anti-TNF Use Research Articles

S3909 Paradoxical Psoriasis and Alopecia Areata After the Use of Anti-TNF in a Patient With Crohn's Cisease

S3909 Paradoxical Psoriasis and Alopecia Areata After the Use of Anti-TNF in a Patient With Crohn's Cisease

Risk Factors for the Development of and Outcomes After Diagnosis of Autoimmune Alopecia Areata in Patients with Inflammatory Bowel Diseases.

The development of certain immune-mediated diseases (IMD) in patients with inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis (UC)] has been linked to treatment of IBD. Hair loss in some patients may be due to immune-mediated alopecia areata (AA). Risk factors and outcomes of AA in patients with IBD have not been previously explored. This was a retrospective, multi-center case-control study. Cases were identified as individuals who developed IBD before AA diagnosis. Controls comprised of those who were never diagnosed with AA and treated contemporaneously, selected using random number generator. We extracted demographic and IBD treatment history. Severity of Alopecia Tool (SALT) was used to stratify AA severity. AA outcomes and interventions were compared within controls. We identified 58 cases and 90 controls. Cases had significantly higher rate of tumor necrosis factor α antagonist (anti-TNF) use compared to controls (40.7% vs. 20.0%, p = 0.006). Both groups had similar IBD disease location, behavior, and related surgery. Majority of cases had endoscopic remission or mild disease activity at AA diagnosis. There was no difference in partial or complete improvement of AA between those who stopped or continued IBD therapy (p = 0.57). Those with severe AA were significantly less likely to have complete (0% vs 33.3%, p = 0.01) or any improvement (50% vs 84.9%, p = 0.02) of AA compared to those with non-severe AA. Individuals with IBD who later develop AA were more likely to have been on anti-TNF at time of AA onset. Severity of AA was a significant predictor of AA resolution. Fortunately many patients had improvement in their AA despite continuation of IBD therapy.

Prevalence and Factors Associated with De-escalation of Anti-TNFs in Older Adults with Rheumatoid Arthritis: A Medicare Claims-Based Observational Study.

The aim was to evaluate prevalence and factors associated with anti-tumor necrosis factor (anti-TNF) de-escalation in older adults with rheumatoid arthritis (RA). We identified adults ≥66 years of age with RA on anti-TNF therapy within 6 months after RA diagnosis with at least 6-7 months duration of use (proxy for stable use), using 20% Medicare data from 2008-2017. Patient demographic and clinical characteristics, including concomitant use of glucocorticoid (GC), were collected. Anti-TNF use was categorized as either de-escalation (identified by dosing interval increase, dose reduction, or cessation of use) or continuation. We used (1) an observational cohort design with Cox regression to assess patient characteristics associated with de-escalation and (2) a case-control design with propensity score-adjusted logistic regression to assess the association of de-escalation with different clinical conditions and concomitant medication use. We identified 5106 Medicare beneficiaries with RA on anti-TNF, 65.5% of whom had de-escalation. De-escalation was more likely with older age (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.01-1.02) or greater comorbidity (HR 1.07, 95% CI 1.05-1.09), but was less likely with low-income subsidy status (HR 0.85, 95% CI 0.78-0.92), adjusting for patient sex and race/ethnicity. Lower odds of de-escalation were associated with serious infection (odds ratio [OR] 0.79, 95% CI 0.66-0.94), new heart failure diagnosis (OR 0.70, 95% CI 0.52-0.95), and long-term GC use (OR 0.84, 95% CI 0.74-0.95), whereas higher odds were associated with concomitant methotrexate use (OR 1.16, 95% CI 1.03-1.31). Anti-TNFs are de-escalated in two-thirds of older adults with RA in usual care. Further study is needed on RA outcomes after anti-TNF de-escalation.

Trends in Targeted Therapy Usage in Inflammatory Bowel Disease: TRENDY Study of ENEIDA.

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Multiple Sclerosis Risk Among Anti-tumor Necrosis Factor Alpha Users: A Methodological Review of Observational Studies Based on Real-world Data.

Epidemiologic studies on the risk of multiple sclerosis (MS) or demyelinating events associated with anti-tumor necrosis factor alpha (TNFα) use among patients with rheumatic diseases or inflammatory bowel diseases have shown conflicting results. Causal directed acyclic graphs (cDAGs) are useful tools for understanding the differing results and identifying the structure of potential contributing biases. Most of the available literature on cDAGs uses language that might be unfamiliar to clinicians. This article demonstrates how cDAGs can be used to determine whether there is a confounder, a mediator or collider-stratification bias and when to adjust for them appropriately. We also use a case study to show how to control for potential biases by drawing a cDAG depicting anti-TNFα use and its potential to contribute to MS onset. Finally, we describe potential biases that might have led to contradictory results in previous studies that examined the effect of anti-TNFα and MS, including confounding, confounding by contraindication, and bias due to measurement error. Clinicians and researchers should be cognizant of confounding, confounding by contraindication, and bias due to measurement error when reviewing future studies on the risk of MS or demyelinating events associated with anti-TNFα use. cDAGs are a useful tool for selecting variables and identifying the structure of different biases that can affect the validity of observational studies.

Adalimumab (ADA) in Pediatric Non-infectious Uveitis: An Observational Study.

Pediatric uveitis is a rare but sight-threatening condition. Prompt and adequate treatment is crucial to preserve vision and avoid long-term complications. In cases that are resistant to corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs), anti-tumor necrosis (anti-TNF) biologic agents are usually added. In this study, we report our experience with adalimumab (ADA) anti-TNF use in this group of patients. This is a retrospective observational study conducted in a tertiary pediatric uveitis clinic, in Manchester Royal Eye Hospital. All patients were pediatric patients (aged 2-18 years old) under follow-up during the period of six months. The patients' data were analyzed according to the diagnosis, age of onset of uveitis, systemic medications used before and concomitantly withADA, duration of uveitis before starting ADA, its effect, and time to notice the therapeutic effect in controlling inflammation. Finally, cases were reviewed for the development of anti-drug antibodies. Forty-two patients were included in the study. Idiopathic uveitis was diagnosed in 47.6% of patients and 40.5% of patients were associated with juvenile idiopathic arthritis (JIA). Most (97.6%) of patients were using topical steroids before starting ADA and 95.2% continued using steroids after established ADA use, but systemic steroid use was reduced from 33.3% to 14.3%. The most common non-biologic DMARD used before ADA was methotrexate (MTX) (90.5%). One-third of the patients started ADA between 6 and 12 months after the diagnosis of uveitis, while this percentage dropped to 9.5% the year after diagnosis. Seventy-eight percent of patients acquired complete clinical control of inflammation on ADA use. Almost 78.6% of patients showed a full response in less than six months. In eight patients who were not controlled or were transiently controlled on ADA, three patients had positive anti-drug antibodies. In one patient, antidrug antibodies were identified after 12 years of ADA use, and in another, after 4 years. Adalimumab is an effective, well-tolerated drug in children with uveitis refractory to non-biologic DMARD therapy. DMARDs were usually used alongside ADA in this cohort and few patients had confirmed ADA antibodies.

Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease?

ObjectiveIn this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment. MethodsThe study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study. ResultsOf the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04–67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months. ConclusionOur study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings.

Biological Agents in the Treatment of Crohn's Disease: A Propensity Score-Matched Analysis From the Prospective Persistence Australian National IBD Cohort (PANIC3) Study.

Comparative effectiveness research provides data on the relative benefits and risks between treatments. In Crohn's disease (CD), however, there are few head-to-head studies comparing advanced therapies and none with long-term follow-up. Real-world effectiveness, defined by treatment persistence, obtained from prospective population-based patient cohorts, may help determine the best sequencing and positioning of biological agents. We analyzed the prospectively collected population-based Australian national Pharmaceutical Benefits Scheme dispensing data registry (2005-2019) for CD. There is no mandated biological agent prescribing order, and all citizens and permanent residents are eligible for treatment irrespective of insurance status. Propensity score matching was performed to reduce selection bias. There were 2,029 lines of therapy in 1,446 patients (median age 43 years, interquartile range 34-58, 44% male patients) over the 15-year period with 5,618 patient-years of follow-up. Per line of therapy, 915/2,029 (45.1%) patients used adalimumab, 722/2,029 (35.6%) used infliximab, 155/2,029 (7.6%) used vedolizumab, and 237/2,029 (11.7%) used ustekinumab. When used in biological agent-naive patients, there was no difference in persistence between any agent ( P > 0.05). Used after first line in biological agent-experienced CD, ustekinumab had significantly better persistence than non-ustekinumab biological agents ( P = 0.0018), vs anti-tumor necrosis factor (TNF) alpha therapy ( P = 0.006) or vedolizumab ( P < 0.001). Ustekinumab persistence was unaffected by prior biological agent exposure ( P = 0.51). After anti-TNF use, ustekinumab had superior persistence to an alternative anti-TNF agent ( P = 0.033) and to vedolizumab ( P = 0.026). Using a propensity score-matched analysis adjusted for age, immunomodulator use, and bio-exposed status, ustekinumab had superior persistence to anti-TNF ( P = 0.01). Multivariate predictors of worse persistence were the use of a non-ustekinumab biological agent (adjusted hazard ratio 2.10, P < 0.001), and bio-experienced status (adjusted hazard ratio 1.23, P < 0.001). This large national prospective database with nonhierarchical prescribing of biological agents did not identify superior persistence of any agent in bio-naive CD. However, for patients with bio-experienced CD, persistence was greater with ustekinumab.

EARLY TUMOR NECROSIS FACTOR ANTAGONIST TREATMENT PREVENTS PERIANAL FISTULA IN PEDIATRIC CROHN’S DISEASE

Abstract BACKGROUND Perianal fistulizing complications (PFCs) develop amongst approximately 1/3 of children with Crohn’s disease (CD), are difficult to treat, and commonly recur. Recent retrospective studies suggested PFCs may be preventable with early therapy. We aimed to evaluate PFC prevention in a prospective cohort. Based on prior work, we hypothesized early tumor necrosis antagonist (anti-TNF) treatment would be associated with reduced risk of PFC development. METHODS The RISK cohort prospectively enrolled children (&amp;lt;18 yr) newly diagnosed with CD from 28 sites in North America (2008-2012). We obtained data from the Crohn’s &amp; Colitis Foundation’s IBD Plexus program. PFCs were defined as perianal fistula and/or abscess. Patients with PFCs at or before enrollment were excluded. Non-penetrating perianal lesions such as skin tags and fissures were collectively considered “perianal lesions”. We evaluated treatment from enrollment until 1mo prior to PFC development or end of enrollment. Treatment was categorized into 3 mutually exclusive groups: 1) No immunosuppression; 2) Immunomodulators (IM, thiopurines and/or methotrexate) but no anti-TNF; and 3) Anti-TNF (regardless of IM). Steroids were considered separately. We performed nearest neighbor propensity score trio matching, matching patients across treatment categories on gender, age at diagnosis, growth delay, deep endoscopic ulcers, small bowel involvement, and colonic involvement. Using matched samples, we evaluated the predicted probability of PFC development first by treatment group, then by time to follow up of the medication initiation after studying into 6-time intervals to maximum 3yr. Logistic regression analyses were used to estimate the odds ratios (OR) for PFC development. RESULTS In total, 889 patients without PFC at enrollment in RISK were included. Overall, 41% were female, 70% were &amp;gt;10 yr old. The study included a moderately ill population, including 21% with growth delay, 43% with deep ulcers, and 70% with weighted pediatric Crohn’s disease activity index (wPCDAI) &amp;gt;30. After propensity score matching, 621 remained, including 207 in each treatment group. Propensity score matching was well balanced except more anti-TNF users (76%) had growth delay (26%) than IM (16%) or neither (65%; p=0.002). Regression revealed anti-TNF therapy was associated with 79% reduced odds, and perianal lesions 3-fold increased odds of PFC development. No other characteristic or treatment were significant (Table). Predicted probability of PFC development by each treatment group is depicted in the Figure. CONCLUSIONS In a prospective inception cohort of children with CD who had not yet developed PFCs, only early anti-TNF therapy use was associated with reduced risk of PFC development. These findings corroborate other studies, and indicate early treatment prevents or delays PFC development. Table. Adjusted odds ratio estimates of perianal fistula complications (after propensity matching). Figure. Predicted probability of developing perianal fistulizing complication by treatment group.

P630 Identification of specific cell subsets related to treatment response after anti-tumor necrosis factor use in Korean ulcerative colitis patients using single cell RNA sequencing: a preliminary study

Abstract Background The breakdown of the epithelial barrier and mucosal homeostasis plays an important role in the development of ulcerative colitis (UC). Recently, single-cell RNA sequencing (scRNA-seq) has been performed to better understand the gene expression patterns and the characteristics of cells in intestine of UC patients. However, there is a lack of studies focus on Asian UC patients. The aim of this preliminary study was to identify the relevant cellular subsets related to treatment response after anti-tumor necrosis factor (anti-TNF) use in Korean UC patients using scRNA-seq. Methods This prospective study was conducted two University hospitals in Korea. We performed scRNA-seq on sigmoid colon tissue samples collected from one healthy control and nine biologic naïve UC patients scheduled to use anti-TNF due to lack of response to conventional therapy. All mucosal biopsies from active moderate to severe UC were collected at baseline (n=9) and at 52 weeks follow-up after anti-TNF use (n=2), at which time treatment response was assessed. Treatment responder was defined as those with sustained clinical remission (a partial Mayo score of ≤2 with no subscore &amp;gt;1 and a rectal bleeding subscore of 0) at 52 weeks. Results After processing the scRNA-seq data, 13 clusters were discovered and cell clusters were annotated using colon marker gene. Among nine patients, two patients who underwent response evaluation at 52 weeks after anti-TNF use were treatment responder. The normalized proportion of cluster 1 (stem cell-like cluster) in 52 weeks follow-up tissue samples after anti-TNF use was shown to be decreased significantly (p-value=0.03) from that found in the disease tissue samples. A decrease in the proportion of cell cluster 1 from disease tissue samples’ initial average percentage (30.6%) down to an average of 4.8% in the follow-up tissue samples is quite substantial (p-value=0.03). This decrease signifies a notable change in the composition of this specific cell cluster post-anti-TNF treatment. Moreover, reaching a level close to that of the healthy tissue sample (2.7%) suggests a potential restoration of this cell cluster's proportion towards a healthier state (Figure 1). Conclusion In Korean UC patients, this information should be crucial in understanding the impact of anti-TNF treatment on the cellular composition or behavior of this stem cell-like cluster, suggesting a potential effect of anti-TNF treatment on this particular cell population.

P618 Comparison of vedolizumab and ustekinumab treatment persistence in anti-TNF experienced Crohn's Disease patients

Abstract Background After the approval of vedolizumab and ustekinumab for the treatment of IBD, discussions continue regarding the prioritization of which drug will be used as the first-line treatment. Despite numerous studies in various indications on this matter, there is still no definitive information. It is known that the success of treatments decreases after the use of Anti-TNF in the first step. In this study, we aimed to compare the drug persistence rates of vedolizumab and ustekinumab used as second-line treatments in Crohn's patients with prior experience with Anti-TNF. Methods A total of 171 Anti-TNF experienced Crohn's disease patients were included in this study. Age, gender and other demographical info were recorded from patients electronic medial charts. Drug persistence rates were calculated and compared by using Kaplan-Meier Analysis. Results Seventy eight patients who received vedolizumab and 93 patients who received ustekinumab were analyzed. In vedolizumab group, 60% of the patients were male where as in ustekinumab group, 57% of the patients were male. Mean age was 39.4 years in vedolizumab group and 41.2 years in ustekinumab group. All patients were anti-TNF experienced. In addition, 70% of the patients in ustekinumab group was vedolizumab experienced. Concomitant azathioprine use was 56% in vedolizumab group where as 34% in ustekinumab group. Drug persistence was significantly higher in ustekinumab group when compared to vedolizumab group (Figure 1). Interestingly, concomitant azathioprine use did not change drug persistence in ustekinumab group however it increased drug persistence in vedolizumab group. Conclusion In anti-TNF experienced Crohn's disease patients, ustekinumab treatment persists more longer than vedolizumab treatment. Ustekinumab persistence was independent from concomitant azathiprine use where as concomitant azathioprine use increases vedolizumab persistence.

P677 The Oxford Anti-TNF Study of Immunogenicity and Sustained Response (OASIS-IBD): Analysis of 40,000 Patient Years of Anti-TNF Use

Abstract Background Anti-TNF therapy is established as a mainstay in IBD management. Recent data raise controversies regarding efficacy of these agents, sustainability of response, and identification of factors that may influence outcomes, including dose escalation and need for long-term concurrent immunosuppression (Lancet Gastro.Hep.2019;4:341). Methods We report a retrospective cohort study of 699 IBD patients on anti-TNF at our centre between 2005-2022. Clinical data were obtained from patient records and pharmacy database (TABLE 1). Primary outcomes were overall loss of response (LOR) at any timepoint; and secondary LOR (after an initial clinical response to therapy). Cox regression analysis was performed to identify variables independently affecting outcome. Kaplan-Meyer survival curves were constructed to demonstrate overall response rates (persistence on drug) and secondary LOR (Figure 1a-d). Dose adjustments were made proactively in a Virtual Clinic. Results 204 patients had a diagnosis of ulcerative colitis (UC), 481 Crohn’s Disease (CD) and 14 IBD-unclassified. 126 patients received both infliximab (IFX) and adalimumab (ADA). Median duration on IFX was 42 months (range 0-204); median duration on ADA was 48.5 months (range 0-180). 48% of patients on IFX underwent dose escalation, as did 40% on ADA. Overall, 58 patients (7.6%) remained on treatment at 120 months. Overall survival rates for IFX at 12 months were 83% (82%CD vs. 82%UC); and at 36 months were 71% (69%CD vs. 74%UC). Overall survival rates for ADA at 12 months were 84% (89%CD vs. 59%UC); and at 36 months were 72% (78% CD vs. 42% UC) (Figure 1a-b). Secondary LOR rates for IFX at 12 months were 6% (5%CD vs. 9%UC); and at 36 months were 16% (15%CD vs.19%UC). Secondary LOR rates for ADA at 12 months were 7% (5%CD vs. 19%UC); and at 36 months were 16% (12% CD vs. 42% UC) (Figure 1c-d). There was no difference in survival analysis for IFX between CD and UC. On Cox regression analysis, for IFX, immunomodulation was associated with reduction in overall LOR (HR=0.48, p=1.07e-05) but not secondary LOR (HR=0.78, p=0.31) (Figure 1e-f). For ADA, outcomes were better for CD vs. UC for both overall LOR (HR=0.35, p=3.29e-07) and secondary LOR (HR=0.35, p=9.99e-05). Conclusion We demonstrate encouraging response rates in the first three years of therapy, with a small proportion remaining on therapy beyond 120 months. Survival rates on IFX were similar for UC and CD, but for ADA were significantly lower in UC. Secondary LOR was not affected by immunomodulation. Further analysis of relation to drug levels, dose escalation and genotyping is underway. This work was supported by The Leona M &amp; Harry B Helmsley Charitable Trust.

OP07 Consistent IBD treatment approaches across South Asian and White ethnicities despite phenotypic variations: a study of 33,157 patients using the IBD BioResource

Abstract Background The current evidence suggests ethnic distinctions in IBD phenotype, and differences in the provision of treatment have been reported. This multi-centre cohort study utilised the UK IBD BioResource dataset to evaluate phenotypic differences between South Asian (SA) and White (WH) IBD, and to explore if these were associated with differences in treatment. Methods Phenotypic and outcome data were extracted from the IBD BioResource. Chi2 (categorical data) and Mann-Whitney U (continuous data) tests were used. Propensity score matching (PSM) accounted for age at diagnosis, sex, smoking status, disease location and behaviour and perianal disease (CD). Differences in medication use (multivariable logistic regression) and surgical outcomes (Kaplan-Meier and Cox regression analysis) were assessed in propensity-matched (PM) cohorts. Results 33,157 (31,932 WH; 1225 SA) individuals were included (48.1% CD, 45.4% UC, 6.5% IBD-U). UC was the predominant disease subtype in SA (UC, SA 57.3% vs WH 44.9%, p&amp;lt;0.001). SA were younger at diagnosis [CD, SA 24 (IQR 17-36) vs WH 26 (IQR 19-39) years, p&amp;lt;0.001; UC, SA 29 (IQR 22-38) vs WH 35 (25-48) years, p&amp;lt;0.001]. SA CD had less ileal disease (SA 30.3% vs WH 38.4%, padj=0.008), and more perianal involvement (SA 38.5% vs WH 32.3%, p=0.009) than WH. SA CD had less stricturing disease (SA 16.9% vs WH 25.6%, padj&amp;lt;0.001). SA UC were more likely to have extensive disease (SA 41.7% vs WH 34.1%, padj&amp;lt;0.001). Initial analyses in non-PSM cohorts showed that fewer SA CD underwent surgery [SA (n=157,37.4%) vs WH (n=7532,50.4%), p&amp;lt;0.001], and that similar proportions of SA (n=33,5.1%) and WH (n=747,5.5%; p=0.15) UC underwent a colectomy. PSM was used to match 355 SA to 355 WH in CD, and 525 SA to 525 WH in UC. Variables were well-balanced. There were no differences in 5-ASA, corticosteroid, thiopurine, anti-TNF or Vedolizumab use (Table 1). In CD, 126 (36.5%) SA and 152 (44.7%) had surgery. Survival analysis in CD showed no difference in the time to surgery (Fig 1A, log-rank 0.28). SA ethnicity was not associated with increased risk of surgery in CD (HR 0.82, 95% CI 0.63-1.07, p=0.14). In UC, 25 (4.8%) and 37 (7.1%) WH had a colectomy. There was no significant difference in the time to colectomy (Fig 1B, log-rank 0.12) nor was SA ethnicity associated with an increased risk of having a colectomy (HR 0.65, 95% CI 0.39-1.11, p=0.12). Conclusion In the largest analysis of SA IBD to date, we have demonstrated phenotypic differences associated with ethnicity. Accounting for these variations, we have shown comparable provision of medical and surgical treatment in SA and WH. These findings indicate consistent care of IBD patients from different ethnic backgrounds in the UK.

Safety of Vedolizumab and Ustekinumab Compared With Anti-TNF in Pregnant Women With Inflammatory Bowel Disease

Background and aimsLimited data are available on the consequences of prenatal exposure to vedolizumab and ustekinumab. We aimed to compare the safety of vedolizumab and ustekinumab with that of anti-TNF, in pregnant women with inflammatory bowel diseases (IBD). MethodsUsing nationwide, comprehensive data of the EPI-MERES registry, we identified pregnancies in women with IBD in France, exposed to anti-TNF, vedolizumab, and ustekinumab between 2014 and 2021. We compared pregnancy outcomes and complications in the offspring according to treatment exposure during pregnancy. We applied a propensity score matching for maternal, IBD, and pregnancy characteristics. Results398 pregnancies exposed to vedolizumab were compared to 1,592 pregnancies exposed to anti-TNF; 464 pregnancies exposed to ustekinumab were compared to 1,856 pregnancies exposed to anti-TNF. Overall, compared to anti-TNF, neither vedolizumab nor ustekinumab were associated with increased risks of abortion, caesarean section, stillbirth, preterm birth, serious infections, malignancies, or congenital abnormality in children. Women exposed to ustekinumab had an increased risk of small for gestational age births. ConclusionsOverall, the safety of vedolizumab and ustekinumab compared to anti-TNF use during pregnancy is reassuring. Further studies are needed to confirm these findings.

Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease?

ObjectiveIn this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment. MethodsThe study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study. ResultsOf the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04–67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months. ConclusionOur study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings.

Efficacy and Safety of Anti-Tumor Necrosis Factor Alpha in Very Early Onset Inflammatory Bowel Disease.

Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset in patients younger than 6 years. Challenges in treatment of VEOIBD include lack of approved therapies and increased incidence of monogenic immunodeficiencies. We report on patterns of anti-TNF use, efficacy, and safety in a large cohort of patients with VEOIBD. Very early onset inflammatory bowel disease patients receiving care at a single center were prospectively enrolled in a data registry and biorepository starting in 2012. Whole exome sequencing was available to all patients. Clinical data including IBD medication use and response were extracted from the medical record. We examined antitumor necrosis factor (anti-TNF) cumulative exposure and time to failure and evaluated the effect of covariates on anti-TNF failure using Cox proportional hazard regression. In this cohort of 216 VEOIBD patients with median 5.8-year follow-up, 116 (53.7%) were TNF-exposed. Sixty-two TNF-exposed patients (53.4%) received their first dose at younger than 6 years. Cumulative exposure to anti-TNF was 23.6% at 1 year, 38.4% at 3 years, and 43.4% at 5 years after diagnosis. Cumulative exposure was greater in patients with Crohn's disease (P = .0004) and in those diagnosed in 2012 or later (P < .0001). Tumor necrosis factor failure occurred in 50.9% of those exposed. Features predictive of anti-TNF failure included ulcerative colitis/IBD-unclassified (hazard ratio, 1.94; P = .03), stricturing (hazard ratio, 2.20; P = .04), and younger age at diagnosis (hazard ratio, 1.25; P = .01). Adverse events occurred in 22.6% of infliximab-exposed and 14.3% of adalimumab-exposed. Efficacy and safety of anti-TNFs in VEOIBD is comparable to what has previously been reported in older patients.

Comparison of Disease Phenotype and Course among Elderly- and Early-Onset Inflammatory Bowel Diseases in the Middle East.

It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients. This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes. From 10048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients (P<0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, P=0.001), immunomodulators (44.9% vs 25.2%, P<0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, P=0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6‒0.9, P=0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, P<0.001), immunomodulators (58.7% vs 41.8%, P=0.005) and anti-TNF (49.6% vs 35.4%, P=0.006). Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use.

Rates and Predictors of Long-term Clinical Outcomes in Patients With Perianal Crohn's Disease on Biologic Therapy.

Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies. We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes. We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43). Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.

A Summary of the Rare Reports of Osteonecrosis of the Jaw Associated With Tumor Necrosis-α Inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System Database

Recent case reports highlight an association between osteonecrosis of the jaw (ONJ) and antitumor necrosis factor (anti-TNF) medications. Our study reviewed and described reports of anti-TNF associated ONJ reported to the United States of America's Food and Drug Administration Adverse Event Reporting System to explore this potential adverse drug reaction further. Using the Food and Drug Administration Adverse Event Reporting System database, we identified reported cases of ONJ between 2010 and 2021. Cases were included in our study if they reported any prior or concomitant anti-TNF medication use. Additionally, only adults (age 18+) and reports from health-care professionals were included. Cases lacking subject age or gender were excluded. After duplicates were removed, a dataset was created and demographics were described including age, gender, and indication for use. Naranjo scoring was conducted to assess adverse drug reaction probability. Subject demographics were then separately described for cases without reported denosumab or bisphosphonate therapy history and compared to those with reported history or concomitant denosumab or bisphosphonate therapy. Over twenty thousand cases of ONJ were reported. Forty-four potential cases (0.22%) of anti-TNF medication-associated ONJ were identified and reviewed. Of these, female gender comprised 77.3% (35 cases) and there was an average age of 61.3years±13.7years. Twenty cases (45.5%) had no prior/concomitant bisphosphonate or denosumab therapy. Of these, 55% (11 cases) were female and the average age was 54.5±17.3years. Rheumatoid arthritis was the most frequent indication for use (5 cases, 25%) followed by inflammatory bowel disease (IBD) and psoriatic arthritis (4 cases each, 20%) in this cohort. Twenty potential cases of anti-TNF-associated ONJ without prior or concomitant medications known to be associated with ONJ were identified and described. Interestingly, male gender was more frequent and subjects were younger in these cases compared to those with prior/concomitant bisphosphonates or denosumab therapy. Naranjo scoring indicated a probable interaction for three cases. Further studies are needed to clarify the association of ONJ and anti-TNF therapy, including investigating potential mechanisms and reporting future cases with sufficient detail to assess possible confounding factors.