The burden of disease in seronegative Myasthenia Gravis: A patient-centered perspective

Sophie Lehnerer ^* Regina Stegherr Ulrike Grittner Maike Stein Lea Gerischer Frauke Stascheit Meret Herdick Paolo Doksani Andreas Meisel Sarah Hoffmann

• Charité University Medicine Berlin, Berlin, Germany

Objective: Myasthenia gravis (MG) is an autoimmune disorder primarily caused by autoantibodies against the acetylcholine receptor (AChR). Approximately 15% of MG patients, categorized as seronegative (snMG), lack detectable antibodies. Due to snMG status, there may be a diagnostic delay. Moreover, there is limited data on treatment response in comparison to AChR-Ab+ patients. This study examines the burden of disease, treatment response, and quality of life in snMG patients in comparison to AChR-ab+ MG patients and healthy controls.Methods: Questionnaire-based survey collecting sociodemographic and clinical data including antibody status, therapy, treatment response and self-rated disease severity along with standardized assessments such as MG-ADL (activities of daily living) and the Short Form Health (SF-36, generic Health-Related Quality of Life, HRQoL). HRQoL was evaluated through matched-pairs analyses. Participants from a general health survey served as control group. Negative binomial regression was applied to evaluate the impact of antibody status on MG-ADL.Results: Compared to AChR-ab+ patients, snMG patients (n=237) were younger at symptom onset (median age 42 [IQR 30.5/53] vs. 51 [31/64] years, p<0.001) and had longer diagnostic delays. Complete stable remission was less frequent in snMG patients (15.9% vs. 27.8%, p<0.001), and they reported higher disease severity (52.8% medium, 9.5% severe vs. 41.9% medium, 8.5% severe, p=0.005). snMG patients had higher MG-ADL scores (median 5 [IQR 2/9] vs. 3 [1/6], p<0.001) and more employment restrictions (64.4% vs. 49.3%, p<0.001). Furthermore, compared to healthy controls snMG patients showed worse outcomes in all domains of the SF-36.Burden of disease in snMG patients is higher compared to AChR-ab+ MG due to delay in diagnosis, worse treatment response as well as sociodemographic factors. These findings highlight the challenges patients and treating physicians face in snMG. There is a high need for earlier diagnosis, improved diagnostic tools as well as inclusion of snMG patients in clinical trials to address their unique therapeutic challenges.Trial Registration: clinicaltrials.gov NCT03979521. Registered 7 June 2019 (retrospectively registered)