Biologics In Crohn's Disease Research Articles

Upadacitinib (Rinvoq)


 CADTH recommends that public drug plans reimburse Rinvoq for the treatment of moderately to severely active Crohn disease (CD) if certain conditions are met.
 Rinvoq should only be covered to treat adult patients with moderately to severely active CD who do not respond to, stop responding to, or who cannot tolerate conventional or biologic therapies, provided that Rinvoq is covered for a similar patient population and in a similar way to biologic therapies currently reimbursed by public drug plans for the treatment of adult patients with moderately to severely active CD.
 Rinvoq should only be reimbursed if prescribed by a physician experienced in the diagnosis and management of CD, if it is not used in combination with biologics for CD, and if the cost of Rinvoq is reduced so that it does not cost the drug programs more than the least costly biologic therapy reimbursed for the treatment of moderately to severely active CD. Patients must respond to treatment in the first 12 weeks of starting Rinvoq to continue receiving the drug.

Durability of the First Biologic in Patients with Crohn's Disease: A Nationwide Study from the epi-IIRN.

In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease [CD], stratified by monotherapy and combotherapy. We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population [2005-2020]. Durability was defined as consistent treatment without surgery or added medications [except for combination therapy with thiopurines or methotrexate]. All comparisons were based on stringent propensity-score matching and paired time-to-event analyses. A total of 19 264 patients with CD were included, of whom 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [IQR] 3.6-10.7). Time to biologics decreased gradually from 6.7 years [IQR 2.7-10.4] in 2005 to 0.2 years [0.07-0.23] in 2020. The durability of the first biologic after 1 and 3 years was higher with adalimumab monotherapy [88%/61%] than vedolizumab monotherapy [81%/59%; n = 394 matched patients, p = 0.04] and similar between infliximab monotherapy and vedolizumab monotherapy [65%/43%; n = 182 matched patients, p = 0.1]. Durability was higher in adalimumab monotherapy vs infliximab monotherapy [83%/62% vs 71%/48% at 1/3 years; p <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n = 496 matched pairs, p <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n = 540 matched pairs, p <0.001]. Durability of the first biologic in CD was highest for adalimumab monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised.

Use, Durability, and Risks for Discontinuation of Initial and Subsequent Biologics in a Large Pediatric-Onset IBD Cohort.

Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic. We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation. Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). Biologic treatment was more likely for CD than UC (odds ratio, 3.0; 95% CI: 2.8-3.2; P < 0.0001). First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab). Probability of remaining on the first biologic was significantly higher in CD than UC ( P < 0.0001). First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%). In univariate analysis, factors associated with discontinuation of first and/or second biologics in CD include colonic-only disease, corticosteroid use, upper gastrointestinal tract involvement, and clinical and biochemical markers of severe disease. Biologic durability improved with later induction date. Treatment with biologic medications is common in pediatric IBD. Patients with CD are more likely to receive biologics, receive biologics earlier in disease course, and remain on the first biologic longer than patients with UC. Multiple factors may predict biologic durability in children with IBD.

Two-year real-world outcome data from a single tertiary centre shows reduced ustekinumab persistence in a non-bio-naïve Crohn's disease cohort with penetrating disease, -ostomies and sarcopenia.

Ustekinumab was approved in 2016 for the treatment of moderate-severe Crohn's disease (CD). Clinical trials and real-world studies have suggested ustekinumab to be a safe and effective treatment; however, studies to date infrequently use imaging techniques to predict response to biologics in CD. We assessed the 2-year real-world effectiveness and safety of ustekinumab in a tertiary CD cohort with the use of novel imaging techniques. Retrospective cohort study. Retrospective data were collected between 2016 and 2021. Study end points included ustekinumab persistence, biological and/or clinical response and remission at 12, 18 and 24 months. Statistical analysis included demographic and inferential analyses. In all, 131 CD patients [57.3% female, median age of 26.0 (21.0-37.0)] were included. Patients were non-bio naïve, and the majority received ustekinumab as third- or fourth-line treatment. At 24 months, 61.0% (80/131) persisted with ustekinumab [52.7% (69/131) steroid free]. Clinical response was reported in 55.2% (37/67), clinical remission in 85.7% (57/67), biological response in 46.8% (22/47) and biological remission in 31.9% (15/47) of patients at 24 months. The low outcome numbers were attributable to missing data. Improvements in routine disease markers, including C-reactive protein and Harvey-Bradshaw Index, were also reflected in magnetic resonance imaging-derived disease scores. The presence of penetrating CD, an -ostomy and sarcopenia were all predictors of poorer ustekinumab outcomes (p < 0.05). Ustekinumab is effective in non-bio-naïve CD patients with non-stricturing, non-penetrating disease with an unremarkable safety profile but may be less effective in those with penetrating disease, -ostomies and sarcopenia.

Treatment patterns, persistence with therapy, and outcomes of ustekinumab in Crohn's disease: Real-world data analysis.

Background and AimIn 2017, ustekinumab (UST) was included in Israel's National Basket of Health Services for treatment of biologic‐experienced Crohn's disease (CD) patients with moderately to severely active disease. This study aims to provide real‐world evidence on persistence and clinical outcomes among early users of UST.MethodsThis retrospective cohort study was conducted using data from Maccabi Healthcare Services (MHS; 2.5‐million‐member state‐mandated health provider, Israel). Adult patients with a CD diagnosis code who had ≥1 dispensed UST prescription in 2017–2018 and at least 12 months of prior continuous health plan enrollment were included. Outcomes, including treatment discontinuation, dose‐escalation (based on shortened intervals between purchases), CD‐related surgery, CD‐related hospitalization, corticosteroid (CS) discontinuation, and use of opioids were evaluated from the date of first dispensed UST through the end of 2019 using Kaplan–Meier analysis.ResultsA total of 162 eligible patients (81 [49.4%] female; median age 34.4 years [IQR 23.2–46.3]; median years since CD diagnosis 8.6 [IQR 4·8–16.0]) were enrolled in the study. Discontinuation rate after 365 and 540 days of follow‐up was 27.8% and 35.6%. Dose escalation was estimated at 15.4% and 28.6%, respectively. The first‐year cumulative rate of CD‐related surgery and CD‐related hospitalization were estimated at 4.7% and 9.8%, respectively.ConclusionIn this real‐world CD cohort of UST users, results suggest persistence is relatively high as compared to other biologics for CD. Comparative effectiveness of different biologic treatments for CD in this population should be further explored.

Safety and Efficacy of Tofacitinib in Combination With Biologic Therapy for Refractory Crohn's Disease.

The majority of patients with Crohn's disease (CD) will not achieve endoscopic remission on current therapy. Addition of tofacitinib to biologics may improve remission rates. We retrospectively assessed safety and clinical and endoscopic effectiveness of off-label tofacitinib and biologics for CD. We identified 19 patients treated with tofacitinib and a biologic for refractory CD between 2017 and 2019. Tofacitinib was added for luminal disease on colonoscopy (n = 13), luminal disease on capsule (n = 3), and pyoderma gangrenosum (n = 3). The mean age was 41.2 years (28-62), mean disease was duration 16.9 years (6-36), and prior exposure to biologics was a median of 4 (1-6). Mean treatment duration was 9.6 months (SD, 3.3). Adverse events (AEs) were reported in 36.8% of patients, most commonly minor infection or CD flare, and no patients had a serious AE; 80.0% (n = 8) achieved clinical response, and 60.0% (n = 6) achieved clinical remission based on Harvey-Bradshaw Index. Endoscopic improvement occurred in 54.5% (n = 6), endoscopic remission in 18.2% (n = 2), and endoscopic healing in 18.2% (n = 2) of patients. Mean Simple Endoscopic Score in CD significantly improved from 13.6 ± 5.2 to 6.5 ± 4.0 after treatment (P < .01). In patients treated with tofacitinib in combination with a biologic, no new safety signals were observed. Combination tofacitinib and a biologic was effective in achieving clinical and endoscopic improvement in some patients with severe, refractory CD, although a larger sample size is needed to further assess the efficacy and long-term safety of this treatment strategy.

Positioning biologics in the management of moderate to severe Crohn's disease.

Since there is a lack of head-to-head randomized controlled trials, little direction is provided from guidelines on the positioning of biologics for the treatment of Crohn's disease (CD). This review utilizes comparative effectiveness and safety results from real-world data and network meta-analyses to inform clinical practice for positioning of biological therapies in the treatment of moderate-to-severe CD. We summarize the results of studies pertaining to the identification of predictors for response to biologics in CD. Recently published studies about the management of moderate-to-severe CD are discussed and a positioning algorithm is proposed for the therapeutic approach of these patients. Different classes of biologics are comparable with regards to safety and almost similar in effectiveness in the management of CD. There are certain clinical scenarios in which one biologic is more effective than another. For instance, patients with a more aggressive disease phenotype such as fistulizing disease would benefit from infliximab over other biologics, whereas in older patients at a higher risk for infectious complications, it may be more appropriate to use ustekinumab or vedolizumab over the anti-tumor necrosis factor (TNF) agents. More data pertaining to identifying predictors of response to the different available therapies and head-to-head comparison trials are needed to personalize our therapeutic approach of CD patients.