Original Title: État des connaissances: Intensification posologique des agents biologiques - gastroentérologie, rhumatologie et dermatologie

Authors' objectives: Medical associations have shared with the Ministère de la Santé et des Services sociaux (MSSS) their concerns about the need to be able to use biologics at increased dosage. These concerns appear to have been rekindled with the coming into force, in April 2021, of section 80.2 of An Act respecting prescription drug insurance and the Regulation respecting exceptions to the prohibition against paying or reimbursing the price of a medication or supply covered by the basic prescription drug insurance plan. Currently, biologics, both brand-name and biosimilars, are included in the exceptions specified in the regulation. However, the potential application of the regulation to biologics could prevent patient assistance programs from providing additional doses when clinicians deem it necessary to escalate a biologic and when its payment indication does not allow it. The MSSS has asked the Institut national d'excellence en santé et en services sociaux (INESSS) to review the literature to assess the scientific and clinical merits of biologic dose escalation in the fields of gastroenterology, rheumatology and dermatology.

Authors' results and conclusions: RESULTS: The data identified (systematic reviews and primary studies) shows that dose- escalating biologic therapies in patients who do not respond adequately to the standard dosage of their drug could restore a clinical response in approximately 50% to 60% of these patients in the different therapeutic areas. In some cases, however, this proportion may be lower or higher. The recommendations in the selected CPGs are based on these data, which are observational in nature and therefore subject to numerous biases that affect their methodological quality. The results of the studies identified generally do not raise any safety concerns, although an increased occurrence of infections cannot be completely ruled out. Studies comparing standard dosing with optimized dosing at the outset show no difference or marginal incremental benefits with optimized dosing. However, their external validity is compromised because they did not involve patients in treatment failure, which is not consistent with either the CPG recommendations advocating this approach or with clinical practice. However, it is on the basis of these studies that certain product monographs indicate that an increase in the dose or frequency of administration may be considered. It is also on the basis of these studies that coverage indications with no stipulated maximum dose have been drawn up. CONCLUSIONS: Dose escalation of biologic drugs is a practice that meets the need to individualize therapy in order to optimize efficacy. Variations in the pharmacokinetic and pharmacodynamic characteristics of biologic drugs could explain the need for dose escalation. The efficacy and safety of dose-escalating these drugs have not been evaluated in good-quality studies designed specifically for this purpose. The validity of such a practice has been established through clinical experience, which is corroborated by observational data and other publications reporting the use of such dosage adjustments. The economic impact of dose escalation is not assessed in this report. However, this practice inevitably results in a significant increase in costs, which should, ideally, be compared with the cost of complications and other consequences avoided.

Authors' methods: We conducted a rapid review of the literature to identify, among other things, clinical practice guideline (CPG) recommendations addressing inadequate response to a biologic in gastroenterology, dermatology and rheumatology. A rapid review of systematic reviews that have evaluated the efficacy or safety of biologic drugs dose escalation was carried out as well. Experiential and contextual knowledge was gathered through an invitation to comment on INESSS’s work plan and through consultations with experts, including gastroenterologists, rheumatologists and dermatologists.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/intensification-posologique-des-agents-biologiques-gastroenterologie-rhumatologie-et-dermatologie.html

Year Published: 2022

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/intensification-posologique-des-agents-biologiques-gastroenterologie-rhumatologie-et-dermatologie.html

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec