Post-authorization changes in the safety and efficacy assessment, recommended indications, and drug quality profile of adalimumab: a chronological overview.

Abstract

The intention of the present study was to demonstrate the postauthorization changes of adalimumab (European trade name: Humira), evaluating the variations in its safety, efficacy, and quality profile. Type-II, major variations of the Summary of Product Characteristics (SmPC) from September 8, 2003 to November 19, 2015, were analyzed, which, according to Commission Regulation (EC) No. 1234/2008, have to reflect changes that may have a significant impact on the safety, efficacy, or quality profile of a medicinal product. A unique scoring system was developed to estimate the influence of post-authorization variations in the safety and efficacy assessment, recommended indications, and drug-quality profile of adalimumab. In the past 13 years, adalimumab has been proven to be beneficial in 12 indications. In this time period, the safety-related subsections of the SmPC expanded the most. 27.12% of the total changes were found in subsection 4.8 (Undesirable effects), 19.77% in subsection 4.4 (Special warnings and precautions for use). Section 5 (Pharmacological properties) was also significantly modified (19.77%) thanks to the numerous clinical trials studying the effects of adalimumab. Concerning the total changes in the content of the SmPC, 58.4% was safety, 29.4% efficacy, and only 1.8% was quality-related alteration. The rest, 10.4%, was considered as administrational modification. The extensive postauthorization research (both surveillance and clinical trials) significantly have increased our knowledge about the efficient and safe use of the medicine and have made adalimumab one of the top-10 selling pharmaceuticals worldwide. Regarding ongoing clinical trials, more pediatric indications are expected.