Ozanimod in Patients With Moderate to Severe Ulcerative Colitis Naive to Advanced Therapies.

BACKGROUND AND AIMS: The pivotal phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis. This analysis assessed ozanimod during TN and the ongoing open-label extension (OLE) in patients with active disease who were naive to advanced therapies (ATs). METHODS: TN was a randomized, double-blind, placebo-controlled trial consisting of a 10-week induction period and 42-week maintenance period. Eligible patients could enter the OLE. Symptomatic efficacy was evaluated from induction through the OLE. Clinical, endoscopic, and mucosal outcomes were evaluated at the end of induction (Week [W] 10) and maintenance (W52), and at predefined OLE timepoints (OLE W46 and W94). Safety during TN was reported. RESULTS: This analysis included 616 AT-naive patients. Numerically greater proportions of patients receiving ozanimod than placebo achieved symptomatic response (39% vs 29%, 95% CI [-0.1, 18.8]) by W2, with significant differences (56% vs 39%, 95% CI [6.3, 26.3]) achieved by W4. Patients receiving ozanimod showed significant improvements across efficacy outcomes versus placebo at W10 and W52 (P<0.05, all endpoints). In patients on continuous ozanimod who entered the OLE in clinical response at W52, 91% maintained clinical response through OLE W94, and 74% achieved endoscopic improvement and 57% achieved mucosal healing at OLE W94. In ozanimod-treated patients without clinical response by W10 who received extended induction in the OLE, 62% achieved symptomatic response by OLE W10. Safety outcomes in AT-naive patients were consistent with the total TN population. CONCLUSION: Ozanimod is an effective, durable, and well-tolerated oral therapy for AT-naive ulcerative colitis patients.

Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

BACKGROUNDS AND AIMS: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis. METHODS: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates. RESULTS: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently. CONCLUSIONS: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry.

INTRODUCTION: We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy. METHODS: Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics. Patients reported the Simple Clinical Colitis Activity Index (SCCAI), Patient-Reported Outcome Measurement Information System measures for anxiety, depression, social satisfaction, and adverse events between weeks 8 and 52 using a web-based system. Paired t test and P for trend were used to compare changes in PRO measures over time. Bivariate analyses and logistic regression models were used to determine factors associated with response (SCCAI <5) or remission (SCCAI <2) at week 52. RESULTS: Of 103 patients, 82.5% entered the maintenance phase and 43.7% remained on tofacitinib at week 52. Tofacitinib de-escalation to 5 mg BID occurred in 15% of patients. At week 52, 42.7% and 31.1% of all patients reported an SCCAI <5 and SCCAI ≤2, respectively. Normalization of bowel frequency, rectal bleeding, and urgency occurred in 79%, 61%, and 48% of patients remaining on maintenance therapy. Social satisfaction improved significantly ( P < 0.001), while anxiety and depression scores only numerically improved. No consistent predictors for tofacitinib long-term treatment efficacy were identified, and safety findings were consistent with the known safety profile of tofacitinib. DISCUSSION: Tofacitinib is an effective maintenance therapy in patients with refractory UC. Dose reductions infrequently occurred during maintenance. Unmet needs in UC maintenance include improvement of urgency and psychosocial factors (NCT03772145).

Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial.

BACKGROUND: Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study. METHODS: We did a phase 2, randomised, multicentre, double-blind trial. Adult patients with moderately to severely active Crohn's disease were randomly allocated with a computer-generated randomisation schedule to receive one of five treatment groups, with regimens consisting of an intravenous induction phase transitioning to a subcutaneous maintenance phase starting at week 12 in a treat-through design: (1) guselkumab 200→100 mg group (200 mg intravenous at weeks 0, 4, and 8, then 100 mg subcutaneous every 8 weeks; (2) guselkumab 600→200 mg group (600 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (3) guselkumab 1200→200 mg group (1200 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (4) ustekinumab group (approximately 6 mg/kg intravenous at week 0, then 90 mg subcutaneous every 8 weeks); or (5) placebo group (placebo induction followed by either placebo maintenance [for those with CDAI clinical response at week 12] or crossover to ustekinumab [for those without CDAI clinical response at week 12]). Endpoints assessed at week 48 included CDAI remission (CDAI score <150), endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD score ≤2), and endoscopic remission (SES-CD score ≤2) in the primary efficacy analysis population of all randomised patients who received at least one dose of study drug, excluding those discontinued during a temporary study pause. Safety analyses included all randomised patients who received at least one study drug dose. This trial is registered at Clinical Trials.gov (NCT03466411) and is active but not recruiting. FINDINGS: Among 700 patients screened, 309 (112 biologic-naive; 197 biologic-experienced) were included in the primary efficacy analysis population: 61 in the guselkumab 200→100 mg group, 63 in the guselkumab 600→200 mg group, 61 in the guselkumab 1200→200 mg group, 63 in the ustekinumab group, and 61 in the placebo group. 126 (41%) women and 183 (59%) men were included, with median age 36·0 years (IQR 28·0-49·0). At week 48, the numbers of patients with CDAI clinical remission were 39 (64%) in the guselkumab 200→100 mg group, 46 (73%) in the guselkumab 600→200 mg group, 35 (57%) in the guselkumab 1200→200 mg group, and 37 (59%) in the ustekinumab group. The corresponding numbers of patients with endoscopic response were 27 (44%), 29 (46%), 27 (44%), and 19 (30%), respectively, and endoscopic remission was seen in 11 (18%), 11 (17%), 20 (33%), and four (6%) patients, respectively. In the placebo group, 15 patients were in CDAI clinical response at week 12 and continued placebo; of these, nine (60%) were in clinical remission at week 48. 44 patients in the placebo group were not in CDAI clinical response at week 12 and crossed over to ustekinumab; of these, 26 (59%) were in clinical remission at week 48. Up to week 48, adverse events frequencies in the safety population (n=360) were 46 (66%) of 70 patients (464·9 events per 100 patient-years of follow-up) in the placebo group, 163 (74%) of 220 patients (353·1 per 100 patient-years) in the three guselkumab groups combined, and 60 (85%) of 71 patients (350·7 per 100 patient-years) in the ustekinumab group. Among patients treated with guselkumab or ustekinumab, the most frequently reported infections up to week 48 were nasopharyngitis (25 [11%] of 220 guselkumab recipients, 12 [11%] of 114 ustekinumab recipients) and upper respiratory infections (13 [6%] guselkumab recipients, eight [7%] ustekinumab recipients). After week 12, one patient who responded to placebo induction and two guselkumab-treated patients had serious infections. No active tuberculosis, opportunistic infections, or deaths occurred. INTERPRETATION: Patients receiving guselkumab intravenous induction and subcutaneous maintenance treatment achieved high rates of clinical and endoscopic efficacy up to week 48. No new safety concerns were identified. FUNDING: Janssen Research & Development.

Unmet Needs in Real-World Advanced Therapy-Naïve and -Experienced Patients with Moderately to Severely Active Ulcerative Colitis in the United States.

INTRODUCTION: Despite availability of advanced therapies (ATs) for ulcerative colitis (UC), many patients fail to respond to treatment. This study examined real-world clinical and humanistic outcomes associated with current treatments in patients with UC. METHODS: This cross-sectional study used US data from the Adelphi Real World Disease Specific Programme for inflammatory bowel disease from before (2017-2018) and during the COVID-19 pandemic (2020-2021). Physicians (gastroenterologists) seeing > 5 patients/month reported patients' disease characteristics, current symptoms and treatments, and reasons for treatment choices for their next seven consecutive patients aged ≥ 18 years with moderately to severely active UC before current treatment. Patients were asked to complete the EQ-5D-5L health-related quality of life (HRQoL) measure. ATs included tumor necrosis factor inhibitors (TNFis), integrin receptor antagonists, interleukin-12/23 antagonists, and Janus kinase inhibitors. Patients were classified as AT-naïve or AT-experienced based on current treatment received for ≥ 8 weeks and further classified as responders or non-responders based on symptoms, disease flare status, and remission. Descriptive analyses are presented. RESULTS: The 2017-2018 cohort included 92 physicians and 539 patients (208 [38.6%] AT-experienced). The 2020-2021 cohort included 73 physicians and 448 patients (349 [77.9%] AT-experienced). TNFis were the most common ATs. In 2017-2018, 195 (58.9%) AT-naïve and 113 (54.3%) AT-experienced patients were non-responders; in 2020-2021 this was 57 (57.6%) and 182 (52.1%). Efficacy and induction of remission were physicians' most common reasons for AT choice. Dislike of injections/infusions was the most common reason for eligible patients not receiving biologic therapy. Numerically, non-responders (both AT-naïve and AT-experienced) had more symptoms, overall pain and fatigue, and lower HRQoL scores than responders. CONCLUSIONS: Before (2017-2018) and during the pandemic (2020-2021), over half of patients with UC did not respond to AT. Non-responders carried a high burden of disease. Alternative therapies are urgently needed to treat UC.

Indications and safety of newer IBD treatments in the older patient.

PURPOSE OF REVIEW: Treatment of inflammatory bowel disease (IBD) in the elderly requires special attention to treatment efficacy while considering drug safety, other medical comorbidities, and the patients' risk for treatment related adverse events. In this article, we reviewed the indications and safety of the newer IBD therapies in the older IBD patient beyond anti-TNF agents, thiopurines, and corticosteroids. RECENT FINDINGS: Vedolizumab, ustekinumab, and risankizumab have favorable side effect profiles with regards to infections and malignancy. Ozanimod has a favorable side effect profile with regards to infection and malignancy, however cardiac events and macular edema are potential risks. Tofacitinib and upadacitinib are associated with an increased risk of serious infections, herpes zoster, malignancy, and have potential for an increased risk of cardiac events and thrombosis. From a safety profile perspective, vedolizumab, ustekinumab, and risankizumab should be considered first line treatment options for moderate-to-severe IBD in the elderly. Risk-benefit discussions are indicated for ozanimod, tofacitinib, and upadacitinib.

Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting.

BACKGROUND: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. METHODS: Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI ≤2) by clinical factors. RESULTS: Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. CONCLUSIONS: In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and Persistence With Inflammatory Bowel Disease Therapy (ASSIST Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract. Although adherence to IBD therapies is associated with improved clinical outcomes, overall adherence is poor. Consequently, there is a critical need to develop interventions that monitor adherence in real time and identify reasons for nonadherence to support clinical teams in initiating effective interventions. Recently, electronic- and web-based platforms have been developed to monitor adherence and guide interventions. A novel remote therapy monitoring (RTM) technology, the Tappt digital health system, has been developed to monitor real-time medication adherence patterns through smart label technologies, capture patient-reported outcomes and barriers to care, and process patient data through algorithms that trigger personalized digital and human touch points between clinical visits. Such a digital health solution enables care teams to proactively identify and mitigate nonadherence and worsening clinical outcomes. OBJECTIVE: We propose a 12-month multicenter randomized controlled trial to assess the effectiveness of the Tappt digital health system on adherence, clinical outcomes, and health care use among patients diagnosed with IBD starting a new oral or subcutaneous therapy. METHODS: The digital health system intervention will provide automatic measurement of medication adherence via smart labels for pill bottles or injectors as well as a monitoring platform for providers. The system will prompt patients to complete a two-item assessment of symptoms monthly using the PRO-2 scales for UC and Crohn disease, from which increased symptoms will be alerted to providers. Participants will be randomized 2:1 to the intervention group or the control group, which will receive standard of care. All participants are required to complete questionnaires at baseline as well as at 12, 26, and 52 weeks. Assuming an adherence rate of 0.65 and 0.9 among control and intervention participants, respectively, we will need to enroll 123 participants: 82 (66.7%) in the intervention group and 41 (33.3%) controls. We will compare adherence as measured by the medication possession ratio, defined as the number of days of supply of medication obtained during the observation period out of the total number of days in the observation period, in participants using the RTM versus those receiving standard of care. We will also compare clinical outcomes and health care use in participants using the RTM versus those receiving standard of care. RESULTS: We anticipate starting recruitment in December 2022. CONCLUSIONS: Effective medication adherence monitoring and intervention programs need to be cost-efficient, pose little or no burden to the patient, record reliable data in real time, and provide actionable insights to the health care team. We anticipate the Tappt digital health system to improve the medication possession ratio, clinical outcomes, and health care use compared with standard of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05316584; https://clinicaltrials.gov/ct2/show/NCT05316584. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40382.

Ozanimod as a novel oral small molecule therapy for the treatment of Crohn's disease: The YELLOWSTONE clinical trial program.

BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate receptor modulator currently approved for the treatment of moderately to severely active ulcerative colitis and relapsing multiple sclerosis, showed clinical, endoscopic, and histological benefit in the phase 2 STEPSTONE trial for Crohn's disease (CD). We aim to describe the trial design of the YELLOWSTONE phase 3 program evaluating the safety and efficacy of ozanimod in patients with moderately to severely active CD. METHODS: The YELLOWSTONE program consists of phase 3, randomized, double-blind, placebo-controlled induction (NCT03440372 and NCT03440385) and maintenance (NCT03464097) trials and an open-label extension (OLE) study (NCT03467958). Patients with inadequate response or intolerance to ≥1 CD treatment are randomized to receive daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo for 12 weeks during induction. Those who respond to ozanimod are rerandomized to continue ozanimod or placebo maintenance therapy for 52 weeks. Patients who do not meet criteria for maintenance, experience relapse during maintenance, or complete maintenance or ≥ 1 year of STEPSTONE are eligible for open-label treatment for up to 234 weeks. Efficacy endpoints include clinical, endoscopic, and histologic outcomes. RESULTS: Expected 2023 (induction studies), 2024 (maintenance study), and 2026 (OLE). CONCLUSION: YELLOWSTONE will provide pivotal phase 3 data on the safety and efficacy of ozanimod in patients with moderately to severely active CD using state-of-the-art methods, including centrally read endoscopic and histologic measurements, along with subjective assessments of symptom control based on the Crohn's Disease Activity Index. These studies could enable approval of ozanimod as a new CD therapy. CLINICAL TRIAL REGISTRATION NUMBERS: NCT03440372, NCT03440385, NCT03464097, NCT03467958.

Recommendations on the Appropriate Management of Steroids and Discharge Planning During and After Hospital Admission for Moderate-Severe Ulcerative Colitis: Results of a RAND Appropriateness Panel.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

Pregnant women with immune mediated inflammatory diseases who discontinue biologics have higher rates of disease flare.

BACKGROUND AND AIMS: Biologic agents have revolutionized treatment of immune mediated inflammatory diseases (IMIDs). However, despite the benefits of treatment, there is limited data on its use during pregnancy leading to significant variation in practices. We evaluated maternal, neonatal, and disease-related outcomes in pregnant women with IMIDs, comparing those with biologic exposure during pregnancy to those without exposure. Our hypothesis was that there would be no difference in outcomes between the two groups. METHODS: This is a retrospective cohort study conducted at a single tertiary care center including women with Crohn's disease (CD), ulcerative colitis (UC), ankylosing spondylitis (AS), rheumatoid arthritis (RA), or psoriasis/psoriatic arthritis (PS/PsA) who delivered between 2010 and 2018 at The Ohio State University Wexner Medical Center. Conditions were identified by ICD-9/ICD-10 code and confirmed by chart review. Demographic data, pregnancy outcomes and disease-related data were collected. RESULTS: There were 338 pregnancies including 100 with CD, 74 with UC, 15 with AS, 61 with RA, and 90 with PS/PsA. 23% of IMID patients had biologic exposure (biologic use within 3 months of conception) and 18% continued therapy during pregnancy. Those with biologic exposure had increased risk of post-partum disease flare (OR 3.44; 95% CI 1.29, 9.15) and were less likely to breastfeed (OR 0.44; 95% CI 0.23, 0.87). In subgroup analysis of patients with IBD, those with biologic exposure also had increased risk of post-partum flare (OR 4.55; 95% CI 1.27, 16.35). Maternal and neonatal pregnancy outcomes were similar. CONCLUSION: Among pregnant women with IMIDs, those that continued biologics during pregnancy had increased rates of major infection, disease related hospital admission, glucocorticoid use, and disease flare within 6 months post-partum, without any significant change in maternal or neonatal outcomes.

Guselkumab for the Treatment of Crohn's Disease: Induction Results From the Phase 2 GALAXI-1 Study.

BACKGROUND & AIMS: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis. This study evaluated the efficacy and safety of guselkumab in patients with moderately to severely active Crohn's disease with inadequate response or intolerance to conventional or biologic therapy. METHODS: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. Change from baseline in Crohn's Disease Activity Index score (primary end point), clinical remission, clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, endoscopic response (major secondary end points), and safety in guselkumab-treated patients vs placebo were evaluated through week 12. Ustekinumab was a reference arm. RESULTS: Of 309 patients evaluated, approximately 50% had disease refractory to prior biologic therapy. At week 12, significantly greater reductions in Crohn's Disease Activity Index from baseline (least squares means: 200 mg: -160.4, 600 mg: -138.9, and 1200 mg: -144.9 vs placebo: -36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo (Crohn's Disease Activity Index <150; 57.4%, 55.6%, and 45.9% vs 16.4%; all, P < .05). Greater proportions of patients receiving guselkumab achieved clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, and endoscopic response at week 12 vs placebo. Efficacy of ustekinumab vs placebo was also demonstrated. Safety event rates were generally similar across treatment groups. CONCLUSIONS: At week 12, all 3 dose regimens of guselkumab induced greater clinical and endoscopic improvements vs placebo, with a favorable safety profile. CLINICALTRIALS: gov, Number: NCT03466411.

Impact of Cannabis Use on Inpatient Inflammatory Bowel Disease Outcomes in 2 States Legalizing Recreational Cannabis.

Background: We evaluated the impact of recreational cannabis legalization on use and inpatient outcomes of patients with inflammatory bowel disease (IBD). Methods: Hospitalized adult patients in Colorado and Washington before (2011) and after (2015) recreational cannabis legalization were compared by chi-square tests for categorical variables and t-tests for continuous variables. Multivariable regression models adjusting for demographic data were fit to assess the association of cannabis use with hospital outcomes. Results: Reported cannabis use increased after legalization (1.2% vs 4.2%, P < .001). On multivariable analysis, in 2011, cannabis users were less likely to need total parenteral nutrition (odds ratio 0.12, P = .038), and in 2015 had less hospital charges ($-8418, P = .024). Conclusions: The impact of cannabis legalization and use on IBD is difficult to analyze but may have implications on inpatient IBD outcomes as described in this retrospective analysis. Large, prospective studies are needed to evaluate other IBD outcomes based on cannabis legalization and use.

Health Maintenance Consensus for Adults With Inflammatory Bowel Disease.

BACKGROUND: With the management of inflammatory bowel disease (IBD) becoming increasingly complex, incorporating preventive care health maintenance measures can be challenging. The aim of developing these updated recommendations is to provide more specific details to facilitate their use into a busy clinical practice setting. METHOD: Fifteen statements were formulated with recommendations regarding the target, timing, and frequency of the health maintenance interventions in patients with IBD. We used a modified Delphi method and a literature review to establish a consensus among the panel of experts. The appropriateness of each health maintenance statement was rated on a scale of 1 to 5 (1-2 as inappropriate, and 4-5 as appropriate) by each panelist. Interventions were considered appropriate, and statements were accepted if ≥80% of the panelists agreed with a score ≥4. RESULTS: The panel approved 15 health maintenance recommendations for adults with IBD based on the current literature and expert opinion. These recommendations include explicit details regarding specific screening tools, timing of screening, and vaccinations for adults with IBD. CONCLUSIONS: Patients with IBD are at an increased risk for infections, malignancies, and other comorbidities. Given the complexity of caring for patients with IBD, this focused list of recommendations can be easily incorporated in to clinical care to help eliminate the gap in preventative care for patients with IBD.

Impact of rapid infliximab infusions on access at a large academic tertiary medical center.

PURPOSE: Infliximab promotes remission in patients with inflammatory bowel disease (IBD) and rheumatologic disease (RD). Rapid infliximab infusions (RI) reduce infusion time from 2 hours to 1 hour and can enhance access to care, as defined by capacity, safety, and patient characteristics. Our hypothesis for the study described here was that use of RI can enhance access for patients. METHODS: Data on all patients receiving infliximab for IBD or RD at our outpatient infusion center from February 2016 to August 2017 were retrospectively analyzed. Demographic and clinical information were collected. RESULTS: Of 348 patients who received infliximab, 205 had IBD and 143 had RD. In terms of capacity, 40% of patients received RI, resulting in a 16.1% decrease in average daily infusion time and a 9.8% increase in average daily available scheduled infusion chair time (P = 0.720). In terms of safety, 4 patients switched back to standard infusions after RI, after 3 specifically had reactions to RI. In terms of patient characteristics, more patients with RD versus IBD received RI (P = 0.020). Among the patients with RD, a lower proportion receiving RI were female (P = 0.043). For the patients with IBD, a higher proportion receiving RI were White (P = 0.048). Among both patients with RD and patients with IBD, a higher proportion receiving RI had private insurance (P = 0.016 and P = 0.018, respectively). CONCLUSION: RI were safe and increased available chair time. Females with RD, patients of non-White race with IBD, and patients with public insurance were less likely to receive RI. Future directions include patient surveys and evaluation of implicit bias against patient factors that may impact access to RI.

The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable.

In the USA, an interchangeability designation provides biosimilar sponsors with a pathway for achieving what is standard for small-molecule generics: pharmacy-level auto-substitution for an innovator. No other major health authority links interchangeability to automatic substitution, as all require the involvement of the prescriber or patient in a medication change. This editorial considers the clinical impact and practicality of auto-substitution. First, interchangeability is linked to non-medical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons. NMS may generate negative sentiment in those unwilling or reluctant to switch, which can adversely impact treatment outcomes (i.e., nocebo effect). Indeed, in real-world studies of tumor necrosis factor inhibitors, discontinuation rates have been shown to be higher in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators. Second, interchangeability may impede pharmacovigilance and traceability, as not all jurisdictions require innovators and biosimilars to have distinct biologic names. Third, an interchangeability designation from the US Food and Drug Administration only permits a biosimilar to be automatically substituted for its innovator, not other biosimilars (if available). Pharmacist education would be needed to avoid off-label, automatic substitution among biosimilars of a single innovator. Last, once granted, an interchangeability designation exists in perpetuity under current US federal law. However, the supply chains of innovators and biosimilars are maintained independently, with no requirement for reconfirmation of biosimilarity or interchangeability. We feel that additional guidance is needed for the auto-substitution of biosimilars and innovators to become a reality.