Efficacy and Safety of Tacrolimus Therapy for a Single Chinese Cohort With Very-Late-Onset Myasthenia Gravis

Abstract

Background and PurposePrevious studies have found tacrolimus to be a favorable drug for treating different types of myasthenia gravis (MG), but few have focused on very-late-onset MG (VLOMG). This study evaluated the efficacy and safety of tacrolimus for VLOMG therapy.MethodsThis was a retrospective single-center cohort study of 70 patients with VLOMG (onset ≥65 years) who visited Peking University First Hospital in 2019. Participants were divided into the tacrolimus (Tac) group and the control group based on tacrolimus usage. We further divided the Tac group into patients treated without corticosteroids and with corticosteroids. Sociodemographic features, clinical profiles, and outcomes were compared between different therapies and further analyzed by multivariate regression. Details of tacrolimus treatment, comorbidities, and adverse drug reactions (ADRs) were described.ResultsAmong 70 patients, the median (interquartile range) age at onset was 71 (68–77) years, and the follow-up duration was 27 (27-29) months. Most patients were types I (28%) and III (40%) according to the MG Foundation of America (MGFA) classification. In the Tac group, tacrolimus treatment was maintained for 36 (27-38) months. The dosage at the final evaluation was 1.0 (1.0–1.75) mg/day, and the last blood concentration test was 4.25 (2.85–5.7) ng/ml. A total of 43% reached remission, and 37% improved based on MGFA postintervention status (MGFA-PIS). For the 9 patients, newly diagnosed at enrollment within this group, MG activities of daily living (MG-ADL) decreased significantly from 3 (2-5) to 2 (1-2) (p = 0.041). Regarding the 13 patients, coadministering Wuzhi capsules the tacrolimus concentration increased from 2.75 (1.4–3.8) ng/ml to 5.95 (5.1–7.0) ng/ml (p = 0.012). No significant differences in outcomes were observed between tacrolimus treatment without and with corticosteroids or between the Tac group and the control group. A total of 93% had at least one comorbidity. ADRs related to tacrolimus emerged in 25% (9/36) of patients, most of which were not serious and reversible.ConclusionsTacrolimus is effective and safe in treating VLOMG. Tacrolimus monotherapy without corticosteroids can be used as an initial and maintenance treatment for VLOMG. Wuzhi capsules work well in elevating tacrolimus concentrations in this population.

A Pilot Study on Tocilizumab in Very-Late-Onset Myasthenia Gravis

“… 5–7 To date, the results of a variety of retrospective studies have supported the clinical benefit of immunotherapy (eg, glucocorticoid, azathioprine, and tacrolimus) in treating patients with VLOMG. 5 , 8 , 9 …”

“…[5][6][7] To date, the results of a variety of retrospective studies have supported the clinical benefit of immunotherapy (eg, glucocorticoid, azathioprine, and tacrolimus) in treating patients with VLOMG. 5,8,9 The pro-inflammatory cytokine, interleukin (IL)-6, is an important mediator of the inflammatory process in MG and may contribute to the pathogenesis of VLOMG. IL-6 has a variety of biological properties, such as the stimulation of B cell differentiation, antibody production, activation of T cells, and induction of naïve T cells to differentiate into T helper type 17 (Th17) and follicular T cells.…”