Tacrolimus as Single-Agent Immunotherapy and Minimal Manifestation Status in Nonthymoma Myasthenia Gravis

Duan, Weiwei; Peng, Yuyao; Wu, Jin; Ouyang, Shan; Yang, Huan

doi:10.1155/2021/9138548

Cited by 6 publications

(8 citation statements)

References 29 publications

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“…Outcome measurements indicated tacrolimus non-inferior to other medications, consistent with one study on MG of Osserman grades III and IV ( 16 ). Although the positive effects here seemed weaker than several earlier studies that reported remission rates ≥ 64% ( 11 , 12 , 15 , 16 , 21 ), the differences could be explained by the already achieved improvement before baseline and relatively stable MG status at enrollment. Almost all the previous studies started with tacrolimus initiation, while the majority of our patients began with a notable duration of treatment; conceivably, there was less space for a positive effect to be displayed.…”

Section: Discussioncontrasting

confidence: 97%

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

et al. 2022

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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.

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Section: Discussioncontrasting

confidence: 97%

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

et al. 2022

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“…However, the application of these regimens could be limited due to their slow onset of action and adverse events 2,13 . Previous studies suggest treatment of tacrolimus in MG may circumvent these limitations 6–8,16 . Mono‐tacrolimus has been applied in membranous nephropathy, refractory ulcerative colitis and heart transplantation 17–21 .…”

Section: Discussionmentioning

confidence: 99%

“… 2 , 13 Previous studies suggest treatment of tacrolimus in MG may circumvent these limitations. 6 , 7 , 8 , 16 Mono‐tacrolimus has been applied in membranous nephropathy, refractory ulcerative colitis and heart transplantation. 17 , 18 , 19 , 20 , 21 Our results demonstrated that mono‐tacrolimus therapy has fast action onset with minimum adverse events in MG. Tacrolimus exerts its effect by inhibiting the calcineurin activity and downregulating the transcription of inflammatory cytokines, which results in the suppression of T‐cells activity and antibody production in B cells.…”

Section: Discussionmentioning

confidence: 99%

“… 5 It has also been used as monotherapy for induced remission of various symptoms with fast onset in MG patients. 6 , 7 More recently, a retrospective, noncontrolled study showed the favorable effects of mono‐tacrolimus initial immunotherapy on MG. 8 However, no study has compared the effectiveness and safety between mono‐tacrolimus and mono‐glucocorticoids regimens in MG.…”

Section: Introductionmentioning

confidence: 99%

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Comparison between mono‐tacrolimus and mono‐glucocorticoid in the treatment of myasthenia gravis

Fan

Lei

et al. 2023

Ann Clin Transl Neurol

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Objective: Use of tacrolimus in mild to moderate myasthenia gravis (MG) is generally limited to glucocorticoid-refractory cases; the advantage of monotacrolimus over mono-glucocorticoids is unknown. Methods: We included mild to moderate MG patients treated with mono-tacrolimus (mono-TAC) or mono-glucocorticoids (mono-GC). The correlation between the immunotherapy options and the treatment efficacy and side effects were examined in 1:1 propensity-score matching. The main outcome was time to minimal manifestations status or better (MMS or better). Secondary outcomes include time to relapse, the mean changes in Myasthenia Gravis-specific Activities of Daily Living (MG-ADL) scores and the rate of adverse events. Results: Baseline characteristics showed no difference between matched groups (49 matched pairs). There were no differences in median time to MMS or better between the mono-TAC group and mono-GC group (5.1 vs. 2.8 months: unadjusted hazard ratio [HR], 0.73; 95% CI, 0.46-1.16; p = 0.180), as well as in median time to relapse (data unavailable for the mono-TAC group since 44 of 49 [89.8%] participants remained in MMS or better; 39.7 months in mono-GC group: unadjusted HR, 0.67; 95% CI, 0.23-1.97; p = 0.464). Changes in MG-ADL scores between the two groups were similar (mean differences, 0.3; 95% CI, À0.4 to 1.0; p = 0.462). The rate of adverse events was lower in the mono-TAC group compared to the mono-GC group (24.5% vs. 55.1%, p = 0.002). Interpretation: Mono-tacrolimus performs superior tolerability with non-inferior efficacy compared to mono-glucocorticoids in mild to moderate myasthenia gravis patients who refuse or have a contraindication to glucocorticoids.

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“…Timektomija se sprovodila kod svih pacijenata sa timomom, kao i kod pacijenata mlađih od 50 godina sa generalizovanom formom AChR-pozitivne SAMG. Studija koja je ispitivala efikasnost timektomije (MGTX) je nedvosmisleno potvrdila da je ona efikasna kod pacijenata sa AChR MG mlađih od 65 godina i da u ovoj grupi ona rezultira boljim terapijskim ishodom, potrebom za manjim dozama steroida i ređom potrebom za dodatnim imunosupresivnim lekom 41 . Timektomiju je važno uraditi što ranije, a najbolje u prvih 6 meseci do dve godine nakon početka SAMG, jer je pokazano da u ovim slučajevima ona ima posebno povoljan efekat [20][21][22] .…”

Section: Terapija Samgunclassified

Treatment of acquired autoimmune myasthenia gravis: Where are we today?

Lavrnić¹

2022

Galenika Med J

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Acquired autoimmune myasthenia gravis (MG) is a prototype of autoimmune disease in which autoantibodies directed against various antigens of the neuromuscular junction, leading to impaired neuromuscular transmission with clinical presentation of fluctuating weakness and excessive fatigue of transverse striated skeletal muscles. In 85% of patients with MG there are antibodies to the nicotine acetylcholine receptor of the postsynaptic muscle membrane (nAChR), in 5-8% of patients there are antibodies to muscle-specific tyrosine kinase (MuSK), in 1-2% of antibodies to low-density lipoprotein receptor-related protein 4 (LRP4), while in the remaining 10% none of the mentioned autoantibodies can be detected, and these patients are classified in the group of so-called "seronegative" MG. It is well known that this antigenic specificity affects both the clinical presentation and the therapeutic response, course and prognosis of the disease, which is why the early serological confirmation of the diagnosis is important. In this way, determining the exact profile of autoantibodies can provide a significantly more efficient, personalized therapeutic approach for each patient, and thus improve the prognosis and quality of life of these patients. In general, when a patient is diagnosed with MG, the goal is to alleviate the symptoms of the disease as soon as possible, as well as to induce remission or minimal manifestations of the disease in the following period. MG therapy can be roughly divided into symptomatic therapy, which includes drugs that alleviate the symptoms of weakness and fatigue, causal therapy, which immunomodulates the pathogenetic process that affects the course of MG and temporary therapeutic procedures to achieve rapid improvement in patients to avoid or treatment of the most severe clinical manifestations, the so-called "crisis" of MG. Symptomatic MG therapy involves the use of acetylcholinesterase inhibitors, represented by pyridostigmine bromide. It works by relieving the symptoms of MG in a short period of time, 4-8 hours. Causal therapy acts on the pathogenetic process on the basis of MG and it includes corticosteroids as first-line drugs and immunosuppressive drugs: azathioprine, cyclosporine A, mycophenolate mofetil, etc, while temporary therapeutic procedures include therapeutic plasma changes and intravenous immunoglobulins. All the above mentioned MG therapies are is effective in most patients with this disease, but it should be emphasized that, on the one hand, to achieve its full effect usually takes several months, and on the other hand, that such prolonged therapy is often followed by the occurrence of various side effects that require its reduction or complete cessation. With advances in immunology, molecular biology, and rapid drug development, new agents are being developed today that have much more selective immune targets, save the rest of the immune system, have lower toxicity, and a much faster onset of action MG. Some of these drugs are already being used successfully today, but we can freely say that the door to highly selective immunotherapy in MG has just been opened and that this is certainly the therapy of the future.

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Tacrolimus as Single-Agent Immunotherapy and Minimal Manifestation Status in Nonthymoma Myasthenia Gravis

Cited by 6 publications

References 29 publications

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

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

Comparison between mono‐tacrolimus and mono‐glucocorticoid in the treatment of myasthenia gravis

Treatment of acquired autoimmune myasthenia gravis: Where are we today?

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