Comparing the Effectiveness of Different Vaccines in Individuals with and without Autoimmune Diseases: A Study Protocol for a Target Trial Emulation

Robin Denz^1*Heike van de Sand²Jale Basten¹Katharina Meiszl¹Marianne Tokic¹Theresa Oganowski³Thomas Grüter^3,4Stephanie Stock⁵Dusan Simic⁵Arim Shukri⁵Uta Kiltz^6,7Maria Zacharopoulou⁷Horst Christian Vollmar⁸Ina Carola Otte⁸Chantal Giehl^8,9Romy Lauer^1,8Anastasia Suslow⁸Andreas Stallmach¹⁰Anika Franz¹⁰Ursula Marschall¹¹Joachim Saam¹¹Catharina Schumacher¹¹Katja Blaschke²Ingo Meyer²Kerstin Hellwig³Nina Timmesfeld¹

• ¹Ruhr University Bochum, Department of Medical Informatics, Biometry and Epidemiology, Bochum, Germany
• ²University of Cologne, PMV Research Group, Medical Faculty and University Hospital Cologne, Cologne, Germany
• ³Ruhr University Bochum, Department of Neurology, St. Josef Hospital, Bochum, Germany
• ⁴Evangelical Hospital Lippstadt, Department of Neurology and Stroke Unit, Lippstadt, Germany
• ⁵University of Cologne, Institute of Health Economics and Clinical Epidemiology (IGKE), Faculty of Medicine and University Hospital Cologne, Cologne, Germany
• ⁶Rheumazentrum Ruhrgebiet, Herne, Germany
• ⁷Ruhr University Bochum, Department of Rheumatology, Bochum, Germany
• ⁸Ruhr University Bochum, Institute of General Practice and Family Medicine (AM RUB), Medical Faculty, Bochum, Germany
• ⁹Ruhr University Bochum, Department of Geriatric Medicine, Marien Hospital Herne, Herne, Germany
• ¹⁰Jena University Hospital, Department of Internal Medicine IV (Gastroenterology, Hepatology and Infectious Diseases), Jena, Germany
• ¹¹BARMER Institute for Health System Research, Department Medicine and Health Services Research, Wuppertal, Germany

Aim: This article presents the study protocol of a retrospective cohort study designed to compare the effectiveness of herpes zoster, and influenza vaccines in individuals with multiple 1 Denz et al. Vaccine Effectiveness in Individuals with Autoimmune Diseases sclerosis (MS), chronic inflammatory bowel diseases (IBD) or chronic inflammatory rheumatic diseases (CIRD) to individuals without these diseases, using claims data of one of the largest population based health insurances in Germany.Background: Individuals with autoimmune diseases such as MS, IBD and CIRD are more susceptible to vaccine preventable infectious diseases such as influenza and herpes zoster, due to the autoimmune disease itself, the presence of comorbidities and immunosuppressive therapies. Vaccines are the primary means to prevent such diseases. The efficacy of these vaccines is usually estimated using large randomized controlled trials, from which patients with MS, IBD and CIRD are often excluded. It is therefore unclear whether these vaccines are also effective for these patients.Design: A target trial emulation based on observational claims data of a statutory health insurance company is proposed.Methods: This study will aim to emulate multiple target trials to compare the effectiveness of herpes zoster and influenza vaccines in patients with and without MS, IBD and CIRD using data from a large German statutory health insurance provider (BARMER). The primary outcome for each vaccine effectiveness analysis is the disease itself. The analysis will be carried out using both time-dependent matching and a multivariable Cox proportional hazards model in conjunction with g-computation. Additionally, the moderating effect of immunosuppressive therapies on the vaccine effectiveness will be estimated using a stratified secondary analysis.Discussion: This study will estimate and compare the effectiveness of influenza and herpes zoster vaccines in individuals with and without MS, IBD and CIRD. Because of the large amount of data, this study will also be able to investigate the role of the immunosuppressive medication on vaccine effectiveness, which may provide guidance for vaccine administration guidelines.