BACKGROUND:Infliximab's efficacy as a second-line agent in moderate or severe ulcerative colitis after prior advanced therapy failure is unclear. Registration trials for infliximab did not assess its efficacy after exposure to other advanced therapies, a sequence in which it is increasingly used. We evaluate infliximab's second-line effectiveness, identify predictors of response, and compare outcomes to its first-line use. METHODS:We conducted a retrospective cohort study of adults with ulcerative colitis treated with infliximab at a tertiary care center. Patients were categorized by line of therapy. Clinical and endoscopic outcomes at 1 year were compared between first-line and second-line users. Multivariable logistic regression was used to assess predictors of 1-year clinical remission. RESULTS:Among 225 included patients, 143 received infliximab first-line and 82 as second-line or subsequent therapy. Clinical response at 1 year was significantly lower in second-line users (odds ratio 0.53, 95% confidence interval: 0.28-0.99, P  = 0.049) and remained significantly lower after adjustment for biosimilar and concurrent steroid use. Dose escalation was more common with second-line use (57.3% vs. 42.0%, P  = 0.026). Endoscopic and histologic remission was numerically lower in second-line users (47.7% vs. 33.3% and 27.0% vs. 41.7%, respectively), though these were not statistically significant ( P  = 0.180 and 0.099, respectively). CONCLUSION:Infliximab remains effective as a second-line agent in ulcerative colitis, though with reduced response and higher rates of dose escalation as compared to use first-line. These findings support its continued use while highlighting the need for optimized patient selection and treatment strategies in therapy-exposed populations.

Background and Goals: The role of early proactive therapeutic drug level monitoring for anti–tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes. Materials and Methods: This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR. Results: Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P=0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P=0.11). Conclusions: Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.

Abstract Background Transitioning from pediatric to adult health care is associated with significant psychosocial and clinical morbidity. Adolescents not only transition their medical care, but also experience vast changes in the physical, social, and psychological spheres of their lives. The medical team must help navigate these changes to provide optimal care. IBD in adolescence is associated with increased hospitalizations and surgery. This is due to several factors, including medication non-adherence and a failure to attend medical appointments. There has been a greater focus on improving care for this unique population. McMaster Children’s Hospital has integrated the AYA IBD clinic for patients between the ages of 16 and 22. The goal is to transition patients using a developmentally appropriate framework to facilitate self-efficacy and help identify comorbid mental health conditions while building resilience. Aims To explore the impact of the implementation of a dedicated transition clinic on attendance at medical visits for AYA patients with IBD. Methods The total numbers of patients booked in the AYA IBD Clinic was compared to an age matched subset of the patients in the adult McMaster Complex IBD (CIBD) Clinic. These visits were assessed based on whether the visit was: attended, cancelled, or no showed. Visits were then stratified between in-person and virtual visits. Unpaired t tests was performed to compare the AYA IBD clinic and the CIBD clinic. Findings were deemed significant based on p-values <0.05. Results The percentages of patients that attended visits (in-person or virtually) was similar between both clinics at 86% versus 79% Year 1 (Y1) and 76% versus 81% Year 2 (Y2). The number of patients seen in the AYA clinic increased from Y1 (n=92) to Y2 (n=131). The CIBD clinic saw fewer patients between Y1 (n=202) and Y2 (n=79). There were a higher number of patients who cancelled or no showed in Y2 versus Y1 for the AYA virtual visits (13 versus 8) compared to the CIBD clinic (Y2,1 versus Y1,1). Conclusions Our results highlight the challenges of transitioning adolescent patients with IBD. Our retrospective study was not powered to show significance. Given the increase in cancellation and no-show rates in Y2, the AYA clinic has incorporated a patient navigator to issue reminder phone calls and facilitate communication with patients between clinics. Future studies will re-assess how the presence of a patient navigator impacts attendance and cancellation rates. Future studies will also assess how the AYA clinic impacts transition readiness and self-efficacy, which is being measured through validated questionnaires in our clinic. Funding Agencies Grants-In-Aid

PURPOSE:Inflammatory bowel disease (IBD) significantly impacts patients' quality of life and imposes a considerable psychological, social, and financial burden. While the relationship between disease activity and quality of life is well established, the subjective challenges of living with IBD are more difficult to assess, and suggestions for improving patient experiences are lacking. The aim of this paper was to explore the various challenges patients encounter in living with IBD and to propose suggestions for overcoming them.PATIENTS AND METHODS:This study utilized a qualitative descriptive design with thematic content analysis. Patients were recruited from the Gastroenterology Clinic at McMaster University Medical Centre from December 2014 to April 2015. Data were collected over the course of 5 focus group interviews using a semi-structured interview guide.RESULTS:Seventeen patients aged 25 to 77 years old (mean age 43 years, SD 17 years) were interviewed. Fifteen patients were diagnosed with Crohn's disease and 2 patients were diagnosed with ulcerative colitis. Findings were categorized into 18 subthemes which were grouped into 4 broader themes: awareness factor, psychosocial impacts, financial burden, and quality of care.CONCLUSION:IBD is associated with complex personal challenges across various demographics. Identifying and meeting the unique needs of individual patients may be achieved through improving communication between patients and their healthcare providers. Family-based education approaches, individualized psychotherapy with therapists familiar with IBD, awareness initiatives addressed to important stakeholders, and patient involvement in community support groups may improve overall IBD care.

BackgroundFecal microbiota transplantation (FMT) is a promising experimental therapy for ulcerative colitis (UC), yet patient acceptance remains poorly understood.AimsThe aim of this study was to explore perceptions and experiences of adult patients who received FMT for UC.MethodsThis study used a qualitative descriptive design with thematic content analysis. Patients who were approached for enrollment in a clinical trial (NCT02606032) were invited to participate in face-to-face semistructured interviews. Two groups were interviewed: those who chose to pursue FMT and those who declined FMT. Non-FMT patients were interviewed once; FMT patients were interviewed twice at pre- and post-treatment.ResultsNine FMT patients (78% female, average age 46.7 years old) and eight non-FMT patients (50% female, average age 39.5 years old) were enrolled. Pretreatment themes included FMT as a natural therapy, external barriers to pursuing FMT, concerns with FMT and factors influencing the decision to pursue FMT. While both groups generally perceived FMT as a natural therapy, pre-FMT patients showed greater acceptance of alternative medicine. Both groups demonstrated poor understanding and similar initial concerns with product cleanliness. Pre-FMT patients were motivated to pursue FMT by feelings of last resort. Post-FMT themes included therapeutic impact of FMT and psychosocial impact of FMT. Post-FMT patients reported overall satisfaction and a unanimous preference for FMT over conventional medications.ConclusionThis is the first study to assess adult patient perceptions and real-life experiences with FMT for the treatment of UC. By improving patient education, we may achieve greater acceptance of FMT.

Background The aim of this study was to examine the associations among depression, anxiety and health-related quality of life and predictors of improvement of quality of life in patients with inflammatory bowel disease. Methods This was a prospective cohort study conducted in the gastroenterology clinic at McMaster University Medical Center in Hamilton, Ontario, Canada from May 2014 to March 2015. We included 60 adult patients above the age of 18 years old with a diagnosis of inflammatory bowel disease. We assessed anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and Health Related Quality of Life (HRQoL) using the Short Inflammatory Bowel Disease questionnaire (SIBDQ) at baseline and after 6 months. Linear regression was performed to estimate the associations among depression, anxiety and predictors of improvement in health-related quality of life. Results The anxiety scores decreased over the span of 6 months (median HADS-A baseline 9.00 [interquartile range {IQR} 6 to 12], and median HADS-A 6 months 7.00 [IQR 3.75 to 7.00]). There was a moderate negative correlation between anxiety (baseline r = -0.510, and 6-month r = -0.620; P < 0.001), depression (baseline r = -0.630, and 6-month r = -0.670; P < 0.001) and HRQoL scores. Using a multivariate linear regression model, elevated HADS score were associated with lower SIBDQ scores at baseline (Beta coefficient -0.696 [95% confidence interval {CI} -1.51 to -0.842]; P < 0.001). Lower SIBDQ score at baseline predicted decreased SIBDQ at 6 months (Beta coefficient 0.712 [95% CI 0.486 to 1.02]; P < 0.001). Conclusion Anxiety and depression are frequently seen in inflammatory bowel disease patients and lead to poor HRQoL. Psychological comorbidities may contribute to maladaptive behaviours and difficult disease management.

Abstract Background Corticosteroids (CS) have been used extensively to induce remission in Crohn’s disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. Aim The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN Methods The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. Results A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. Conclusion The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

INTRODUCTION: ABP 710 (US: AVSOLA™ [infliximab-axxq]) is an approved biosimilar to infliximab reference product (RP). The primary mechanism of action (MOA) of infliximab RP is mediated by binding to soluble tumor necrosis factor (TNF) alpha, inhibiting its proinflammatory signaling. Secondary mechanisms mediated by binding to membrane bound (mb) TNF alpha may play a role in inflammatory disease as demonstrated by reverse signaling, mixed lymphocyte reactions (MLRs) and effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity. Here we examined specific ex-vivo functional studies to support extrapolation of ABP 710 to Crohn’s disease (CD). METHODS: Fecal calprotectin (FCal) levels were measured by ELISA and phenotyping of peripheral blood mononuclear cells (PBMCs) was carried out in healthy volunteers and in patients with CD by flow cytometry. ADCC was assessed in PBMCs isolated from 5 healthy volunteers and 3 patients with CD. Multiple lots of ABP 710 and RP sourced from the United States (US) and the European Union (EU) were compared for ADCC. RESULTS: FCal levels were higher in patients with CD as compared to control and were also higher in patients with CD with higher baseline levels of C-reactive protein (CRP). Peripheral blood immunophenotyping of patients with CD also demonstrated that most immune cell (granulocytes, lymphocytes, natural killer cells and monocytes) markers were similarly higher in patients with CD and with high CRP as compared to control (see Table). As with FCal, higher baseline CRP was associated with an increase in blood immune markers. ADCC data from PBMCs isolated from 5 healthy volunteers and 3 CD patients demonstrated similar function in ABP 710 as compared with the RP (US and EU) in all samples from healthy volunteers and in 2 out of 3 samples from patients with CD. CONCLUSION: ABP 710 infliximab RP biosimilar has previously been shown to be highly similar to the RP in efficacy, safety and immunogenicity. We have demonstrated that similarity extends to biological activity across key MOAs, including those mediated through mbTNF alpha which may be important for the efficacy of infliximab in patients with CD. Coupled with previously reported analytical similarity assessments, similar ex vivo ADCC activity in PBMCs isolated from healthy volunteers and patients with CD despite differences in physiological and blood phenotype indicators, contribute to the totality of evidence supporting efficacy of ABP 710 in CD.Table 1

Abstract Background Faecal microbiota transplantation (FMT) is widely being studied for its therapeutic efficacy for a variety of ailments. Despite its gaining popularity, there is a limited understanding of firsthand patient experiences. We explored perceptions of patients who chose to pursue FMT and patients who declined FMT in favour of conventional medications for the treatment of their ulcerative colitis (UC). Methods Using qualitative descriptive design, eligible patients were invited to participate in face-to-face semi-structured interviews before and after FMT treatment. Interviews were audiotaped, transcribed, and analysed using a thematic analysis. Results Main baseline themes across the FMT (n = 9) and non-FMT (n = 8) groups included: (i) knowledge of FMT, (ii) attitudes around FMT, and (iii) factors contributing to the decision to pursue FMT. Post-FMT themes included: (i) experiences with FMT, and (ii) perceived response to treatment. We found a poor general understanding of FMT across both cohorts, suggesting a need for improving patient education. Non-FMT patients were less likely to have heard or researched FMT in the past due to feelings of ‘it just sounds weird’. Similar concerns were found across both groups, including fear of transmissible infections, cost of experimental therapy, and aversion to stool. Expectations varied between the two groups, with feelings of hope and a sense of ‘last resort’ driving patients to pursue FMT. In contrast, the non-FMT cohort felt a need to further research FMT, explore other treatment options before committing to FMT, and were more likely to describe their disease activity as ‘not at the severe end’. This demonstrates that FMT may be perceived as a ‘last-ditch effort’. Despite initial aversion, the non-FMT group demonstrated an interest in learning more about FMT and felt more open to the possibility of pursuing FMT in the future. The FMT group was more likely to harbour a positive view of natural medicine and classify FMT as natural, while the non-FMT cohort expressed ‘I’m not really into the weird stuff’. Post-FMT, some patients expressed delight in the perceived changes in their symptoms, including improved quality of life, decreased urgency, and less concerns with accidents. Conclusion Our results suggest that important motivating factors for pursuing FMT are a perception of naturality and a sense of last resort. With improved education, FMT may pose an acceptable and tolerable treatment option for patients with UC.

Abstract Aims The relationship between the age of diagnosis of inflammatory bowel disease (IBD) and adverse disease outcomes has not been well defined. This study aims to determine whether an early age of diagnosis is associated with worse disease outcomes. Methods This was a retrospective study of IBD patients seen at McMaster University Medical Centre, in Hamilton, ON, Canada from 2012 to 2018. Patients were classified as having poor outcomes if they had any of the following: (1) two or more bowel resections since diagnosis; (2) two or more hospitalizations for disease exacerbation since diagnosis; or (3) more than three months of corticosteroid use within 24 months of diagnosis. Prior knowledge in combination with forward selection was used to develop a multivariate logistic regression model and identify predictors of poor IBD outcomes. The variables used in the forward selection model included age at diagnosis (less than vs. greater than 25), smoking status, sex, disease duration, and type of IBD. Results A total of 617 IBD patients were included in the analysis, of which 356 (57.7%) had Crohn’s disease, 234 (37.9%) had ulcerative colitis, and 27 (4.4%) had IBD-U. The median age at diagnosis was 25 (interquartile range (IQR) 17–37). Median disease duration was 16 years (IQR 11–24). A univariate regression analysis indicated that the odds ratio (OR) of poor outcomes was found to be 0.55 (0.38 - 0.79) for those ≥25 years of age compared to to those <25. In the multivariate regression analysis (Table 1), all of disease duration, smoking status, and IBD type were found to have a significant association with having poor outcomes. Each year of disease duration was associated with an increase in odds of poor outcomes (OR 1.06, 95% CI 1.03–1.09). Active smokers had increased odds of poor outcomes compared to past or never smokers (OR 5.01, 95% CI 1.71–14.68). Patients with ulcerative colitis were less likely to experience poor outcomes compared to Crohn’s disease patients (OR 0.38, 95% CI 0.24–0.57). Age of diagnosis was no longer found to have a significant association with poor outcomes, once adjusted for other co-variates (OR 0.74, 95% CI 0.47–1.15). Conclusions Age of diagnosis was not found to have a relationship with occurrence of poor IBD outcomes, after adjustment for co-variates. However, patients with increased disease duration, active smoking status, and Crohn’s disease (compared to UC) were found to have increased odds of poor IBD-related outcomes. Funding Agencies None

Abstract Background Ustekinumab is a monoclonal antibody against the p40 subunit of IL-12 and IL23 which has been proven efficacious and safe in clinical trials, yet, real-word effectiveness studies are lacking. We aimed to determine the effectiveness and safety of ustekinumab in Crohn’s disease patients in a usual care setting, as well as to identify factors that predict response to treatment. Methods This was a retrospective review of patients with Crohn’s disease who had received ustekinumab at McMaster University Medical Center between January 2017 and August 2019. The primary endpoints were 12-month rates of clinical response, clinical remission and endoscopic improvement (according to physician assessment). We also performed a multivariate logistic regression to determine independent predictors of treatment effectiveness. Key safety outcomes were rates of adverse events including infections. Results We included 123 patients with Crohn’s disease, 58.8% of which had ileocolonic disease. Of these patients, 79.5% had prior TNF-antagonist exposure and 17.1% had previously used vedolizumab. The 12-month rate of clinical response, clinical remission, and endoscopic improvement, were 88%, 35%, and 47% respectively. On univariable analyses, longer disease duration was associated with a lower likelihood of achieving endoscopic improvement (OR 0.91 per year of disease duration, 95% CI 0.84–0.99, p = 0.03). On multivariate logistic regression, concomitant steroid use (OR 0.34, 95% CI 0.12–0.99, p = 0.049) and previous vedolizumab exposure (OR 0.13, 95% 0.02–0.77) were significantly associated with less likelihood of achieving clinical response at 12 months. Adverse events occurred in 13% of patients and infections occurred in only 1% of patients. Conclusion Ustekinumab has been effective in our real-world experience at achieving clinical response, clinical remission and endoscopic improvement in patients with Crohn’s disease. We found that concomitant steroid use and prior vedolizumab exposure were associated with a lower likelihood of clinical response. Further prospective data are needed to understand whether these are truly predictors of lack of response, or represent confounding from patients with more refractory disease.

Abstract Background This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD). Methods We recruited adult IBD patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared the results of the patient’s biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC). Results We found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation. Conclusions These results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.

Background3 classes of biologics are now available for the treatment of Crohn's disease. The availability of multiple treatment options has led to questions regarding the appropriateness of each agent for a given patient. We aimed to evaluate physician preferences for the use of specific biologic agents in a variety of Crohn's disease management scenarios using the RAND/UCLA Appropriateness Methodology.MethodsA panel consisting of members of the CINERGI group (Canadian IBD Network for Research and Growth in Quality Improvement) was assembled. A literature review was performed on factors identified as influential upon choice of biologic therapy. Clinical scenarios were developed, and panelists rated the appropriateness of biologic therapy classes in each scenario individually and again during a face-to-face meeting after moderated discussion.ResultsTwo hundred eighty-eight modifications of 3 clinical scenarios were rated. Factors that influenced biologic choice included perianal disease, antidrug antibody status, extraintestinal manifestations, consideration of potential pregnancy, and history of serious infection or malignancy. Anti-TNF therapy was considered appropriate in the postoperative patient. Ustekinumab and vedolizumab were considered appropriate in patients without perianal disease over the age of 65 with a history of malignancy or serious infection. The use of anti-TNF therapy was considered inappropriate in some scenarios whereby drug level was adequate and no antidrug antibody (ADA) was detectable.ConclusionsWe evaluated the appropriateness of the 3 available classes of biologics in a number of scenarios for the treatment of Crohn's disease. History of serious infection and malignancy, particularly in individuals over 65 years, and consideration of future pregnancy were patient-specific variables that impacted treatment decisions. These findings can serve as a guide for providers considering biologic therapy in patients with Crohn's disease.10.1093/ibd/izy333_video1izy333.video15850922807001.

BACKGROUND: Fecal microbiota transplantation (FMT) is becoming popular treatment option for a variety of diseases, including ulcerative colitis (UC). Despite increasing evidence for its role as a therapeutic, currently available literature is limited in its scope to assess firsthand patient experiences. We explored perceptions, attitudes, and experiences of patients who chose to pursue FMT and patients who declined FMT in favor of conventional medications. METHODS: This study used a qualitative descriptive design, embedded within a larger randomized controlled trial (RCT) of adult patients diagnosed with UC enrolled in accessing efficacy of FMT (NCT02606032). Patients were invited to participate in face-to-face semi-structured interviews before and after treatment. Perceptions about FMT were compared to patients who were eligible to participate in the RCT but chose to pursue conventional medications. Interviews were audiotaped, transcribed, and analyzed using thematic analysis. RESULTS: We interviewed 9 patients who underwent FMT treatment and 8 patients who declined FMT treatment. The main themes across the two groups at baseline included: (i) knowledge of FMT, (ii) attitudes around FMT, and (iii) factors contributing to the decision to pursue FMT. Post-FMT, prominent themes included: (i) experiences with FMT, and (ii) perceived response to treatment. We uncovered a poor general understanding of FMT across both cohorts of patients, suggesting a need for improved patient education. Compared to FMT patients, non-FMT patients were less likely to have heard or researched FMT in the past due to feelings of “it just sounds weird”. Similar hesitations with FMT were felt across both groups, including fear of transmissible infections, cost of commitment to an experimental therapy, and inherent aversion to stool. Expectations of FMT varied between the two groups, with feelings of hope in the treatment and a sense of “last resort” driving patients to pursue FMT. In contrast, the non-FMT cohort felt a need to further research FMT and explore other treatment options before committing to FMT and were more likely to minimise their disease activity as “not at the severe end”. This demonstrates that FMT may be perceived as a “last ditch effort” for many patients. Despite initial aversion, the non-FMT patients demonstrated interest in learning more about FMT and expressed having felt more open to the possibility of pursuing FMT in the future. Those that underwent FMT viewed FMT as a natural treatment and were more eager to explore alternative medicine in comparison to the non-FMT cohort who expressed “I’m not really into the weird stuff”. Post-FMT, some patients expressed delight in the perceived change in their symptoms, voicing an improved quality of life, decreased bowel urgency, and less concerns with soiling accidents. CONCLUSION(S): We explored perceptions and experiences with FMT in UC patients who chose to pursue FMT to patients who declined FMT for conventional treatments. While many of the pre-FMT perceptions are comparable across the two groups, important motivating factors in favor of FMT appears to be a perception of naturality and a last resort option. These results suggest that with improved education, FMT may pose an acceptable and tolerable treatment options for patients with UC.

ABP 501 (EU: AMGEVITA® [adalimumab]; US: AMJEVITA™ [adalimumab-atto]) is the first approved biosimilar to adalimumab (HUMIRA®). The primary mechanism of action (MOA) of adalimumab is mediated by binding to soluble tumour necrosis factor (TNF)-α, inhibiting its proinflammatory signalling. Secondary mechanisms mediated by binding to membrane bound (mb) TNF-α may play a role in inflammatory bowel disease (IBD) and include reverse signalling, mixed lymphocyte reactions (MLRs) and effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). To support extrapolation to IBD, specific ex vivo functional studies explored the similarity of ABP 501 to adalimumab reference product (RP) in these mechanisms. Multiple lots of ABP 501 and RP sourced from the USA (US) and the European Union (EU) were compared. Binding of ABP 501 and RP to soluble TNF (sTNF) α and mbTNF α were tested. Blocking of TNF α-induced caspase activation, IL-8 secretion and lymphotoxin (LT)-α (TNF-β) bioactivity (ie, specificity) were also assessed. To confirm similarity in Fc-mediated functions, ADCC using engineered NK92 cells expressing the high-affinity variant of FcgRIIIa (158V) and CDC were tested. ADCC was also assessed in peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers and patients with Crohn’s disease. Relative binding to sTNF α was similar [ABP 501, 108%; RP (EU), 111%; RP (US), 112%], demonstrating similarity in potency. Relative binding to mbTNF α was also similar [ABP 501, 103%; RP (EU), 106%; RP (US), 105%]. Relative activity in reverse signalling was similar [ABP 501, 99%; RP (EU), 99%; RP (US), 98%]. Relative activity was similar in NK92 ADCC [ABP 501, 85%; RP (EU), 87%; RP (US), 86%] and CDC [ABP 501, 100%; RP (EU), 94%; RP (US), 94%]. PBMCs isolated from healthy volunteers and patients with Crohn’s disease showed similar, dose-dependent ADCC activity with all three agents. ABP 501 adalimumab biosimilar has previously been shown to be highly similar to adalimumab RP in several analytical assessments, clinical pharmacokinetics, efficacy, safety and immunogenicity. We have demonstrated that similarity extends to biological activity across key MOAs, including those mediated through mbTNF-α that may be important for the efficacy of adalimumab in IBD. Coupled with previously reported effector function and reverse signalling assessments, ex vivo ADCC activity in PBMCs isolated from healthy volunteers and patients with Crohn’s disease contribute to the totality of evidence supporting efficacy of ABP 501 in IBD.