Adalimumab originator versus adalimumab biosimilars in inflammatory bowel disease in Australia.

BACKGROUND: Biosimilar adalimumabs have improved treatment access, but without any clinical advantage, distributors rely on delivery device design-enhancements, support services, and removal of painful excipients to capture market share. Prescribers, however, are often unaware of these differences. This article compares and contrasts originator versus biosimilar adalimumab agents to identify key differences that might influence adalimumab selection. RESEARCH DESIGN AND METHODS: We reviewed listed adalimumab biosimilars in Australia and compared them to the originator adalimumab. Similarities and differences identified were confirmed with the manufacturers via two rounds of interviews: the first to collate a list of features and benefits of their product, and the second to consolidate and confirm the data. RESULTS: The originator adalimumab Humira [by AbbVie, U.S.A] and four adalimumab biosimilars (Amgevita [by Amgen, U.S.A], Hadlima [by Organon, U.S.A], Hyrimoz [by Sandoz, Switzerland], and Idacio [by Fresenius Kabi, Germany]) are included in this review. Key differences identified include product formulation, dosages available, delivery devices, physician support, patient support, and the supply of other biosimilar products by the company. CONCLUSION: Adalimumab biosimilars are different from each other with unique advantages and disadvantages likely to influence prescriber and patients. Therefore, the choice of agent should be individualized to the needs of the patient and the healthcare service.

The diagnostic yield of pan-enteric capsule endoscopy in inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Capsule endoscopy (CE) is a non-invasive diagnostic modality enabling real time video imaging of the gastrointestinal (GI) mucosa. Pan-enteric capsule endoscopy (PCE) is now able to thoroughly assess the entire GI tract, including for inflammatory bowel disease (IBD). Our aim was to evaluate the diagnostic accuracy of PCEs in IBD. METHODS: We comprehensively searched electronic databases (MEDLINE, SCOPUS, EMBASE, and Cochrane Central Register of Controlled Trials) for studies comparing the diagnostic accuracy of PCE with endoscopic evaluation, intestinal ultrasound or magnetic resonance enterography (MRE). Data were analyzed by calculating forest plots and the use of the I2 statistic for heterogeneity. RESULTS: Fourteen studies were identified, with seven studies evaluating PCE diagnostic yield in Crohn's disease (CD) and seven studies in ulcerative colitis (UC). In CD, there was a trend to superiority of PCE over MRE and colonoscopy with a pooled odds ratio (OR) of 1.25 (95% CI, 0.85-1.86%) for the detection of CD. This translates to an increased diagnostic yield of 5% and 7% for PCE compared with MRE and colonoscopy, respectively. PCEs had a diagnostic sensitivity for the detection of UC of 93.8% (95% CI, 87.6-97.0%) and a specificity of 69.8% (95% CI, 38.2-89.6%). CONCLUSION: PCEs have a comparable diagnostic yield to colonoscopy and MRE in Crohn's disease. The major difficulty remains standardization of PCE scoring systems and the lack of transmural assessment. In UC, PCE has an excellent diagnostic sensitivity and positive predictive value, but there are limitations to its use including the lack of histologic assessment and poor specificity.

Recurrent Campylobacter jejuni Infection in an Immunodeficient Patient Treated with Repeated Faecal Microbiota Transplant (FMT)-A Case Report.

There is limited evidence to guide successful treatment of recurrent Campylobacter infection in patients with common variable immunodeficiency (CVID) already managed on regular immunoglobulin therapy. The role of faecal microbiota transplant (FMT) is uncertain. We report a case of recurrent Campylobacter jejuni infection in a patient with CVID treated with repeated FMT with 18 months of symptom resolution prior to relapse.

Faecal microbiota transplantation: what's beyond Clostridium difficile infection?

Over the last decade, major advancements have been made in our understanding of both the beneficial and detrimental role that microorganisms play in our innate functioning. Research into the intestinal microbiota has moved from the laboratory into our medical clinics and is being put forth as an effective therapy for a range of medical conditions, not only limited to the gastrointestinal system. The clearest example of this progression has been in the treatment of Clostridium difficile infection; however, faecal microbiota transplantation has also been shown to have a positive effect in the treatment of inflammatory disorders, such as ulcerative colitis. In this review article, we will appraise the existing literature examining the role the intestinal microbiota plays in the pathogenesis of disease and the therapeutic utility of faecal microbiota transplantation in restoring homeostasis. In many cases, these studies are in a preclinical setting, are small in scale and often are not placebo-controlled; however, the results from these studies report interesting associations between intestinal dysbiosis and disease development, as well as the beneficial effects of faecal microbiota transplantation in reversing this process.

Therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy in ulcerative colitis: results from the GO-LEVEL study.

BACKGROUND: Significant associations between serum golimumab concentrations and favourable outcomes have been observed during both induction and maintenance therapy in ulcerative colitis (UC). However, data regarding optimal therapeutic serum golimumab concentration thresholds are limited. AIMS: To identify optimal serum golimumab concentration thresholds during induction and maintenance treatment with golimumab. METHODS: GO-LEVEL was an open label, phase IV study that included a prospective cohort of UC patients commencing golimumab, as well as a cross-sectional cohort receiving maintenance treatment. Patients commencing induction for active UC (defined as a simple clinical colitis activity index [SCCAI] >5 in addition to a raised faecal calprotectin [FC] >59µg/g or, raised C-reactive protein [CRP] [>5mg/L] or, Mayo endoscopic disease activity 2 or 3) were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare or during remission. Combined clinical-biochemical remission was defined as SCCAI ≤2 and FC <250µg/g. Serum golimumab concentrations were measured using a commercially available ELISA (LISATRACKER, Theradiag). RESULTS: Thirty-nine patients were included in the induction cohort, of whom 15 (38%) achieved combined clinical-biochemical remission at week 6. The median serum golimumab concentration of those in combined clinical-biochemical remission was significantly higher than those who were not (5.0 vs 3.1 µg/mL, respectively, P = 0.03). Receiver operating characteristic (ROC) curve analysis demonstrated 3.8 µg/mL as the optimal threshold (sensitivity 0.71, specificity 0.65, area under curve [AUC] 0.72, positive predictive value [PPV] 0.59 and negative predictive value [NPV] 0.79). Sixty-three patients were included in the maintenance cohort; 31 (49%) were in combined remission, 32 (51%) were not. The median serum golimumab concentration of those in combined remission was significantly higher (2.9 vs 2.1 µg/mL, respectively, P = 0.01). ROC curve analysis demonstrated 2.4 µg/mL as the optimal threshold (sensitivity 0.68, specificity 0.66, AUC 0.68, PPV 0.65 and NPV 0.66). CONCLUSIONS: GO-LEVEL (NCT03124121) offers further evidence regarding golimumab's exposure-response relationship. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested therapeutic thresholds of 3.8 µg/mL at week 6 and 2.4 µg/mL during maintenance.

Effectiveness of vedolizumab dose intensification to achieve inflammatory bowel disease control in cases of suboptimal response.

BACKGROUND: Despite the proven efficacy of vedolizumab (VDZ) for ulcerative colitis (UC) and Crohn's disease (CD), suboptimal response is commonly encountered. However, data regarding the effectiveness of dose intensification (by interval shortening) to achieve response are limited. OBJECTIVES: We evaluated the effectiveness of dose intensification at achieving response in patients with a previously suboptimal response to VDZ. Additionally, we aimed to identify predictors of response to this strategy. METHODS: We performed a retrospective cohort study of patients who underwent VDZ dose intensification for suboptimal response. Clinical disease activity was evaluated at the point of dose intensification (baseline) and at weeks 12 and 24. Response was defined as Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) reduction of ≥3, and remission as HBI <5 or SCCAI <3. RESULTS: A total of 36 patients received dose intensification to 4-weekly infusions: 18 CD, 14 UC and 4 inflammatory bowel disease-unclassified (analysed in the UC group). Median SCCAI scores fell from 6 (range 0-11) at baseline to 4 (0-6, p=0.008) at week 24, while HBI scores did not change significantly (4 (0-27) and 3 (0-8), p=0.092). Overall median C reactive protein (CRP) fell from 6 mg/L (1-23) to 2 mg/L (1-17, p=0.011). Of 20 patients with clinically active disease at baseline, 10 (50%) responded, of whom 4 (20%) achieved remission at week 24. Univariate analysis demonstrated low baseline CRP (p=0.045) and response at week 12 (0.020) were associated with week 24 response. CONCLUSIONS: Our findings demonstrate VDZ dose intensification to be effective at achieving clinical response in half of patients. Low baseline CRP and response at week 12 are potential predictors of week 24 response.

Faecal microbiota transplantation for refractory C lostridium difficile infection.

Faecal microbiota transplantation (FMT) has become a part of the treatment algorithm for Clostridium difficile infection (CDI), particularly for recurrent infections when antibiotics have diminishing efficacy. Notably, despite a significant proportion of patients suffering from refractory disease, there is a general lack of evidence describing the use of FMT in this patient cohort. We present here a case of successful treatment of refractory CDI in a patient under critical care.

Recent advances in monoclonal antibody therapy in IBD: practical issues.

The advent of monoclonal antibody therapies has revolutionised inflammatory bowel disease (IBD) treatment and delivered great benefits to patients. The optimal use of this class of drugs requires careful management and a clear understanding of their properties. In this review article, we consider how to maximise the benefit of our most novel biological agents, vedolizumab and ustekinumab. For each agent, we consider practical aspects including dose flexibility, evidence for use in combination with a conventional immunomodulator and the potential role of therapeutic drug monitoring. We also address positioning of the various mechanisms and agents in treatment algorithms as well as important aspects of managing patients receiving monoclonal antibodies, such as disease reassessment. Finally, we look ahead to the future of monoclonal antibodies, where not only have biosimilars increased the number of agents available but there are also a range of novel mechanisms currently in late phase clinical trials.

Biologic therapies for Crohn's disease: optimising the old and maximising the new.

The era of biologic agents for the treatment of Crohn's disease has brought about significant benefits for patients, and since the introduction of infliximab at the turn of the century, the entire field has moved on rapidly. Clinicians now have multiple agents at their disposal and a choice between several different anti-inflammatory mechanisms of action. This has allowed unprecedented improvements not only in symptoms and quality of life for patients previously refractory to conventional treatments but also for demonstrated healing of the intestinal mucosa and resolution of perianal fistulation. However, despite the undisputed efficacy of these agents, there remains a significant proportion of patients who fail to gain a meaningful benefit. Through years of studying infliximab and its counterpart anti-tumour necrosis factor (anti-TNF) agent, adalimumab, we now understand that strategies such as combining use with a conventional immunomodulator or measuring serum levels can help to optimise outcomes and reduce the proportion of patients for whom treatment fails. Work is ongoing to understand whether these principles apply to newer biologics such as vedolizumab and ustekinumab. In addition, novel approaches are being investigated in an attempt to maximise the benefit that these agents could offer. In this article, we summarise these new understandings and consider ways in which they could be integrated into clinical practice for the benefit of patients.

Positioning biologics and new therapies in the management of inflammatory bowel disease.

PURPOSE OF REVIEW: Since the advent of anti-tumour necrosis factor agents, knowledge of their optimal use and their pitfalls has grown exponentially. However, the range of therapeutic agents available to clinicians and patients is expanding, creating challenging decisions about which drugs to use at any given time point. The present review aims to provide a framework within which positioning decisions can be made in the context of limited comparative effectiveness data. RECENT FINDINGS: The present review will summarize the current literature emphasizing how best to use biologic agents, and will provide suggestions as to how they should be positioned. Recent trials comparing efficacy and safety will be considered as will their strengths and weaknesses. SUMMARY: On reading this review, clinicians should have an understanding of the optimal use of currently approved biologic agents and tofacitinib and how they might be positioned in relation to one another.