¹Department of Clinical Pharmacology, School of Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany
²Institute of General Practice and Family Medicine, University Hospital, LMU Munich, Munich, Germany
³Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
⁴Rheumatology, Ruhr-Universität Bochum and Rheumazentrum Ruhrgebiet, Bochum, Germany
⁵Center for Clinical Trials and Department of Clinical Pharmacology, School of Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany

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Background: In recent years, several advanced disease-modifying drugs (DMDs) have been approved for the treatment of rare autoimmune disorders. However, data on the safety and effectiveness of these novel DMDs outside the pivotal trials is limited. Hence, the CONTRIBUTE project aims to assess the effectiveness and safety of selected DMDs for rare rheumatic and neurological diseases in routine clinical practice. As part of the project, we analyzed spontaneous reports documented in the EudraVigilance database for selected DMDs and selected conditions (Giant cell arteritis (GCA) and Primary progressive multiple sclerosis (PPMS)).

Materials and Methods: We conducted a retrospective analysis of spontaneous reports from the authorization year (RoActemra^©: 2009, Ocrevus^©: 2018) to 2024. The database records reactions according to the MedDRA (Medical Dictionary for Regulatory Activities) terminology at the preferred term (PT-Term) level. Patients who received RoActrema^© for treating GCA or Ocrevus^© for treating PPMS were included in the analysis. All descriptive analyses were conducted stratified for the two DMDs using Python (Version 3.12.4) and Excel (Version 2506).

Results: For the DMD RoActemra^© (Tocilizumab) n=1318 reactions including adverse drug reactions (ADRs) (n=319 (24.2%) serious ADRs) were identified. The five most reported PT-Terms were ‘off label use’ (n=53, 4.0%), ‘headache’ (n=28, 2.1%), ‘intentional product use issue’ (n=23, 1.7%), ‘neutropenia’ (n=20, 1.5%), and ‘diverticulitis’ (n =18, 1.3%). The three most frequent System Organ Classes (SOC) terms were ‘General disorders and administration site conditions’ (n=185, 14.0%), ‘Injury, poisoning and procedural complications’ (n=146, 11.0%), and ‘Gastrointestinal disorders’ (n=135, 10.2%).

For female patients 982 PT-Terms (74.5%) were reported. Patients over 65 years of age accounted for most reactions (n=634, 48.1%) whereas in n=566 (42.9%) reactions the age group was not specified.

The administration of Ocrevus^© (Ocrelizumab) for the treatment of PPMS led to n=2455 reactions including ADRs (n=553 (22.5%) serious ADRs). The five most frequent PT-Terms were ‘multiple sclerosis’ (n=72, 2.9%), ‘fatigue’ (n=57, 2.3%), ‘gait disturbance’ (n=53, 2.1%), ‘urinary tract infection’ (n=48, 1.9%), and ‘COVID-19’ (n=42, 1.7%). Regarding SOC-Terms the three most common categories were ‘General disorders and administration site conditions’ (n=453, 18.4%), ’Nervous system disorders’ (n=299, 12.1%), and ’Infections and infestations’ (n=242, 9.8%).

The sex distribution presented itself more evenly distributed with n=1305 (53.1%) female patients. Most reported reactions were for patients between age 18-64 (n=1270, 51.7%). 37.7% (n=927) of all reactions were not specified regarding age of the patient.

Conclusion: Our findings highlight the multitude of spontaneous reports for newly approved DMDs used in two rare diseases providing a deep insight into the safety profile of these drugs after approval. Within the project, we will further compare the safety of selected DMDs using data from clinical trials and secondary data to provide a comprehensive picture of potential side effects in a real-world healthcare setting.

Funding: The CONTRIBUTE project is funded by the German Federal Joint Committee (G-BA) (funding code: 01VSF23041).