Real-world experience and long-term outcomes of a mandatory nonmedical switch of adalimumab originator to biosimilars in inflammatory bowel disease

BACKGROUND Over the last decade,the treatment options for inflammatory bowel disease(IBD)have significantly progressed with the emergence of new medications designed to target various immune pathways and mitigate inflammation.Adalimumab(ADA)is a tumor necrosis factor alpha antagonist and stands as an effective treatment for IBD.In April 2021,the province of British Columbia implemented a mandatory non-medical switch policy of the ADA originator Humira®to ADA biosimilars.Biosimilars offer a potential cost-effective,safe,and efficacious alternative to the originator,yet there remains limited real-world evidence on long-term outcomes of ADA non-medical switching in IBD.AIM To assess the long-term outcomes of non-medical switching from the ADA originator Humira®to an ADA biosimilar among IBD patients.METHODS A retrospective observational chart review study was conducted on IBD patients eligible for the provincially mandated non-medical switch to an ADA biosimilar.The primary outcome was treatment persistence at 30 months post-switch.Secondary outcomes included the proportion of and reasons for therapy alteration or ADA discontinuation,loss of response(LOR)rates,adverse events(AE),and clinical and biochemical remission status.Patients who remained on the originator throughout the switch period,through compassionate support or private pay,constituted the comparison group.RESULTS Patients in the originator(n=43)and biosimilar switch(n=228)groups displayed similar demographics and baseline disease characteristics.By the study endpoint of 30 months,there was no difference in the rate of treatment persistence in either group(n=36,83.7%originator group vs n=201,88.2%biosimilar group,P=0.451).Treatment persistence demonstrated similar rates of discontinuation between both study groups(log-rank P=0.543).There was a numerical but not statistically significant difference in rates of adverse outcomes between either group(39.5%originator vs 28.9%biosimilars,P=0.206).This included comparable rates of LOR(27.9%vs 17.5%)or AE(11.6%vs 11.4%)between the originator and biosimilar cohorts,respectively.C-reactive protein and fecal calprotectin levels were similar one year pre-and post-switch.CONCLUSION These data support the long-term efficacy and safety of non-medical ADA switching in IBD and will help inform patients and physicians in jurisdictions currently undergoing biosimilar switching.

FOCUS: Future of fecal calprotectin utility study in inflammatory bowel disease

AIM To evaluate the perspective of gastroenterologists regarding the impact of fecal calprotectin(FC) on the management of patients with inflammatory bowel disease(IBD).METHODS Patients with known IBD or symptoms suggestive of IBD for whom the physician identified that FC would be clinically useful were recruited. Physicians completed an online "pre survey" outlining their rationale for the test. After receipt of the test results, the physicians completed an online "post survey" to portray their perceived impact of the test result on patient management. Clinical outcomes for a subset of patients with follow-up data available beyond the completion of the "post survey" were collected and analyzed.RESULTS Of 373 test kits distributed, 290 were returned, resulting in 279 fully completed surveys. One hundred and ninety patients were known to have IBD; 147(77%) with Crohn's Disease, 43(21%) Ulcerative Colitis and 5(2%) IBD unclassified. Indications for FC testing included: 90(32.2%) to differentiate a new diagnosis of IBD from Irritable Bowel Syndrome(IBS), 85(30.5%) to distinguish symptoms of IBS from IBD in those known to have IBD and 104(37.2%) as an objective measure of inflammation. FC levels resulted in a change in management 51.3%(143/279) of the time which included a significant reduction in the number of colonoscopies(118) performed(P < 0.001). Overall, 97.5%(272/279) of the time, the physicians found the test sufficiently useful that they would order it again in similar situations. Follow-up data was available for 172 patients with further support for the clinical utility of FC provided.CONCLUSION The FC test effected a change in management 51.3% of the time and receipt of the result was associated with a reduction in the number of colonoscopies performed.

Transition clinic attendance is associated with improved beliefs and attitudes toward medicine in patients with inflammatory bowel disease

To evaluated the differences in knowledge, adherence, attitudes, and beliefs about medicine in adolescents with inflammatory bowel disease (IBD) attending transition clinics. METHODSWe prospectively enrolled patients from July 2012 to June 2013. All adolescents who attended a tertiary-centre-based dedicated IBD transition clinic were invited to participate. Adolescent controls were recruited from university-affiliated gastroenterology offices. Participants completed questionnaires about their disease and reported adherence to prescribed therapy. Beliefs in Medicine Questionnaire was used to evaluate patients’ attitudes and beliefs. Beliefs of medication overuse, harm, necessity and concerns were rated on a Likert scale. Based on necessity and concern ratings, attitudes were then characterized as accepting, ambivalent, skeptical and indifferent. RESULTSOne hundred and twelve adolescents were included and 59 attended transition clinics. Self-reported adherence rates were poor, with only 67.4% and 56.8% of patients on any IBD medication were adherent in the transition and control groups, respectively. Adolescents in the transition cohort held significantly stronger beliefs that medications were necessary (P = 0.0035). Approximately 20% of adolescents in both cohorts had accepting attitudes toward their prescribed medicine. However, compared to the control group, adolescents in the transition cohort were less skeptical of (6.8% vs 20.8%) and more ambivalent (61% vs 34%) (OR = 0.15; 95%CI: 0.03-0.75; P = 0.02) to treatment. CONCLUSIONAttendance at dedicated transition clinics was associated with differences in attitudes in adolescents with IBD.

Does training and experience influence the accuracy of computed tomography colonography interpretation?

AIM: To evaluate the effect of experience on the accuracy rate of computed tomography colonography (CTC) interpretation and patient preferences/satisfaction for CTC and colonoscopy.

Severe cholestasis due to adalimumab in a Crohn's disease patient

Elevation of liver biochemistry has been reported with anti-tumor necrosis factor agents, but overt liver failure rarely reported. Autoimmune hepatitis has been more commonly reported with infliximab than adalimumab(ADA). Our case, however, describes the first reported case of ADA-associated severe cholestatic injury. A 39-year-old female with Crohn's disease developed severe jaundice after initiation of ADA. All serologic tests and imaging studies were normal. Liver biopsy showed prominent pericentral canalicular cholestasis,without features of steatosis or sclerosing cholangitis,consistent with drug-induced cholestasis. The serum total bilirubin peaked at 280 μmol/L, and improvement was seen after 5 wk with eventual normalization of liver enzymes at 10 wk. Our case describes the first reported case of ADA-associated severe cholestatic liver disease and the first histopathologic examination of this adverse drug effect. Clinicians need to be aware of this potential drug-induced liver injury when prescribing this commonly used biologic medication.

Impact of medical therapy on patients with Crohn's disease requiring surgical resection

AIM: To evaluate the impact of medical therapy on Crohn&#x02019;s disease patients undergoing their first surgical resection.

Time of infliximab therapy initiation and dose escalation in Crohn's disease

AIM: To determine if early initiation of anti-tumor necrosis factor therapy affects the need for dose escalation.