Biosimilar Monoclonal Antibodies: Considerations for Gastroenterologists

Background and primary objective: The first biosimilar of the tumor necrosis factor-alpha inhibitor infliximab has been approved in multiple countries. Indication extrapolation was a key area in which regulatory decisions differed. This review provides an overview of biosimilarity, and discusses approaches to indication extrapolation, issues relating to immunogenicity, and clinical implications for gastroenterologists. Procedures: This was a narrative review of regulatory guidelines related to biosimilar products with a focus on indication extrapolation, immunogenicity, and clinical implications for gastroenterologists. Discussion and conclusions: Biosimilarity is established with comprehensive quality comparisons followed by comparative nonclinical and clinical studies. Differences identified during the quality comparison may have clinical implications and must be investigated. Although comparative analytical data provide the foundation for use of a biosimilar for the specific indication(s) tested, additional factors must be considered when determining the appropriateness of indication extrapolation. Current abbreviated regulatory processes are facing challenges about the indication extrapolation of complex biologics such as monoclonal antibodies, particularly when there are potential differences in disease pathogenesis and safety and immunogenicity profiles between the target populations/indications. Particularly relevant to gastroenterologists is whether clinical study data in rheumatologic diseases, taken together with the analytical and preclinical data, form an adequate basis for approval of a biosimilar in inflammatory bowel disease-related indications. The results of ongoing studies of biosimilar infliximab in patients with inflammatory bowel disease are anticipated to help to better inform clinical decisions regarding this product

Algorithm for Identification of Undifferentiated Peripheral Inflammatory Arthritis: A Multinational Collaboration Through the 3e Initiative

To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA). An algorithm for identification of UPIA was developed by consensus during a roundtable meeting with an expert panel. It was informed by systematic reviews of the literature used to generate 10 recommendations for the investigation and followup of UPIA through the 3e initiative. The final recommendations from the 3e UPIA Initiative were made available to the panel to guide development of the algorithm. The algorithm drew on the clinical experience of the consensus panel and evidence from the literature where available. In patients presenting with joint swelling a thorough evaluation is required prior to diagnosing UPIA. After excluding trauma, the differential diagnosis should be formulated based on history and physical examination. A minimum set of investigations is suggested for all patients, with additional ones dependent on the most probable differential diagnoses. The diagnosis of UPIA can be made if, following these evaluations, a more specific diagnosis is not reached. Once a diagnosis of UPIA is established, patients should be closely followed as they may progress to a specific diagnosis, remit, or persist as UPIA, and additional investigations may be required over time. Our algorithm presents a diagnostic approach to identifying UPIA in patients presenting with joint swelling, incorporating the dynamic nature of the condition with the potential to evolve over tim