Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres.Clinical and safety data was registered at fixed appointments. Trough levels and anti-drug antibody (ADA) concentration were measured by ELISA. Association between demographic, clinical, laboratory parameters and infusion reaction rates were evaluated statistically.Three hundred and eighty-four IBD patients were included. Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction during the treatment, 64.3% of them was previously exposed to anti TNF therapy. No infusion reaction occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients who developed infusion reaction and was switched to adalimumab in 12 patients. However in 39.3% of patients developing infusion reaction CT-P13 therapy was continued with the use of premedication. Cumulative ADA positivity rates were 8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30. Previous anti-TNF-alpha exposure (30% vs. 3.1%, p < 0.001, OR 6.3 (2.7-14.6)) and ADA positivity (32.6% vs. 4.1%, p < 0.001, OR 19(5-73)) during the induction therapy were predictive factors for infusion reactions.Patients with previous exposure to anti-TNF-alpha and ADA positivity during the induction therapy were more likely to develop infusion reactions.
The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been known for several decades, with CRC remaining one of the most feared complications. Early studies reported an excess risk of CRC in ulcerative colitis patients; however, in these reports, which were published from tertiary referral centers, patients with severe disease were over-represented. In the meta-analysis by Eaden et al. from 2001 [1], the cumulative probability of CRC in ulcerative colitis was 2 % by 10 years, 8 % by 20 years, and 18 % by 30 years. Chronic inflammation is thought to be one of the key factors in the pathogenesis, together with genetic predisposition [2].
Biological therapies have revolutionized the treatment of inflammatory bowel diseases (IBD) in the last two decades. Though biological drugs are effective, their use is associated with high costs and access to biological agents varies among countries. As the patent for the reference products expired, the advent of biosimilar monoclonal antibodies has been expected. Biosimilars represent less expensive alternatives compared to the reference product.In this review, authors will review the literature on the clinical efficacy, safety and immunogenicity of current and future biosimilar infliximabs. Short- and medium-term data from real-life cohorts and from randomized-clinical trials in IBD demonstrated similar outcomes in terms of efficacy, safety and immunogenicity as the reference product for CT-P13. Switch data from the reference to the biosimilar product are also accumulating (including the NOR-SWITCH and the CT-P13 3.4 study).The use of biosimilar infliximab in IBD is increasing worldwide. Its use may be associated with budget savings leading to better access to biological therapies and consequently improved health outcomes. Switching from the originator to a biosimilar in patients with IBD is acceptable, although scientific and clinical evidence is lacking regarding reverse switching, multiple switching, and cross-switching among biosimilars in IBD patients.
Emerging data suggest that a treat-to-target approach and early therapeutic intervention using regular objective disease assessment leads to improved outcomes. Our aim was to evaluate the value of objective disease monitoring during regular follow-up in a single tertiary inflammatory bowel disease center.Consecutive inflammatory bowel disease patients (n = 161, Crohn's disease: 118/ulcerative colitis: 43; biological therapy: 70%) were included and followed up for 1 year between January and December 2018. Data on clinical disease activity, biomarkers, endoscopy, imaging, outpatient visits, treatment optimization, hospitalization, and surgery were collected. We compared the monitoring strategy according to the clinical activity (remission/flare/post-flare/continuous activity) every 3 months (assessment period).In total, n = 644 assessment periods were evaluated. Biomarkers were evaluated in 82.9%-83.9% of patients in each assess ment period regardless of clinical activity. Colonoscopy was more frequently performed in active disease (flare/continuous disease activ ity: 21.1%/18.9% vs. clinical remission: 10.1% per assessment period). Magnetic resonance imaging was performed in 7.7%-16.7%/ period in Crohn's disease patients, while the use of computed tomography was low (2.4%/period) and mainly performed in active dis ease. Treatment optimization was more frequent in patients with active disease (biological start/dose optimization: 31.1%/33.8%/ period, steroid start: 13.2%/period). Patients with continuous activity (2.62), flare (2.45), and post-flare (2.05) had higher mean patient visit counts compared to remission (1.68/period).Objective monitoring strategy was applied with routine assessment of clinical activity and biomarkers. Fast-track colo noscopic evaluations were adapted to the clinical stage of the disease while screening colonoscopies and magnetic resonance imaging were frequently used. Objective monitoring resulted in the early optimization of medical therapy and frequent specialist follow-up visits.
Background & Aims: There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort.
Methods: 166 consecutive moderate-to-severe IBD patients (122 Crohn’s disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed.
Results: TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p<0.001). In addition, a cut-off of 14 and 17mm for TST was defined to identify IGRA positivity in a ROC analysis (AUC: 0.76, p=0.03). TST and/or IGRA positivity was not influenced by medical therapy or disease phenotype. Importantly, smoking was identified as a risk factor for TST but not IGRA positivity (OR: 2.70-5.02, p<0.01, for TSTcut-offs=5-20mm).
Conclusion: TST and IGRA tests are partly complimentary methods, and additional testing by TST (with a cut-off of >15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.– .
Abbreviations: AZA: azathioprine; BCG: Bacille Calmette-Guérin; CD: Crohn’s disease; CRP: C-reactive protein; HBI: Harvey–Bradshaw Index; IBD: inflammatory bowel diseases; IGRA: interferon-gamma release assay; IST: immunosuppressive therapy; LTB: latent tuberculosis; UC: ulcerative colitis; TB: tuberculosis; TNF: tumor necrosis factor; TST: tuberculin skin test/ Mantoux skin test
Emergency situations in inflammatory bowel diseases (IBD) put significant burden on the patient and healthcare system as well. We aimed to prospectively measure indicators of quality-of-care, after implementation of a new rapid access clinic (RAC) at the McGill University Health Centre (MUHC) tertiary care IBD centre. The RAC provides patients an opportunity to be evaluated by IBD specialists urgently without having to present to the emergency department. RAC was structured by providing an emergency contact email address to the patients, with a specific document explaining the pertinent symptoms that merit utilisation of this access avenue. Each email was read and reviewed by a specialised IBD nurse or physician. Patient access, resource utilisation and outcome parameters were collected from MUHC IBD Center Rapid Access clinic including consecutive patients who contacted the RAC via email between July 2017 and September 2018. 261 patients (44.1% men, mean age: 39 years, CD: 64% [L3: 46.2%, B2–3: 31.8%], UC: 32% [extensive colitis: 56.6%], biological therapy: 61.6%, previous surgery: 20.4%) were included. 85.7% of requests were deemed appropriate for a rapid appointment. The reason for RAC appointment was potential disease flare in 62.5% of patients. The median time to RAC visit was 3 days (IQR: 1–6 days) from the first point of contact (email/phone) by the patient. Patients had a fast track evaluation with optimised resource utilisation in the majority of cases. CRP and faecal calprotectin were the most common measures of disease severity performed, 85.2% and 62.5%, respectively. Clostridium difficile stool test and stool culture test were performed in 43.8% and 42.4% of the patients. The frequency of colonoscopy and flexible sigmoidoscopy following the RAC visit were 22.9% and 6.7%. Only a minority of patients underwent CT (7.1%) and MR (1%) imaging. A change in therapy promptly occurred in 57.0% of patients. Within 30 days from the index visit, 21 patients (19 patients with IBD-related symptoms) required ER visit and 9 patients hospital admission. 9 ER visits were initiated during the RAC visit, 7 other patients had unplanned ER visit due to continuous IBD activity. Only 5 patients who were screened by the RAC physician and deemed not to require an urgent consultation presented at the ER (unplanned ER visit rate were 1.8%, no patient required admission). Implementation of an RAC improved healthcare delivery by avoiding unnecessary ER visits and by increasing access to an IBD centre. Patients had a fast track evaluation with optimised resource utilisation. Data presented here can serve as example for a more optimal cost utilisation for future IBD centres.
