Non-biologic Therapy Research Articles

Impact of Non-Persistence on Healthcare Resource Utilization and Costs in Patients With Immune-Mediated Rheumatic Diseases Initiating Subcutaneous TNF-Alpha Inhibitors: A Before-and-After Study.

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are chronic progressive immune-mediated rheumatic diseases (IMRD) that can cause a progressive disability and joint deformation and thus can impact in healthcare resource utilization (HCRU) and costs. The main outcome of the study was to assess the effect of non-persistence to treatment with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) on HCRU costs in naïve patients with IMRD who started treatment with adalimumab, etanercept, golimumab or certolizumab pegol during 12 months after initiation of treatment. The impact of persistence and non-persistence of SC-TNFis on HCRU costs was compared between 12 months before and 12 months after initiating SC-TNFis. Persistence was defined as the duration of time from initiation to discontinuation of therapy. The study was conducted in an acute care teaching hospital in Barcelona, Spain. Data for the period between 2015 and 2018 were extracted from the hospital cost management control database. HCRU costs comprised outpatient care, outpatient specialized rheumatology care, in-patient care, emergency care, laboratory testing and other non-biological therapies. The study population included 110 naïve SC-TNFis patients, divided into the cohorts of persistent (n = 85) and non-persistent (n = 25) patients. Fifty-six percent of patients were women, with a mean (standard deviation) age of 47.6 (14.8) years. Baseline clinical features and HCRU costs over the 12 months before the index prescription were similar in the two study groups. Before-and-after differences in mean (standard deviation) HCRU costs were significantly higher in the non-persistence group as compared to the persistence group for outpatient rheumatology care (€110.90 [234.56] vs. €20.80 [129.59], p = 0.023), laboratory testing (−€193.99 [195.88] vs. −€241.3 [217.88], p = 0.025), other non-biological drugs (€3849.03 [4046.14] vs. −€10.90 [157.42], p < 0.001) and total costs (€3268.90 [4821.55] vs. −€334.67 (905.44), p < 0.001). Treatment persistence with SC-TNFis may be associated with HCRU cost savings in naïve IMRD patients. Prescribing SC-TNFis with the best long-term persistence is beneficial.

Abstract 9057: Anti-inflammatory Effect of Biologic Therapy in Patients With Psoriatic Disease: A Prospective Cohort Fdg-pet Study

Introduction: Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. Hypothesis: Central vascular inflammation (VI) as measured on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta will improve in patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and controls. We also postulate that in patients responding to biologics, there will be an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. Methods: We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and patients with non-inflammatory arthritis). The primary outcome of our study was the change in VI, estimated as the target-to-background ratio by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. Results: 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (change in TBRmax: -0.46±0.55) when compared to the the PsO group treated with non-biologic therapy (change in TBRmax: 0.23±0.67). The group with imaging evidence of a response to biologic agents (i.e. TBRmax drop greater than median value) maintained MFR (change in MFR of 0.05±0.19) when compared to the group with a response on TBRmax that was below the median, which had a drop in MFR (-2.9±0.8) (P=0.03). Conclusions: VI in the thoracic aorta decreased compared to psoriasis patients treated with non-systemic therapies and controls. Psoriasis patients treated with biologics who demonstrated a significant response on FDG PET imaging, maintained their MFR compared to non-responders. There is a positive impact of immune therapies on VI and microvascular disease in patients with chronic inflammation.

Real-World Incidence of Suboptimal Response to Anti-Tumor Necrosis Factor Therapy for Ulcerative Colitis: A Nationwide Population-Based Study.

Background/AimsAlthough anti-tumor necrosis factor (TNF) agents have been widely used to treat ulcerative colitis (UC), the real-world incidence of suboptimal response to anti-TNF agents has not been thoroughly investigated, especially among Asians.MethodsUsing the Korean National Health Insurance database, we collected data on UC patients who initiated anti-TNF agents between July 1, 2014, and June 30, 2017. We assessed suboptimal responses, including anti-TNF discontinuation or dose escalation, switching to other biologics, augmentation with a non-biologic therapy, and the requirement for colectomy.ResultsA total of 1,268 patients were included as new anti-TNF users (infliximab 713, adalimumab 433, golimumab 122). The proportion of patients who experienced at least one suboptimal response within 1 year among all patients was 63.5%, including 59.1%, 69.5%, and 68.0% of patients treated with infliximab, adalimumab, and golimumab, respectively. The cumulative incidences of at least one suboptimal response over time were 41.5%, 63.7%, 80.5%, and 87.1% at 6, 12, 24, and 36 months, respectively. Cox proportional hazards modeling revealed that adalimumab was associated with a higher risk of at least one suboptimal response (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.13 to 1.48), dose escalation (HR, 4.35; 95% CI, 2.97 to 6.38) and discontinuation (HR, 1.25; 95% CI, 1.03 to 1.52) than infliximab. Golimumab was associated with a higher risk of switching to other biologics than infliximab (HR, 1.78; 95% CI, 1.21 to 2.60).ConclusionsMore than half of Korean UC patients had suboptimal responses to anti-TNF agents within 1 year. UC patients treated with infliximab might be less prone to suboptimal responses than those treated with adalimumab or golimumab.

Management of pediatric generalized pustular psoriasis using biologics: An evidence-based review

Management of pediatric generalized pustular psoriasis using biologics: An evidence-based review

Risk of herpes zoster associated with biological therapies for psoriasis and psoriatic arthritis: A systematic review and meta-analysis.

Background:Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common.Objective:To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy.Data sources:A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment.Study eligibility criteria:The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0).Results:The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18–1.86; I2 = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02–1.71; I2 = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11–2.02; I2 = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31–4.50; I2 = 0%) and etanercept (OR: 1.65; 95% CI: 1.07–2.56; I2 = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64–2.30; I2 = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89–5.44; I2 = 0%), alefacept (OR: 1.46; 95% CI: 0.20–10.47; I2 = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22–11.34; I2 = 0%) did not.Limitations:Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs.Conclusions and implications of key findings:Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors.Systematic review registration number:INPLASY202110027.

ANTI-INFLAMMATORY EFFECT OF BIOLOGIC THERAPY IN PATIENTS WITH PSORIATIC DISEASE COMPARED WITH TREATMENT WITH NON-BIOLOGIC DMARDS: A PROSPECTIVE COHORT FDG-PET STUDY

<h3>BACKGROUND</h3> Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. We hypothesized that central vascular inflammation on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta would improve in these patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and non-inflammatory control patients. We also postulated that in patients responding to biologics, there would an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. <h3>METHODS AND RESULTS</h3> We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and control patients with non-inflammatory arthritis). The primary outcome of our study was the change in vascular inflammation, estimated as the target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. A total of 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). The majority (64.7%) of participants were men and the median age was 62 years (IQR: 48, 69). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (thoracic aorta change in TBRmax: -0.46±0.55) when compared to the change in the thoracic aorta FDG uptake of the PsO group treated with non-biologic therapy (thoracic aorta change in TBRmax: 0.23±0.67). Furthermore, the group with imaging evidence of a response to biologic agents (i.e. TBRmax drop > median value of 7%) maintained MFR (3.40±1.23 MFR to 3.5±1.2 MFR over 6 months) when compared to the group with a below median response on TBRmax which had a drop in MFR (2.9±0.8 MFR to 2.2±0.6 over 6 months) (P=0.03). <h3>CONCLUSION</h3> In a cohort of psoriasis patients treated with biologics, the FDG uptake in the thoracic aorta decreased over the study period compared to psoriasis patients treated with non-systemic therapies as well as controls. Additionally, psoriasis patients treated with biologics who demonstrated a significant anti-inflammatory response on FDG PET imaging, maintained their MFR compared to non-responders. This study supports the notion that there is a positive impact of immune therapies on vascular inflammation and microvascular disease in patients with chronic inflammation.

Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study

BackgroundIn SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of...

Incidence and prevalence of psoriatic arthritis in patients with psoriasis stratified by psoriasis disease severity: Retrospective analysis of an electronic health records database in the United States

Among patients in the United States with psoriasis (PsO), limited data exist on the incidence and prevalence of psoriatic arthritis (PsA) based on disease severity. To assess the incidence, prevalence, and predictors of PsA among patients with PsO stratified by PsO severity using treatment type. Incidence of PsA per 100 PsO patient-years (PY) and prevalence were assessed using the Optum electronic health records database. Incidence was assessed from PsO diagnosis and 1year after PsO diagnosis overall and stratified by mutually exclusive treatment classes as a severity surrogate. The overall incidence of PsA was 2.9 (95% CI, 2.9-3.0) events per 100 PY. The incidence (95% CI) by severity surrogate was 2.1 (2.1-2.1), 9.9 (9.5-10.4), and 17.6 (16.9-18.3) events per 100 PY for patients with mild, moderate, and severe PsO as determined by receiving nonsystemics, nonbiologic systemic therapy, and biologics, respectively. When excluding patients diagnosed with PsA 1year after PsO diagnosis, overall incidence was lower (1.7 [95% CI, 1.6-1.7] events per 100 PY), with similar trends for treatment-severity surrogates. Results may not be generalizable to a wider population. The risk of developing PsA increased with disease severity and was highest in patients with the most severe PsO.

Biologic therapy is not associated with increased COVID-19 severity in patients with hidradenitis suppurativa: Initial findings from the Global Hidradenitis Suppurativa COVID-19 Registry

Biologic therapy is not associated with increased COVID-19 severity in patients with hidradenitis suppurativa: Initial findings from the Global Hidradenitis Suppurativa COVID-19 Registry

Beyond-Mild Psoriasis: A Consensus Statement on Calcipotriol and Betamethasone Dipropionate Foam for the Topical Treatment of Adult Patients

IntroductionThere are clear treatment options for mild psoriasis where topical therapies are the mainstay, and for severe psoriasis where systemic therapy (biologic or non-biologic) is necessary. However, there is less clarity in the ‘grey zone’ of patients in the moderate or so-called ‘beyond-mild’ segment. There are frequent delays to the initiation, discontinuation, switching and dose change in treatment, and many patients fail to continue treatment because of concerns about safety or lack of efficacy. Treatment with topical therapies, such as calcipotriol and betamethasone dipropionate (Cal/BD) combinations, may be suitable for these patients.MethodThese consensus recommendations on the use of topical therapies including Cal/BD foam for beyond-mild psoriasis originated from a modified Delphi process of European clinical experts. In the process, the experts iteratively refined a series of draft statements, which had to receive ≥ 80% approval to be incorporated into the consensus.ResultsThe experts identified three main themes: Cal/BD foam as monotherapy, as an add-on to non-biologic systemic therapies and as an add-on to systemic biologics. The consensus emphasises disease factors and patient preference in treatment choice, summarises the evidence base for Cal/BD foam monotherapy for flare treatment as well as long-term management, and identifies the potential for improved treatment outcomes, such as reduced time to onset of action and reduced systemic dose to minimise side effects for add-on Cal/BD therapy to non-biologic systemics. The recommendations regarding add-on Cal/BD foam to biologics are similar to those for non-biologic systemic therapies, but also include suggestions for patients on biologics who are late responders. As clinical choices of Cal/BD combination vary, we have here often used ‘Cal/BD’ without reference to any particular formulation.ConclusionsThese recommendations aim to give practical guidance to those treating patients with beyond-mild psoriasis, to support patients’ use of topical preparations and to optimise treatment outcomes.

Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conventional synthetic disease-modifying antirheumatic drug therapy and enrolled in a North American clinical registry

BackgroundUnderstanding the evolving treatment patterns in patients with rheumatoid arthritis (RA) is important for rheumatologists to make the best practice decisions and optimize treatment. Here, we describe treatment patterns among patients newly initiated on biologic and/or nonbiologic RA therapy over time after enrollment in the US Corrona RA registry.MethodsThis was a retrospective, cohort study of adult patients with RA enrolled in the Corrona RA registry. Patients were included in this study if they initiated therapy with conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, TNF inhibitor (TNFi) monotherapy, other (non-TNFi) biologic monotherapy, or combination therapy (index therapy); initiated therapy between January 1, 2004, and December 31, 2015 (index date), after enrollment in the Corrona RA registry; had at least 6 months of follow-up time after the index date; and had at least one follow-up visit. Time periods of interest were based on the year of index therapy initiation: 2004–2007, 2008–2011, and 2012–2015.ResultsThis study included 8027 patients. csDMARD monotherapy and TNFi + csDMARD combination therapy were the most common index therapies in the registry (39.9% and 44.9%, respectively, in the 2004–2007 period; 38.6% and 38.2%, respectively, in the 2008–2011 period; and 35.2% for both in the 2012–2015 period). At therapy initiation, a higher proportion of patients who initiated other biologics, whether as monotherapies (54.0%) or in combination with csDMARD (49.9%), had high disease activity than those who initiated csDMARD monotherapy (28.4%). For 2012–2015 vs 2004–2007 and 2008–2011 periods, persistence on a given therapy appeared to decrease for the TNFi monotherapy cohort (48.2% vs 64.3% and 52.4%) and other biologic monotherapy cohort (52.3% vs 71.4% and 54.5%) over 12 months; switching from one therapy to another was common in the Corrona RA registry.ConclusionsIncreased switching from one therapy to another and decreased time on a given therapy was observed in the Corrona RA registry in the 2012–2015 period. This observation is most likely due to the increased availability of additional treatment options and/or the change in clinical focus, particularly the emphasis on achievement of treat-to-target goals of remission or low disease activity along with more aggressive treatment.

Association between vedolizumab and postoperative complications in IBD: a systematic review and meta-analysis.

The effect of preoperative vedolizumab (VDZ) therapy on postoperative complications in inflammatory bowel disease (IBD) patients is still controversial. This meta-analysis aims to review postoperative complications of IBD patients who preoperatively received VDZ. A meta-analysis of the available literature was performed. Studies of IBD patients who received VDZ and non-VDZ therapy (including anti-TNF-α agents, non-biological therapy, other biological agents, ustekinumab, and placebo) before surgery were included. Primary outcomes included overall complications, infectious complications, and non-infectious complications. Twelve studies with 1925 IBD patients were enrolled, among which 709 patients received VDZ treatment. The results show that, compared with non-VDZ treatment, there is no significant difference in the incidence of overall complications (OR = 1.25, p = 0.43) for adult IBD patients treated with VDZ preoperatively, the incidence of infectious complications (OR = 0.49, p = 0.001) decreases, but the risks of all surgical site infection (SSI) (Crohn's disease (CD): OR = 2.97, p < 0.001), superficial surgical site infection (sSSI) (OR = 2.24, p = 0.02), and ileus (OR = 2.16, p < 0.001) increase. The risk of mucocutaneous separation (MCS) (OR = 4.69, p = 0.03) with VDZ is also higher than non-VDZ. Two studies involved pediatric patients and showed no difference in ileus (OR = 0.55, p = 0.55). Overall, compared with non-VDZ treatment, preoperative use of VDZ is relatively safer in adult IBD patients, which does not increase the risk of overall postoperative complications and reduces the occurrence of infectious complications. But, it increases the risk of all SSI and sSSI in infectious complications and the incidence of ileus and MCS in non-infectious complications. Due to lack of sufficient data, the safety of VDZ in pediatric patients is uncertain and requires further study.

Histological Hallmarks of Mucosal Healing in Inflammatory Bowel Diseases in the Era of Monoclonal Antibodies Therapy: New Insights and Perspectives

Background: Chronic inflammatory bowel diseases (IBDs) are gaining increasing attention, both because they can severely reduce the quantity and quality of life, and because the advent of monoclonal antibodies has profoundly changed the natural history of these diseases. In recent years, the concept of mucosal healing has assumed a certain importance, and there are more and more clinical and pharmacological trials that consider this parameter among their endpoints, so much so that it may soon be included among the desirable clinical outcomes of patients with IBD. Methods: We performed a literature review of the Pubmed, Medline, and Web of Science (WoS) databases. Results: We selected 88 articles and then removed 6 duplicates; the final sample after accurate application of the inclusion criteria numbered 73 articles, with a level of evidence rating of three or four, according to Oxfords Evidence-based medicine. Our aim was to study the histological impact of monoclonal antibody therapies on mucosal healing, taking into consideration the few studies present in the literature. To perform this review, we compared studies that examined patients with Crohn’s disease (CD) and/or ulcerative colitis (UC) undergoing monoclonal therapy versus patients undergoing other non-biological therapies (PICO statements). Conclusions: We try to delineate how monoclonal antibodies have changed the natural history of IBD, acting at the microscopic level, and we believe that a careful analysis of the histopathology and the definition of the objective criteria for “Mucosa Healing” should enable this concept to be included among the clinical endpoints of patients affected by IBD, thus contributing to a better therapeutic management of these patients.

Sequences of biological treatments for patients with moderate-to-severe rheumatoid arthritis in the era of treat-to-target in China: a cost-effectiveness analysis.

Biologic disease-modifying antirheumatic drugs (bDMARDs) are recommended to be added in sequentially in the treatment of moderate-to-severe rheumatoid arthritis (RA). All these drugs, however, are substantially more expensive than conventional synthetic DMARDs throughout the world, including in China. The objective of this study is to evaluate the cost-effectiveness of treatment sequences of bDMARDs for patients with moderate-to-severe rheumatoid arthritis from the Chinese healthcare system perspective. An individual patient simulation model was used to track the course of patients from first treatment through switches to further lines in a sequence. The comparator treatment sequence commenced with methotrexate, followed by non-biologic therapy. The intervention sequences were assumed to be the combinations of bDMARDs available, followed by non-biologic therapy. Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated. Univariable and probabilistic sensitivity analyses and scenario analyses were performed to evaluate the model uncertainty. Compared with the comparator treatment sequence, bDMARDs sequences were associated with more life years, QALYs, and cost. These produced ICERs ranged from $27,441.36/QALY to $40,149.2/QALY, above the willingness-to-pay threshold of $10,378 per QALY. The uncertainty analyses and the scenario analyses confirmed the result of the base case analysis. From the perspective of the Chinese healthcare system, bDMARDs sequences are estimated not to be cost-effective compared with conventional synthetic disease-modifying antirheumatic drug strategy for patients with moderate-to-severe RA at a WTP threshold of $10,378 per QALY. Price reductions are warranted to make bDMARDs cost-effective and affordable.

BIOLOGICAL TREATMENT OF PSORIASIS IN TIME OF NEW CORONAVIRUS INFECTION COVID-19

Currently, the ongoing pandemic of the novel coronavirus infection is still a major public health problem worldwide. The questions of immunosuppressive therapy of patients with psoriasis and psoriatic arthritis, the possibility of vaccination against the background of the use of genetically engineered drugs remain open. The article is of an overview nature and includes up-to-date information on the feasibility and safety of the use of genetically engineered biological drugs in patients with psoriasis in a pandemic (COVID-19). According to the international recommendations of the National Psoriasis Foundation COVID-19 Task Force expert group, treatment of psoriasis and/or PsA does not significantly alter the risk of SARS-CoV-2 infection and does not lead to worse prognosis of COVID-19. Therefore, patients not infected with SARS-CoV-2 should continue biological or other systemic therapy for psoriasis and/or PsA. According to a registry from 25 countries, hospitalization with SARS-CoV-2 infection was more common in patients receiving nonbiological systemic therapy than in patients receiving BAs. Thus, genetically engineered biological drugs do not appear to cause an increased risk of coronavirus infection and do not determine a more severe course. With regard to vaccination of patients with psoriasis, many issues require further study. According to international agreements, vaccination is not contraindicated in patients with psoriatic disease. However, there is still insufficient data on how the treatment of psoriatic disease affects vaccination. Avoiding COVID-19 or reducing the severity of infection following SARS-CoV-2 vaccination is thought to far outweigh any risk directly related to vaccination complications.

Lower incidence of COVID-19 in patients with inflammatory bowel disease treated with non-gut selective biologic therapy.

Background and AimSince the outbreak of COVID‐19, concerns have been raised as to whether inflammatory bowel disease (IBD) patients under biologic therapy may be more susceptible to the disease. This study aimed to determine the incidence and outcomes of COVID‐19 in a large cohort of IBD patients on biologic therapy.MethodsThis observational retrospective multicenter study collected data about COVID‐19 in IBD patients on biologic therapy in Italy, between February and May 2020. The main end‐points were (i) to assess both the cumulative incidence and clinical outcome of COVID‐19, according to different biologic agents and (ii) to compare them with the general population and a cohort IBD patients undergoing non‐biologic therapies.ResultsAmong 1816 IBD patients, the cumulative incidence of COVID‐19 was 3.9 per 1000 (7/1816) with a 57% hospitalization rate and a 29% case‐fatality rate. The class of biologic agents was the only risk factor of developing COVID‐19 (P = 0.01). Non‐gut selective agents were associated with a lower incidence of COVID‐19 cases, related symptoms, and hospitalization (P < 0.05). Compared with the general population of Lombardy, an overall lower incidence of COVID‐19 was observed (3.9 vs 8.5 per 1000, P = 0.03). Compared with 565 IBD patients on non‐biologic therapies, a lower rate of COVID‐19 symptoms was observed in our cohort (7.5% vs 18%, P < 0.001).ConclusionsCompared with the general population, IBD patients on biologic therapy are not exposed to a higher risk of COVID‐19. Non‐gut selective agents are associated with a lower incidence of symptomatic disease, supporting the decision of maintaining the ongoing treatment.

P612 Lower incidence of COVID-19 in patients with Inflammatory Bowel Diseases treated with non-gut-selective biologic therapy: an observational multicentre study

BackgroundSince the outbreak of COVID-19, concerns have been raised as to whether IBD patients under biologic therapy might be more susceptible to the disease and its complications. This study aimed to determine the incidence and outcomes of COVID-19 in a large cohort of IBD patients on biologic therapy in Lombardy, the hardest-hit Italian region by the pandemic.MethodsThis is an observational retrospective multicentre study collecting data about COVID-19 in IBD patients on biologic therapy in regular clinical follow-up at 11 IBD referral units in Lombardy, between February 20th and May 20th, 2020. The main endpoints were to assess the cumulative incidence of COVID-19 and its outcome (hospitalization/death) among IBD patients on biologic therapy and to identify any variations among the different classes of biologic agents. Secondarily, we compared the results with the incidence of COVID-19 in the general population of Lombardy in the same period and the incidence of symptoms suggestive of COVID-19 in our study population compared with those of a second cohort of IBD patients undergoing non-biological therapies and coming from the same geographic area.ResultsOverall, 1816 IBD patients on biologic therapy were enrolled. The cumulative incidence of COVID-19 was 3.9 per 1000 (7/1816) with a hospitalization rate of 57% and a case-fatality rate (CFR) of 29%. In our Cohort, the gut-selective therapy (Vedolizumab and Etrolizumab) was the only risk factor of developing symptomatic COVID-19 (OR 8.7, 95% CI 1.7–45.0, p = 0.01). Conversely, non-gut selective anti-cytokine agents were associated with a lower incidence of infection (OR 0.13, 95%CI 0.02–0.74) and development of symptoms (OR 0.60, 95%CI 0.37–0.98). Compared to the general population of Lombardy, a lower incidence of COVID-19 was observed (3.9 vs 8.5 per 1000 with a RR 0.45, 95%CI 0.21–0.95); conversely, in terms of hospitalization rate and CFR, the clinical outcome was not statistically different. Finally, compared to a second cohort of 565 IBD patients treated with non-biologic conventional therapies, a significantly lower risk of symptomatic disease was observed in patients on biologic agents (OR 0.3, 95%CI 0.2–0.4, p<0.01).ConclusionCompared to the general population, IBD patients on biologic therapy are not exposed to a higher risk of COVID-19; compared to gut-selective agents, cytokine blockers are associated with a lower incidence of symptomatic infection, supporting the decision of maintaining the ongoing treatment.

P207 Clinical outcome of patients with Ulcerative colitis after anti-TNF discontinuation -\t10 years follow up

Abstract Background Biological therapy for ulcerative colitis (UC) such as anti-TNF have shown high efficacy in achieving remission. There is a lack of information about the long-term outcomes after biologic withdrawal and validated clinical, immunologic, genetic or laboratory markers that can predict outcome after withdrawal accurately. The aims of this study were to describe the long-term outcomes after anti-TNF withdrawal and discover potential biomarkers to predict long-term remission as an approach to towards personalized medicine. Methods 75 patients with moderate to severe UC treated to remission with anti-TNF were included in the study. These patients were categorized as either “Long term remission” (LTR) or “Relapse”. The “Relapse” group were divided in subgroups by the highest treatment level needed to obtain remission the last 3 years of observation: non-biological therapy, biological therapy or colectomy. LTR were divided in LTR + immunomodulating (imids) drugs and a new clinical phenotype “Near the Cure of disease” (NCD), defined as &amp;gt; 3 years in remission with no medication or 5ASA only. Results The median (IQR) observation time of all patients included were 121(111–137) months. Of the 75 patients 46 (61%) did not receive biological therapy including 23 (31%) in LTR + imids. Of the 23 patients 16 were defined as NCD with an observation time of median (IQR) 95(77–113) months. Fourteen patients underwent colectomy and 15 patients received biological therapy the last 3 years of the follow-up. Mucosal TNF copies/µg mRNA &amp;lt; 10 000 at anti-TNF discontinuation predicted long-term remission, biological free remission and lower risk of colectomy with a HR 0.36 (0.14–0.92) for long term remission, HR 0.17 (0.04–0.78) for biological free remission and HR 0.12 (0.01–0.91) for coelctomy. Conclusion This 10-year anti-TNF discontinuation follow up study of UC shows that 61% of patients experience an altered phenotype to a milder disease course without need of biological therapy. Normalized mucosal TNF transcript predict this mild disease course and lower risk of colectomy. Of special interest is that 21% of the patients defined as “Near the cure of disease” were in long-term remission without any medication or receiving 5ASA only.

P340 Real-world treatment patterns and recurrence rates of rectovaginal fistulas in patients with Crohn’s disease: A retrospective cohort database analysis

Abstract Background Rectovaginal fistulas (RVF) are a difficult to treat perianal complication of Crohn’s disease (CD) with a significant impact on quality of life. Management of RVF includes both medical and surgical interventions. Few studies have assessed real-world treatment patterns for CD-related RVF. This retrospective US cohort database analysis aimed to assess the rate of, and time to RVF episodes of care in CD, and describe treatment patterns. Methods IBM Truven Health MarketScan® databases (Commercial and Medicare supplemental administrative claims [01/01/01 to 31/12/19]) were used. Adult females with a diagnosis code for CD, ≥1 medical claim with a RVF-specific diagnosis/procedure ICD-9/10 code on or after the date of first observed CD diagnosis, and ≥180 and ≥720 days of continuous health plan enrolment before and after index (date of first RVF-related code after first CD diagnosis date), respectively, were included. Treatment patterns were assessed during the 6 months pre-index (baseline period) and any time post-index. The first RVF episode of care (episode) started on the date of the first RVF-related code after CD diagnosis. RVF-related codes ≤90 days apart were considered as the same episode. Time to subsequent episodes was assessed by Kaplan–Meier (KM) analysis. Only descriptive statistics were reported for the proportion of patients with episodes and subsequent treatment patterns. Results Of 274 096 adult females diagnosed with CD during a continuous eligibility period, 2540 (0.9%) had a RVF-specific code. Overall, 963 patients met the inclusion criteria (median age: 46.0 years). The median follow-up (time between the index date and end of continuous health plan enrolment or data availability) was 48.5 months. During the follow-up period, 963 (100%), 430 (44.7%) and 217 (22.5%) patients had at least one, two or three episodes, respectively. KM analysis showed the probability of having a subsequent episode within 1, 2 and 5 years of their first or second episode (Figure). During the baseline period, 775 (80.5%) and 287 (29.8%) patients received non-biologic or biologic therapies, respectively, and 929 (96.5%) and 494 (51.3%) at any time post-index. At any time post-index, 587 (61.0%) patients had ≥1 RVF-related surgery. Conclusion This study showed patients with CD-related RVF required recurrent episodes of medical and surgical care in a US real-world setting. In addition, post-index, an important proportion of patients were observed with biologics use (&amp;gt;50%) and nearly two-thirds of patients had RVF-related surgery. Patients with CD-related RVF had varied treatment patterns and more studies are needed to inform the standard of care for patients with RVF. Sponsor: Takeda Pharmaceuticals, Inc.

Risks of basal cell and squamous cell carcinoma in psoriasis patients after treatment with biologic vs non‐biologic systemic therapies

There are concerns that immunomodulatory therapies may increase the risks of developing basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) in patients with moderate-severe psoriasis. A systematic review showed that psoriasis patients were significantly more likely to develop SCC than the general population, though included studies lacked adequate comparator cohorts and adjustment for relevant confounding factors including heterogeneity between BCC and SCC in association with phototherapy and immunomodulatory therapies and lacked data on newer biologic therapies. We therefore followed-up a large prospective patient cohort to determine whether the risks of developing BCC and SCC are increased in patients with psoriasis receiving biologic therapy compared with those treated with non-biologic systemic therapies only.