Expert review of clinical immunology
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Expert Rev Clin Immunol · Jan 2015
ReviewScientific rationale behind the development and approval of biosimilar infliximab (CT-P13) in Europe.
Biosimilars are drugs developed to be highly similar to their originator biologic (or 'reference medicinal product') with no clinically meaningful differences in purity, efficacy or safety. Production of biologics and biosimilars is highly complex and sensitive, with any change in manufacturing process having a potential impact on efficacy and safety. ⋯ The scientific rationale underlying the regulatory comparability exercise for process-changed reference medicinal products and biosimilars is also discussed, as is the issue of 'switchability' from a reference medicinal product to its biosimilar. CT-P13 (Remsima(®), Inflectra(®)), a biosimilar of infliximab, is used as a case study to discuss these issues.
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Expert Rev Clin Immunol · Jan 2015
ReviewThe histiocytosis Erdheim-Chester disease is an inflammatory myeloid neoplasm.
Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis, characterized by the infiltration of tissues by foamy CD68(+)CD1a(-) histiocytes. (99)Technetium bone scintigraphy revealing almost constant tracer uptake by the long bones is highly suggestive of ECD, and a 'hairy kidney' appearance on abdominal computed tomography scan is observed in about half of all ECD cases. CNS involvement is a strong prognostic factor and independent predictor of death. IFN-α seems to be the best initial treatment for ECD. ⋯ More than 30 patients worldwide harboring this mutation and displaying multisystemic, refractory ECD have been treated with vemurafenib, a BRAF inhibitor, which has proven highly beneficial. Other recurrent mutations of the MAPK and PIK3 pathways (NRAS, PIK3CA) have recently been described. These mutations should lead to a new classification of histiocytic disorders such that Langerhans cell histiocytosis and ECD are classified as inflammatory myeloid neoplasms.
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Expert Rev Clin Immunol · Jan 2015
ReviewCurrent treatment recommendations and considerations for cryopyrin-associated periodic syndrome.
Cryopyrin-associated periodic syndrome (CAPS) encompasses a spectrum of three phenotypes of increasing severity. The syndrome is due to dominant mutations in NLRP3, which encodes a key component of the innate immunity that regulates the secretion of IL-1β. ⋯ They have acceptable safety profiles but do have some differences. We review three drugs that are currently marketed for CAPS, give additional information for the practical use of these drugs, and provide some recommendations for management.
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Although three sublingual immunotherapy tablets have been approved in the USA and more are under study, it is not clear that sublingual immunotherapy tablets will answer the needs of many patients in the USA, and this is due to the limited number of allergens that will be offered. Alternatives that employ off-label, currently available extracts hold the greatest likelihood of entering the US allergy practice. Those approaches that employ recombinant technology to produce hypoallergenic products face a long and expensive pathway to approval. Which of the many approaches under study will make it to the market is presently not clear.
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Expert Rev Clin Immunol · Jan 2015
Management of polysensitized patient: from molecular diagnostics to biomolecular immunotherapy.
A panel of Italian allergists gathered to discuss the issue concerning the management of polysensitized patients. The main conclusions were as follows: polysensitization is a relevant clinical characteristic as it affects about 70-80% of the global allergic population; the diagnostic pathway needs the use of an adequate and thorough methodology, based on the demonstration of consistency between history and documented sensitization; polysensitization and polyallergy are not synonymous: true allergy should always be demonstrated; polysensitization does not constitute a limitation to allergen immunotherapy prescription, as 1-2 allergen extracts could be effective in polysensitized patients; the allergen immunotherapy product characteristics should include the following: high efficacy and optimal safety profile, standardized production, and documented presence and titration of the major allergen.