatment group to those IBD patients with no treatment);we considered: Immunomodulators (azathioprine, mercaptopurine, methotrexate), antiTNF alone or combined with immunomodulator, vedolizumab, ustekinumab and tofacitinib;mesalazine and corticosteroids were not analyzed. Result(s): 2 243 patients with IBD suffered COVID-19, compared to COVID-19 cases without IBD there were less females, they suffered more arterial hypertension, diabetes mellitus, dyslipidemia, obesity, or tabacco use (TABLE 1). And yet, despite these being proven risk factors for worse outcomes for COVID-19, no differences were appreciated in hospitalization rate, ICU admission, or mortality between those with or without IBD (TABLE 2). COVID-19 was more frequent in IBD patients (32.59 vs 13.28%). Comparing IBD patients with COVID-19 according to their treatments (TABLE 3), vedolizumab is the only treatment with a higher risk for COVID-19 infection, however the hospitalization risk for vedolizumab is lower than for those without it. Immunomodulators do also have a lower hospitalization risk both alone or in combination with antiTNF, no differences were found for antiTNF monotherapy, ustekinumab or tofacitinib. ICU rate and mortality are no different between treatments, except for tofacitinib (0.00% ICU rate, 10.00% mortality), however the small number of patients using this treatment may bias this result. Conclusion(s): COVID-19 in IBD patients is no different in hospitalization, ICU admission or mortality compared to non-IBD population. IBD patients exposed to immunomodulators and vedolizumab have less hospitalization risk than those not exposed, no differences were found for antiTNF alone or ustekinumab. The impact of tofacitinib in COVID outcomes requires further investigation.
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Background: The prevalence of nonadherence to major treatments and the subsequent adverse outcomes in IBD patients during the first wave of COVID-19 pandemic remain scarce Aim: To investigate the risk of early disease relapse in a cohort of IBD patients under immunosuppressants and/or biologics who decided themselves to discontinue their IBD-related major treatments without previous medical advice during the first wave of COVID-19 pandemic Methods: All consecutive patients with inactive IBD under immunosuppressants and/or biologics who acknowledged having withdrawn their major therapy for IBD without previous medical advice during the first wave of COVID-19 (from March 2020 to December 2020) were enrolled. The primary endpoint was the survival rate without disease relapse. Kaplan-Meier curves were plotted for time from inclusion to IBD relapse and a logistic regression model with uni- and multivariate analyses was performed to identify predictors of relapse after drug discontinuation Results: During the study period, among the 862 IBD patients followed as outpatients either treated with infliximab or vedolizumab (outpatient clinics n= 368) or treated with oral azathioprine, adalimumab golimumab or ustekinumab alone or in combination (n= 494), 54 patients (6.2 %) (42 CD, 12 UC, 28 F, median age 36 years) who had discontinued themselves their IBD-related major therapy without previous medical advice were included. The median duration of drug withdrawal was 7.0 weeks (range 2-24) and the median time to relapse was 9.0 weeks (range 4-20). The most treatments withdrawn were adalimumab (n=19), ustekinumab (n=19), azathioprine (n= 12), golimumab (n=1) and a lesser degree infliximab (n=7) eand vedolizumab (n=6). During the median follow-up period of 24 weeks (range 5-42), 22 out of 54 patients (40.7 %) who discontinued their IBD treatment experienced a relapse in whom 6 requiring administration of oral steroids, 4 hospitalization and 2 IBD-related surgery By univariate analysis, past IBD related surgery was identified as the only predictor of disease relapse after drug withdrawal (OR=3.3 CI 95 % [1.08-10.38] Conclusion(s): In IBD patients, major treatment discontinuation by the patients themselves without medical advices during the first wave of pandemic Covid-19 including the lockdown was associated with a substantial risk of disease relapse occurring in around 4 out of 10 patients and subsequent further risk of need for steroids, hospitalization and surgery. Strategies targeting the adherence to therapy and patient's informations about the real risks leading to drug discontinuation are of paramount interest, especially during health crisis to minimize such issues.
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Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .
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Background: The effects of immunosuppressive medications on immune responses to COVID-19 vaccination in patients with inflammatory bowel diseases (IBD) have been reported. However there is little data on immune responses in naturally infected SARS-CoV-2 patients compared with vaccination. We compared in a longitudinal study SARS-CoV-2 antibody and T cell responses in naturally-infected vs. vaccinated IBD patients Methods: 110 IBD patients enrolled at the Icahn School of Medicine at Mount Sinai were prospectively followed with serial blood collection between May 2020, and February 2022. Samples were screened by ELISA to determine seropositivity, and stratified by infection, vaccination status, and IBD medications. Subsequently, ELISA-based inhibition assay and pseudotyped SARS-CoV-2 microneutralization assays were used to determine the inhibition and neutralization capacity of the seropositive individuals for wild type (WT) delta variant (Dv) and Omicron. Cellular responses were measured by IFN-gamma ELIspot using nucleocapsid and spike peptide libraries Results: Overall, 64 patients had Crohn's Disease and 46 had Ulcerative Colitis (UC), 69 were naturally infected. Only Anti-TNF (N=52), Ustekinumab (N=16), and Vedolizumab (VDZ) (N=33) treatment groups were considered. Only US-available vaccinations were included. Double-vaccinated IBD patients showed greater neutralizing responses to SARS-CoV-2 WT and Dv than naturally-infected individuals (p=0.0003, p=0.0025). Moreover, double-vaccinated individuals had greater neutralizing reactions against WT than DV (p 0.017) and Omicron (p 0.001) variants. Following natural infection, there were no differences between treatment groups in neutralization response, however those double-vaccinated on anti-TNF had lower neutralization than VDZ (p=0.008). Neutralization responses were maintained for a period of 8 months following natural infection and double vaccination SARS-CoV-2 spike T cell responses were significantly higher in naturally infected (p=0.009) and double vaccinated individuals (p=0.005) with no significant differences between treatment groups (p<0.999) Conclusion(s): After a second vaccine dose, IBD patients showed stronger neutralizing antibody titers than naturally infected patients. Those on anti-TNF exhibited lower neutralizing responses than VDZ. T-cell responses were similar in infected and double-vaccinated subjects after vaccination or infection. These data imply COVID-19 immunization provides additional serological protection over natural infection.
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Background: Ustekinumab (UST) is a fully human IgG1k monoclonal antibody to human IL-12/23p40 approved in several jurisdictions for the treatment of adult patients with moderately to severely active Crohn's disease (CD). UST's impact on induction and maintenance of mucosal healing, fistula healing and extraintestinal manifestations were not fully elucidated in the registration trial program. Method(s): In this prospective, multicenter study (EudraCT number: 2017-005151-83) across all care levels in Germany, we evaluated the real-world effectiveness of UST prescribed within its German label to achieve the primary endpoint of combined clinical (Harvey Bradshaw Index (HBI) score reduction >= 3 points from baseline) and endoscopic (50% reduction of the simple Endoscopic Score for Crohn Disease (SES-CD) from baseline) response in week 52 and a variety of secondary endpoints including mucosal healing defined as the complete absence of mucosal ulcerations in any ileocolonic segment and endoscopic remission defined as an SES-CD score of 0 - 2. Result(s): We recruited 52 CD patients (female n=28, bionaive n=13, bioexposed n=39). See Table 1 for baseline demographics and pertinent history details. At week 52, 50% (n=12/24) of patients achieved the primary endpoint [50% (n=3/6) in the bionaive, 45.5% (n=5/11) bioexposed to one and 57.1% (n=4/7) bioexposed to multiple biologics cohorts, respectively], 58.3% (n=14/24) of patients achieved endoscopic response [50% (n=3/6) in the bionaive, 54.5% (n=6/11) bioexposed to one and 71.4% (n=5/7) bioexposed to multiple biologics cohorts, respectively], 33.3% (n=8/24) of patients achieved endoscopic remission [50% (n=3/6) in the bionaive, 27.3% (n=3/11) bioexposed to one and 28.6% (n=2/7) bioexposed to multiple biologics cohorts, respectively], 45.8% (n=11/24) of patients achieved mucosal healing [50% (n=3/6) in the bionaive, 36.4% (n=4/11) bioexposed to one and 57.1% (n=4/7) bioexposed to multiple biologics cohorts, respectively]. 36 patients (69.2%) experienced >= 1 treatment emergent adverse event (TEAE), in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to discontinuation of UST, but no very severe events or deaths (Table 2). Conclusion(s): UST reliably induces endoscopic response and mucosal clinical practice. The limited samples size is a direct result from the Covid-19 pandemic. No new safety signals were recorded.
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The coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 virus led to a worldwide pandemic. Emergency use of an investigational medication, Paxlovid, was approved for patient 12 and older who tested positive for COVID-19 and at high risk for severe infection. Inflammatory Bowel Disease (IBD) is a chronic condition causing inflammation in the gastrointestinal tract. Ulcerative Colitis (UC) is a type of IBD centralized in colon and commonly treated with Immunosuppressive drugs. We present an adolescent with UC treated with paxlovid due to being on tacrolimus who developed with suspected tacrolimus toxicity. CASE REPORT: A 13-year-old female with UC presented to the ED with vomiting and fatigue after paxlovid ttreatment for COVID. The patient's UC treatment included tacrolimus along with ustekinumab. She had been diagnosed with SARS-CoV-2 and prescribed Paxlovid bid x 5 days due to immunosuppressive status. Tacrolimus was held during treatment. Once paxlovid completed, tacrolimus was restarted. Two days later, patient presented to ER for vomiting, fatigue, headaches and myalgia. Labs revealed a tacrolimus level of >60 ng/ml . Electrolytes and Creatinine were normal. Toxicology felt this was due to interaction between paxlovid and tacrolimus. Patient advised to hold tacrolimus for 48 hours and repeat levels were 15.8 ng/ mL. Symptoms resolved and level repeated three days later and was 2.9 ng/mL DISCUSSION: Tacrolimus is an immunosuppressant, commonly used for management of organ transplants but also been found effective in treatment of IBD. Tacrolimus requires close monitoring as toxicity may lead to acute or chronic kidney disease. The normal concentration is between 5-15 ng/mL. Due to rapid escalation of the COVID-19 pandemic, Paxlovid was approved for emergency use for treatment of high-risk patients. It is administered as a 5-day oral course consisting of nirmatrelvir and ritonavir. Our patient was prescribed Paxlovid due to risk secondary to immunosuppression. She was appropriately instructed to stop tacrolimus. Ritonavir is a cytochrome P450 3A inhibitor and can increase plasma concentration of tacrolimus. She restarted tacrolimus treatment 12 hours after her last dose of Paxlovid and presented with symptoms and a level consistent with toxicity. This level was concluded to be due to drug interaction between tacrolimus and Paxlovid. After further withholding of tacrolimus, symptoms improved, and levels normalized. Previous reports in transplant population stress importance of decreasing the dose of tacrolimus or withholding during the course of paxlovid treatment. This case demonstrates the importance of not only ceasing tacrolimus when administering paxlovid, but continuing discontinuation for longer period post completion of therapy to minimize interactions.
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Biological therapies are increasingly being used in dermatology to treat conditions such as psoriasis and eczema. These medications are prescribed and dispensed in secondary care;however, it is important that they are present in the patient's primary care record, as this is often used by both the primary care provider and the hospital clerking doctor when the patient presents with other health concerns. Biologics are immunosuppressive medications, and it is thus important that any practitioner treating a patient who has been prescribed them is aware of this. Using a departmental record, all patients prescribed biological therapies or subcutaneous methotrexate were identified (n = 157). Their primary care medication record was then interrogated to assess whether the biological therapy was recorded. Forty-five (29%) patients on biological therapies or subcutaneous methotrexate did not have this recorded on their general practitioner (GP) record. The most common medications not recorded were ustekinumab (n = 14) and dupilumab (n = 13). There was no clear pattern indicating that a particular GP surgery was recording these medications poorly, and the patients were cared for evenly between the dermatology consultants in the department. This brief piece of work demonstrates that there is a problem with these prescriptions being accurately recorded on the GP record. Almost one-third of patients in the department did not have their biological therapy listed on their primary care record. Practitioners must be aware that a patient is on an immunosuppressive medication, especially when diagnosing and treating infections and assessing patient priority for COVID-19 vaccination, as well as including the need to avoid live vaccines. Furthermore, the GP record was used by Welsh Government agencies to identify patients needing to shield during the COVID-19 pandemic. These 45 patients recognized in the study would not necessarily have been identified as potentially high risk (depending on other comorbidities) and may therefore not have been advised to shield (in line with British Association of Dermatologists guidance for self-isolation and immunosuppressed patients). To rectify this problem in the short term, each GP surgery was contacted regarding the particular patients identified and were advised to add their biological therapy to their primary care record. Discussions between primary and secondary care and pharmacy are ongoing in order to identify how to prevent this problem from continuing.
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Background: COVID-19 vaccination has been suggested as very effective in patients with Inflammatory Bowel Disease (IBD), but most studies assess antibody levels within a few weeks after vaccination and do not use the most recent recommendations as seroconversion cut-off. The objective of VACOVEII study is to evaluate the antibody response to vaccination at 6 months using these recommendations, the improvement after a booster dose and the effect of the immunosuppressive therapy (IST). We present the intermediate results of the study. Method(s): Spanish multicentre, prospective and case-control study. 18 years or older IBD patients fully vaccinated against COVID-19 were included. Those with previous COVID infection were not included, but not excluded for the next analyses if the infection was subsequent. Main outcomes were anti-SARS-CoV-2 spike protein antibody (anti S) concentrations and rate of seroconversion (defined above the protection threshold of 260 BAU/mL), measured 6 months after vaccination at a single centralized laboratory. The effect of IST on the main outcomes was analysed, adjusted by age, vaccine type and COVID infection. Groups of treatment considered for the analysis were: Patients without IST (without treatment or under salicylates alone), anti-TNF in combination with immunomodulators (IMM), anti-TNF in monotherapy, IMM in monotherapy, ustekinumab and anti-integrin. Result(s): We included 313 patients with IBD (46.5% ulcerative colitis and 52.3% Crohn's disease, median age 49 years) vaccinated either with non-mRNA vaccines (14%) or mRNA vaccines (86%). Baseline therapy was: 124 patients without IST, 21 with anti-TNF plus IMM, 67 with anti-TNF in monotherapy, 54 with IMM in monotherapy, 28 with ustekinumab and 19 with anti-integrin. Mean anti S concentrations were significant lower in patients with anti-TNF compared with patients without IST (Figure 1). In multivariable analysis, lower antibody concentrations were independently associated with anti-TNF treatment, non-mRNA vaccines and older age. Within the patients with no COVID infection during the follow-up, we found very low rates of seroconversion in patients with anti-TNF (14.1%), ustekinumab (30.8%) and IMM in monotherapy (34.9%), compared with patients without IST (51.5%) (Table 1). In multivariable analysis, anti-TNF treatment, non-mRNA vaccines and older age were independently associated with lower rates of seroconversion, as well as ustekinumab and IMM in monotherapy (Table 2). Conclusion(s): COVID-19 vaccine-induced antibody seroconversion in patients with IBD, measured at 6 months and according to >260 BAU as protection threshold, is clearly lower than previously reported, with a profound impact by some IST therapies, mainly anti-TNF, besides age and type of vaccine.
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Psoriasis is a chronic inflammatory skin condition characterized by scaly erythematous patches or plaques affecting the extensor surfaces that are prominent but spreading to all areas of the body, including the flexor surfaces. Psoriasis occurs when the body's immune system attacks the skin;the interleukin (IL)-12 and IL-17/23 axes play a major role in its pathogenesis. Biologic therapies targeting IL-17 or IL-23 have emerged as an important treatment option for psoriasis and have led to substantial improvements in patients' quality of life. This systematic review aimed to evaluate the comparative efficacy and safety of secukinumab, ustekinumab and guselkumab for the treatment of moderate to severe plaque psoriasis. Based on the final analysis, there were 10 articles, namely 5 RCTs and 5 observational. We found that patients who were given secukinumab showed a rapid response, whereas guselkumab was superior in terms of long-term response (approximately 1 year) and complete remission compared to other biologics. Among all the biologics assessed, ustekinumab showed relatively low efficacy.
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To date, adalimumab (ADA) is the only biotechnology drug approved for the management of hidradenitis suppurativa (HS), an inflammatory skin condition. However, it quickly became apparent that the efficacy of adalimumab in daily practice was highly variable. In our review, we highlighted the current evidence from literature on the use of biologics in HS in a real-life setting, particularly adalimumab, secukinumab and ustekinumab. Data on the effectiveness and safety of biologic drugs in HS management have been analyzed. Even if the results are promising, more studies are needed. In our opinion, the armamentarium of drugs for HS management is increasing, and treatment will be based on a tailored-tail approach, minimizing the risk of adverse events. In this context, we want to point out the reported effectiveness and safety data concerning adalimumab, ustekinumab and secukinumab as well as ixekizumab.
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Background: There is scarce evidence on the rate of adverse events and the consequences on disease activity after vaccination against covid19 Objectives: To evaluate adverse events to vaccination and disease fares after vaccination in patients with axial spondyloarthritis (axSpA), peripheral spondy-loarthritis (pSpA) and psoriatic arthritis (PsA) and to evaluate factors associated with adverse event. Methods: Cross-sectional, observational, descriptive study. Consecutive patients with diagnosis of ankylosing spondylitis (AS) and non-radiographic axial spondy-loarthritis (nr-axSpA) according to ASAS 2009 criteria;pSpA according to ASAS 2011 criteria and PsA according to CASPAR criteria were included. Demographic data, disease clinimetry, treatments, vaccination received and post-vaccination adverse events were recorded. We evaluated, according to medical criteria, whether the patient presented a fare disease after vaccination and whether it was mild, moderate or severe. We also evaluated the factors associated with the presence of at least one mild adverse event. Statistical analysis: descriptive statistics were performed, qualitative variables were expressed as frequency and percentage (%), numerical variables as mean and standard deviation (SD) or median and percentile25-75. Binary logistic regression was performed using the presence of at least one mild adverse event to vaccination as the dependent variable. Results: 210 patients were included with a mean age of 45 (SD 15) years. The diagnoses were: AS 50 (23.8%), nr-axSpA 10 (4.8), pSpA 9 (4.3%), PsA 141 (67%) and time of disease evolution in months 109 (SD 96). Regarding comorbidities, the following frequencies were reported: arterial hypertension 60 (30%), diabetes mellitus 25 (12%), heart failure 4 (2%), asthma/EPOC 15 (7%), infammatory bowel disease 2 (1%), acute anterior uveitis 20 (9.5%), psoriasis 128 (61%). Sixteen percent (n=33) of the patients had SARS-CoV-2 infection prior to vaccination. Regarding treatments, those used were: antiTNF 88 (42%), Tofacitinib 6 (2.9%), Ustekinumab 2 (1%), Secukinumab 35 (17%), Ixekizumab 2 (1%), methotrexate 98 (47%), lefunomide 7 (3. 3), sulfasalazine 7 (3.3), apremilast 1 (0.5%), continuous NSAIDs 26 (12.4%) and NSAIDs on demand 103 (49%). Vaccines received were: Sputnik V 109 (51.9%), Oxford Vaccine, AstraZeneca 63 (30%), Janssen 1 (0.5%), BioNTech Vaccine, Pfzer 1 (0.5%), Sinopharm 33 (15.7%), Moderna 0%, Novavax 0% and others;3 (1.4%). Thirty-eight percent (n=80) of patients reported having mild post-vaccination symptoms, of which 3.75% did not resolve, 41% resolved with medication and 39% resolved ad integrum without medication. The presence of mild adverse event to the vaccine was associated with lower use of methotrexate (31% vs 56 %, p<0.001), and lower age (54 (SD 14) vs 47 (SD 12), p<0.001), and lower BMI (25 (24-30.5) vs 28 (25-31), p<0.001);while no association was found with sex, diagnosis, comorbidities, treatments, desease activity or vaccines. In the logistic regression analysis all the variables remained independently associated with a lower probability of presenting a mild adverse event: methotrexate: OR: 0.30, 95%CI 0.15-0.58, p<0.001, age: OR: 0.97, 95%CI 0.95-0.99, p: 0.03, BMI: OR: 0.92, 95%CI 0.95-0.99, p: 0.02. Sixty-one percent (n=129) of patients received the 2nd dose of vaccination, which 27% (n=35) presented mild adverse event and only 1 (0.8%) patient suffered post vaccination disease fare. Conclusion: Vaccination against COVID19 appears to be safe in this population, with only mild adverse events and low frequency of fare disease. Mild adverse events were associated with less use of methotrexate, younger age and lower BMI.
ABSTRACT
Background: It is assumed that patients with immuno-infammatory rheumatic diseases (IIRDs) in old age are susceptible to a more severe course of COVID-19 both due immunological disorders (autoimmune disease and its activity, immuno-suppressive therapy, immunosenescence leading to systemic subclinical chronic infammation with increased secretion of IL-6, IL-1, IL-18, TNF-α) and due to the presence of comorbid pathology. There are no Russian data on the course of COVID-19 in elderly patients with IIRDs. Objectives: To study the features of the course of COVID-19 in elderly patients with IIRDs. Methods: The study included 93 patients with IIRDs: 72 women, 21 men, average age 67.5±6.1 years. Of them, 62 patients suffered from rheumatoid arthritis, 9-systemic sclerosis, 5-ankylosing spondylitis, 4-Sjogren's disease, 4-systemic vasculitis, 3-psoriatic arthritis, 2-osteoarthritis, 1 systemic lupus erythematosus, 1-polymyositis, 1-rheumatic polymyal-gia, 1-gout. At the moment of COVID-19, 10 patients had high activity of IIRDs, 26-moderate, 40-low, 17-remission. 69 patients were treated with disease-modifying antirheumatic drugs-DMARDs (40-methotrexate, 12-lefunomide, 8-sulfasalazine, 7-hydroxychloroquine), 45-glucocorticoids (34-low doses, 11-medium or high doses). 36 patients received biologic or target DMARDs: 24-rituximab (the interval from the last administration to the development of COVID-19 symptoms averaged 7 months), 4-TNF-α inhibitors, 3-abatacept, 2-secukinumab, 1-tofacitinib, 1-baricitinib, 1 ustekinumab. Comorbidities included hypertension (n=74), coronary artery disease (n=27), obesity (n=17), diabetes mellitus (n=8), bronchial asthma (n=5), chronic obstructive pulmonary disease (n=4), chronic kidney disease (n=3). The patients were interviewed by a research doctor, additional information was obtained from medical documentation. Results: The most common symptoms of COVID-19 were fever-67.7%, weakness/drowsiness-53.7%, cough-48.4%, as well as anosmia and dyspnea-35.5% each, headache-20.4%, body aches-16.1%, congestion nose-8.6%, chest pain-7.5%, dysgeusia-5.4%, diarrhea/vomiting-3.2%. According to CT chest scan, 8 patients had 0% of lung damage, 31-25%, 32-50%, 12-75%, in other cases the study was not carried out (n=9) or data are not available (n=1). In 2 patients the course of COVID-19 was complicated by bacterial pneumonia, in 1-bacterial-fungal. An asymptomatic course was noted only in 2 patients (PCR+/IgM +, CT 0, close contact with a confrmed case of COVID-19). Recovery was noted in 90 patients, fatal outcome-in 3. Exacerbation of IIRDs after COVID-19 was noted in 48.4% of patients, which required intensifying antirheu-matic therapy. Conclusion: Preliminary data indicate that COVID-19 is characterized by moderate and severe course in elderly patients with IIRDs. Further studies are required to identify risk factors for severe course and complications in order to provide timely qualifed care.
ABSTRACT
Background: Patients with giant cell arteritis (GCA) represent a fragile population with an increased infection risk. In a recent study1 older age, a higher number of comorbidities, higher disease activity, and prednisolone ≥10 mg qd were associated with worse COVID-19 outcomes. Objectives: We aimed to evaluate the frequency and severity of COVID-19 in a well-defned GCA cohort. Methods: We reviewed medical records of histologically and/or by imaging proven GCA patients diagnosed between September 2011 and February 2020 at our secondary/tertiary center and followed during the COVID-19 pandemic between March 2020 and December 2021 (22 months). Descriptive statistics was used to analyze the studied population. Results: Of 314 GCA patients diagnosed for the frst time during a 102-month period, 49 patients died before March 2020. Of the remaining 265 patients (69.4% females), SARS-CoV-2 infection was proven by PCR test in 39 (14.7%) patients (74.2% females, mean (SD) age at infection 76.2 (±9.6 years), 13 (33.3%) with large vessel GCA and 16 with cranial limited GCA). At the time of SARS-Cov-2 infection GCA was in a stable remission in 38 patients (13 without therapy, 10 on steroids alone, 9 on lefunomide monotherapy, 6 on steroids plus lefunomide (10 or 20 mg qd), 1 on ustekinumab;mean prednisolone equivalent dose of 4.6 mg qd) and relapsed in one patient 6 weeks earlier (predni-solone 30 mg plus lefunomide). Data on clinical manifestations of COVID-19 were available for 33 (84.6%) patients and are presented in Table 1, part A. Twenty-nine/39 (74.4%) patients had mild COVID-19 and were symptomatically treated at home, while 10 patients had severe infection (defned as a need of hospitalization and/or death), and one of those patients died due to COVID-19. One patient developed a transient neurologic ischemic attack related to COVID-19. Table 1, part B shows differences in GCA demographic and treatment at the time of mild vs. severe infection. We found no differences in gender, age, GCA type and GCA treatment between those with mild vs. severe COVID. Three patients developed COVID-19 after receiving two doses of anti-COVID vaccine (1.4% breakthrough rate). Overall, of 257 GCA patients eligible for vaccination, 210 (81.7%) were vaccinated by the end of December 2021. Conclusion: A quarter of our GCA patients had severe COVID-19. Low doses of glucocorticoids and treatment with lefunomide were not associated with severe COVID-19 course in our cohort.
ABSTRACT
Background and aim: Dual Targeted Therapy (DTT) is a novel therapeutic strategy proposed for the management of patients with complex inflammatory bowel disease (IBD). Our aim was to evaluate the safety and effectiveness of this approach in a real-life setting Materials and methods: In this single centre retrospective cohort study, we collected data on IBD patients receiving DTT from 2017 to 2022. Baseline characteristics, clinical activity of intestinal and extraintestinal disease, C-reactive protein (CRP) levels, endoscopic assessment and adverse events (AEs) were recorded. Clinical remission, CRP normalization, endoscopic remission and occurrence of AEs were investigated at baseline and during follow up Results: Sixteen patients were identified;indications for DTT were: uncontrolled IBD (11 patients), uncontrolled extraintestinal manifestations (EIMs) (6 patients: 4 spondyloarthritis, 2 psoriatic disease). Patients received vedolizumab (VDZ, 14, 87.5%), ustekinumab (UST, 8, 50%), anti-TNFα (7, 43.8%), sekukinumab (2, 12.5%), tofacitinib (1, 6.3%). The most common combinations were: VDZ+UST (6 patients, 37.5%) and adalimumab+VDZ (3, 18.8%). At baseline, 15/16 (93.8%) and 4/6 (66.6%) patients had active intestinal and EI symptoms, respectively;14 (87.5%) patients had positive CRP and 5 (31.3%) were receiving oral steroids. Median follow-up duration on DTT was 15 months (IQR 11-22). Clinical intestinal remission was reported by 6/16 (37.5%) and 3/11 (27.3%) patients at 6 and 12 months, respectively. Clinical remission of EIMs was reported by 3/7 (42.9%) at 6 and 5/7 (71.4%) patients at 12 months, respectively. CRP normalization was observed in 3/16 (18.8%) and 6/11 (54.5%) patients at 6 and 12 months, respectively. 80% of patients on steroid therapy at baseline discontinued them within 6 months. Endoscopic assessments were available for 8 patients, with endoscopic remission in 2, endoscopic improvement in 3 and no improvement in 3. Four patients (25%) experienced an AE (1 COVID-19 and reactivation of perianal disease;1 mild pneumonitis and reactivation of perianal disease;1 drug-induced pneumonitis;1 arthralgia and COVID-19). Finally, 1 patient underwent colectomy due to uncontrolled disease. Three patients discontinued DTT: 2 because of treatment failure, 1 because of an AE (drug-induced pneumonitis) Conclusions: DTT can be considered a reasonably safe and effective treatment in complex IBD patients, either with uncontrolled intestinal inflammation or with concomitant EIMs, when other therapeutic options have failed