Search

Upadacitinib was superior to placebo across clinical, endoscopic, and histologic endpoints; was effective in achieving corticosteroid-sparing treatment; and was well tolerated in the U-ACHIEVE maintenance study. In the U-ACTIVATE LTE trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled clinical program, corticosteroid-free and symptomatic remission was achieved with upadacitinib maintenance treatment and was maintained in more than 80% of patients through 48 weeks. Patients from the LTE study were further assessed up to 96 weeks. Most of these patients achieved and maintained corticosteroid-free CR, suggesting that upadacitinib continues to have a persistent benefit, is an excellent long-term treatment option for moderately to severely active UC, and can spare patients from corticosteroid use. [ABSTRACT FROM AUTHOR]

Post hoc analysis of data from this prospective study found no significant difference in efficacy of therapy in patients who had a clinical response or patients on monotherapy or on immunosuppression at week 52 or 104. Although the rate of antidrug antibodies was lower with combination therapy, there was no difference in efficacy, biomarker profiles, or safety outcomes. If this study was conducted in a fashion similar to the SONIC trial, in which half of patients were prospectively randomized to monotherapy and half were given combination therapy, differences may have been observed, such as better outcomes in those on an immunomodulator and CT-P13 SC. [ABSTRACT FROM AUTHOR]

A benefit with risankizumab compared with placebo was observed in patients with an inadequate response to prior nonadvanced therapy (29.7% vs 8.4%) and in patients with an inadequate response to prior advanced therapy (11.4% vs 4.3%). In this study, there were several important findings: (1) the proportion of patients who had prior failure to advanced therapy was numerically higher for patients who did not achieve CR or EI at maintenance week 0 than for those who achieved it; (2) the rates of each clinical, endoscopic, and histologic outcome were generally numerically higher with risankizumab vs placebo regardless of CR or EI status at maintenance week 52; and (3) among patients with clinical response to the induction treatment who did not achieve CR or EI, risankizumab 360 mg SC demonstrated numerically higher rates of improvement in all presented outcomes over risankizumab 180 mg SC at maintenance week 52. This study highlights that exposure to risankizumab was associated with improved outcome regardless of week 12 (early) outcomes. [ABSTRACT FROM AUTHOR]

This study demonstrated that mirikizumab maintained endoscopic and histologic outcomes through an additional 2 years of continuous treatment for a total of 3 years. In addition, individuals who achieved long-term durable and sustained endoscopic and histologic outcomes with mirikizumab had in aggregate achieved an overall better health-related QOL. Remarkably, nearly three-quarters (70%) of patients who achieved CR at week 52 were able to achieve histologic and endoscopic remission without neutrophils on histology at week 152, and nearly half (47%) of all clinical remitters at week 52 were able to achieve endoscopic normalization at week 152. [ABSTRACT FROM AUTHOR]

It is recognized that individuals with prior exposure to anti-tumor necrosis factor (TNF) drugs often have a lower chance of success with subsequent anti-TNF therapies (ie, the effectiveness may be reduced and patients may be less likely to achieve remission or may require switching to a different medication class altogether). Similar findings have been seen with S1P receptor modulators. This study evaluated pooled induction data from 4 randomized controlled trials (1562 patients) and related that S1P receptor modulators may be more effective in inducing CR compared with placebo in patients with moderately to severely active UC and prior biologic exposure. The same finding has been seen in UC patients with prior biologic use who initiate JAK inhibitor therapy, whereas the GEMINI trials have shown that vedolizumab is more effective in patients who have not previously received anti-TNF medications compared with patients with prior failure of anti-TNF therapy. [ABSTRACT FROM AUTHOR]

In the True North Study, which assessed ozanimod vs placebo, it is comforting to see that no new safety concerns were identified. A significant number of patients (43%) persisted on medication for up to 5 years. The rate of treatment discontinuation owing to AEs was low. With 2681 PY of follow-up, the study has not yet achieved adequate power to assess for the presence of uncommon events such as lymphoma. Continued follow-up will be necessary. [ABSTRACT FROM AUTHOR]

Clinically meaningful improvements in endoscopic and histologic outcomes compared with placebo (guselkumab withdrawal) were notably present in both the biologic/JAK inhibitor--naive patient subpopulation and also in the patients who had an inadequate response or intolerance to biologics and/or JAK inhibitors. As expected, patients who received placebo after responding to initial therapy had progressive worsening of histologic and combined histologic and endoscopic outcomes. The findings of this study have important clinical implications for patient care. [ABSTRACT FROM AUTHOR]

In the QUASAR phase 3 induction trial, guselkumab was demonstrated to be effective for achieving CR in patients with moderately to severely active UC. In the QUASAR randomized withdrawal maintenance study, 50.0% (P<.001) of patients with moderately to severely active UC receiving SC guselkumab 200 mg every 4 weeks and 45.2% (P<.001) of patients receiving SC guselkumab 100 mg every 8 weeks achieved the primary endpoint of CR at week 44 compared with placebo (18.9%). Among patients with moderately to severely active UC who were receiving concomitant oral corticosteroids at maintenance baseline, the majority of guselkumab-treated patients eliminated corticosteroids within 8 weeks. These impressive and clinically relevant findings highlight the fact that patients who were receiving maintenance treatment with guselkumab who achieved CR at week 44 did so without concomitant use of oral corticosteroids. [ABSTRACT FROM AUTHOR]

Of the patients who did not initially respond to 3 induction doses, 60.6% (123 of 203) achieved clinical response to 3 further doses and entered the maintenance study phase. This more refractory population of UC patients (who did not respond initially by week 12 but did respond after 3 further doses of guselkumab 200 mg SC at weeks 12, 16, and 20) had higher UC disease burden and were able to maintain or improve endoscopic, histologic, symptomatic, and QOL outcomes. Safety results were consistent with the overall population and safety profile of guselkumab in its approved indications. Overall, the results support continuing guselkumab treatment in this more refractory patient population. [ABSTRACT FROM AUTHOR]

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Aim: To report efficacy and infection rates in patients receiving tofacitinib induction treatment, by baseline corticosteroid status. Methods: We evaluated efficacy and safety data from OCTAVE Induction 1&2 in patients with moderately-to-severely active ulcerative colitis who received tofacitinib 10 mg twice daily or placebo for 8 weeks, based on induction baseline oral corticosteroid use (Corticosteroid-Yes/No) and dose (< 20/ ≥ 20 mg/day). Infections of interest included serious infections, herpes zoster (HZ), and adjudicated opportunistic infections (OIs). Results: At OCTAVE Induction 1&2 baseline, 478/1092 (43.8%) patients were receiving corticosteroids. Tofacitinib demonstrated significant induction efficacy versus placebo for both Corticosteroid-Yes and Corticosteroid-No. With adjustment for prior tumor necrosis factor inhibitor and immunosuppressant failure, there were no statistically significant differences in remission and clinical response rates for Corticosteroid-Yes versus Corticosteroid-No. Among tofacitinib-treated patients, HZ and OIs occurred more frequently in Corticosteroid-Yes versus Corticosteroid-No, regardless of dose (< 20 mg vs. ≥ 20 mg). Infection incidence rates (regardless of severity/seriousness) during tofacitinib induction were generally similar regardless of baseline corticosteroid use. The proportion of tofacitinib-treated patients with HZ was 0.2% for Corticosteroid-No versus 1.1% for Corticosteroid-Yes < 20 mg and 1.0% for Corticosteroid-Yes ≥ 20 mg. Two out of three patients had HZ OIs. Conclusions: Tofacitinib induction efficacy (clinical response and remission) was similar in baseline corticosteroid subgroups. Infections of interest were rare; HZ and OIs occurred more frequently among those receiving tofacitinib and corticosteroids versus those receiving tofacitinib without corticosteroids. Trial Registration: http://www.clinicaltrials.gov (NCT01465763[21/10/2011]; NCT01458951[21/10/2011]). [ABSTRACT FROM AUTHOR]

The approval and adoption of biosimilar products are essential to contain increasing healthcare costs and provide more affordable choices for patients. Despite steady progress in the number of the US Food and Drug Administration (FDA) biosimilar approvals over the years, biosimilar adoption in the United States has been slow and gradual, largely driven by payers rather than clinicians. In order to better understand the barriers to biosimilar adoption in the clinic, the University of Maryland Center of Excellence in Regulatory Science and Innovation (M‐CERSI) and the FDA jointly hosted a virtual workshop on April 13, 2022, titled "Biosimilars: A Decade of Experience and Future Directions – Strategies for Improving Biosimilar Adoption and the Potential Role of Clinical Pharmacology." This summary documents the experiences of four leading academic clinicians with specialties in oncology, rheumatology, gastroenterology, and endocrinology and their perspectives on how to increase biosimilar adoption, including the role of clinical pharmacology. Besides systemic changes in pricing and reimbursement, there is a need for additional education of a broad range of providers, including advanced care practitioners, and patients themselves. Educational efforts highlighting the rigor of the studies that support the approval of biosimilars—including the clinical pharmacology studies—and the benefits of biosimilars, can play a major role in improving biosimilar acceptance. [ABSTRACT FROM AUTHOR]

Purpose of review: Significant advances in the discovery of novel therapeutic targets for inflammatory bowel disease address a crucial need for patients refractory to available treatment options. We will review the recent literature and data available for novel therapies for adult patients with Crohn's disease (CD) and ulcerative colitis (UC), limited to those currently in phase III trials with a focus on clinical endpoints and safety. Recent findings: Emerging therapeutic agents currently in phase III trials including IL-23 inhibitors (risankizumab, guselkumab, and mirikizumab), JAK inhibitors (filgotinib and upadacitinib), and S1P1 modulators (ozanimod and etrasimod) are effective in the treatment of patients with moderate to severe CD and UC. Therapies with greater selectivity, including IL-23 inhibitors, have favorable safety profiles. Small molecules including JAK inhibitors and S1P receptor modulators are both orally administered and non-immunogenic. Emerging novel agents recently approved or currently in phase III trials appear to be effective and safe for the treatment of CD and UC and will expand options for medically refractory patients. Future comparative effectiveness studies and progress in precision medicine may influence therapy selection. [ABSTRACT FROM AUTHOR]

Patients with Crohn's disease (CD) or ulcerative colitis (UC) have high morbidity rates owing to debilitating intestinal complications and extraintestinal manifestations (EIMs). We retrospectively identified patients in the Truven MarketScan databases with an incident CD or UC diagnosis from January 2008 to September 2015 to quantify the incremental lifetime risk of experiencing an intestinal complication or EIM after CD or UC diagnosis. Seven intestinal complications and 13 categories of EIMs by site were identified, and lifetime risk of experiencing an intestinal complication or EIM from age at CD or UC diagnosis to end of life was estimated using parametric models. Results were compared with controls' propensity score matched by age, sex, health plan, and pre-index Charlson Comorbidity Index. The CD or UC incremental risk was calculated using the difference in rates between CD or UC patients and matched controls. A total of 34,692 CD patients and 48,196 UC patients with 1:1 matched controls were included. CD and UC patients had an increased lifetime risk of intestinal complications, which varied across ages, inflammatory bowel disease (IBD) types, and categories of intestinal complications and EIMs. CD and UC patients aged 0 to 11 years had the highest incremental lifetime risk for all 7 intestinal complications and the majority of EIMs, with blood EIMs associated with the highest incremental risk (CD: 32%; UC: 21%). CD and UC patients of all ages have a higher lifetime risk of experiencing intestinal complications and EIMs than patients without CD or UC. When evaluating the burden of disease on patients with IBD, it is important to include the burden of these intestinal complications and EIMs in the assessment. [ABSTRACT FROM AUTHOR]

Introduction: Extraintestinal manifestations (EIMs) in patients with ulcerative colitis (UC) are common. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. We evaluated the efficacy of tofacitinib in patients with EIMs, and the impact of tofacitinib on EIMs in patients with UC in the OCTAVE clinical program. Methods: Data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain) were analyzed. The effect of tofacitinib on efficacy outcomes stratified by EIM status, proportion of predefined prior and active EIMs at baseline, and change from baseline in EIMs were determined at the end of the treatment period (weeks 8 or 52), or at early termination. Results: At baseline of OCTAVE Induction 1 and 2, and OCTAVE Sustain, 27.0% and 9.0% of patients had a history of EIMs (prior or active), respectively. Patients treated with tofacitinib 10 mg twice daily (BID) achieved remission and had endoscopic improvement in all studies, irrespective of any history of EIMs. A greater proportion of patients had active peripheral arthritis at baseline of OCTAVE Induction 1 and 2 versus OCTAVE Sustain. In OCTAVE Induction 1 and 2, similar proportions of tofacitinib and placebo-treated patients with active peripheral arthritis experienced either no change (81.3% and 85.7%, respectively) or an improvement (15.6% and 14.3%, respectively). By week 52 of OCTAVE Sustain, improvements in active peripheral arthritis were only observed in tofacitinib-treated patients (16.7% and 33.3% with tofacitinib 5 and 10 mg BID, respectively). Conclusion: Any history of EIMs did not influence the efficacy of tofacitinib 10 mg BID for induction or maintenance of UC. The most common active EIM was peripheral arthritis, for which many patients in OCTAVE Induction 1 and 2, and OCTAVE Sustain, reported improvement or no change from baseline with tofacitinib treatment. Clinicaltrials.gov:NCT01465763; NCT01458951; NCT01458574 [ABSTRACT FROM AUTHOR]

Introduction: Extraintestinal manifestations (EIMs) in patients with ulcerative colitis (UC) are common. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. We evaluated the efficacy of tofacitinib in patients with EIMs, and the impact of tofacitinib on EIMs in patients with UC in the OCTAVE clinical program. Methods: Data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain) were analyzed. The effect of tofacitinib on efficacy outcomes stratified by EIM status, proportion of predefined prior and active EIMs at baseline, and change from baseline in EIMs were determined at the end of the treatment period (weeks 8 or 52), or at early termination. Results: At baseline of OCTAVE Induction 1 and 2, and OCTAVE Sustain, 27.0% and 9.0% of patients had a history of EIMs (prior or active), respectively. Patients treated with tofacitinib 10 mg twice daily (BID) achieved remission and had endoscopic improvement in all studies, irrespective of any history of EIMs. A greater proportion of patients had active peripheral arthritis at baseline of OCTAVE Induction 1 and 2 versus OCTAVE Sustain. In OCTAVE Induction 1 and 2, similar proportions of tofacitinib and placebo-treated patients with active peripheral arthritis experienced either no change (81.3% and 85.7%, respectively) or an improvement (15.6% and 14.3%, respectively). By week 52 of OCTAVE Sustain, improvements in active peripheral arthritis were only observed in tofacitinib-treated patients (16.7% and 33.3% with tofacitinib 5 and 10 mg BID, respectively). Conclusion: Any history of EIMs did not influence the efficacy of tofacitinib 10 mg BID for induction or maintenance of UC. The most common active EIM was peripheral arthritis, for which many patients in OCTAVE Induction 1 and 2, and OCTAVE Sustain, reported improvement or no change from baseline with tofacitinib treatment. Clinicaltrials.gov:NCT01465763; NCT01458951; NCT01458574 [ABSTRACT FROM AUTHOR]

Purpose of review: There is increasing demand for a personalized approach to management of patients with inflammatory bowel disease (IBD). Early prognostication and stratification of patients into distinct disease trajectories would enable treatment algorithms to be made which are less generalized and more patient-specific. We have summarized the recent medical literature and highlight the current status of precision medicine and its potential application to patients with IBD. Recent findings: Clinical characteristics, aided by serologic studies, fecal and genetic markers are commonly employed to approximate an IBD patient's future trajectory and guide therapeutic treatment decisions. More composite models that aggregate these markers have been proposed in individual studies and made available as easy to use web-based calculators, to estimate the future potential risk of need for bowel surgery, future risk of hospitalization, and development of different complications. Unique biomarkers such as metalloproteinase 3, oncostatin M, and TREM-1 have been identified which may prove useful to assist clinicians to make a choice between different biologic medications for any given patient. In addition, recent data suggest that the presence of the HLA-DQA1*05 allele may predict a higher risk for immunogenicity with anti-TNF agent monotherapy. Summary: While several biomarkers and preliminary predictive models have been proposed, additional rigorous studies in the realms of genomics, proteomics, microbiomics, and patient-reported symptoms are warranted to create more comprehensive tools which would be easily applicable in the clinical setting. [ABSTRACT FROM AUTHOR]

The last few decades of gastrointestinal (GI) endoscopy have seen phenomenal growth. In many aspects, GI endoscopy has led the field of nonsurgical interventional medicine. In many aspects, this growth is facilitated by advancements in sedation—both drugs and techniques. Unfortunately, the topic of GI endoscopy sedation is also mired in many controversies, mainly emanating from the cost of anesthesia providers. While no one debates their role in the majority of advanced endoscopic procedures, the practice of universal propofol sedation in the USA, delivered by anesthesia providers, needs a closer look. In this review, medical, political, and economic considerations of this important topic are discussed in a very frank and honest way. While such ubiquitous propofol use has increased satisfaction of both patients and gastroenterologists, there is little justification. More importantly, going by the evidence, there is even less justification for the mandated anesthesia providers use for such delivery. Unfortunately, the FDA could not be convinced otherwise. The new drug fospropofol met the same fate. Approval of SEDASYS®, the first computer-assisted personalized sedation system, was a step in the right direction, nevertheless an insufficient step that failed to takeoff. As a result, in spite of years of research and efforts of many august societies, the logjam of balancing cost and justification of propofol sedation has continued. We hope that recent approval of remimazolam, a novel benzodiazepine, and potential approval of oliceridine, a novel short-acting opioid, might be able to contain the cost without compromising the quality of sedation. [ABSTRACT FROM AUTHOR]

Background and Methods: There is an added level of complexity in the management of head and neck cancer patients with underlying immunosuppressive disorders during the COVID‐19 pandemic. Head and neck oncologists are tasked with balancing the dual risks of cancer progression in the setting of impaired tumor immunity and increased susceptibility to life‐threatening complications from exposure to viral infection for patients and providers. Through two cases of immunocompromised patients with newly diagnosed head and neck malignancies, we aim to provide guidance to clinicians struggling with how to best counsel and manage this unique subset of patients under these difficult circumstances. Results: After careful consideration of the options, we took different approaches in the care of these two patients. Conclusions: Ultimately, there is no uniform set of rules to apply to this heterogeneous group of immunocompromised patients. We provide some general principles to help guide patient management during the current pandemic. [ABSTRACT FROM AUTHOR]

As healthcare costs related to inflammatory bowel diseases (IBDs) rise, there is an increasing need to identify hospital characteristics that promote cost-effective care while minimizing adverse outcomes for this complex population. Cost effectiveness could be compared among teaching hospitals with specialized IBD physicians and surgeons, teaching hospitals without specialized IBD providers, and nonteaching hospitals. [Extracted from the article]