モノクローナル抗体製剤における治験時除外基準と市販時禁忌項目の相違点の実態調査

抄録

Objective: In clinical settings, new drugs are frequently administered to patients who have been excluded in the clinical trials. However, health professionals seldom recognize this. Focusing on monoclonal antibody drugs, we conducted a questionnaire survey of pharmaceutical companies and accumulated cases in which risk management differed between clinical trials and post-marketing.

Methods: We obtained information on exclusion criteria for clinical trials of monoclonal antibody preparations from pharmaceutical companies. We compared these exclusion criteria with the contraindicated items in the package insert.

Results: The most common exclusion criteria were “reproductive-related events”, “cancer-related events”, “HBV/HCV infection”,and “history of allergy/hypersensitivity”. The most common contraindications in the package insert were “history of allergy/hypersensitivity”, “other infectious diseases”, and “tuberculosis infection”. The average number of exclusion criteria for safety measures at the time of clinical trial was 10.1per drug, while that of contraindications was 2.1per drug; the difference was statistically significant. In addition, there were significant differences in one clinical trial exclusion criterion ( “upper age limit” ) and two contraindications ( “tuberculosis infection” and “other infectious diseases” ) between antineoplastic agents compared to therapeutic agents for autoimmune-related diseases. In half the products, serious adverse drug reactions related to the exclusion criteria that were not contraindicated were reported after marketing.

Conclusion: Because the contraindications at the time of marketing are drastically fewer compared to the exclusion criteria at the time of clinical trials, pharmacists should inform doctors of it and carefully monitor the outcomes of new drugs that have not been used with patients with complications.