Therapeutic efficacy and immunoregulatory effect of Qiangji Jianli Capsule for patients with myasthenia gravis

Abstract

Introduction: Myasthenia gravis (MG) is an autoimmune disease in which antibodies directly target components of the neuromuscular junction, causing neuromuscular conduction damage that leads to muscle weakness. The current pharmaceutical treatment for MG is still not ideal to address the problems of disease progression, high recurrence rate, and drug side effects. Clinical observations suggest that traditional Chinese medicine (TCM) can strengthen immunity and improve symptoms of MG patients, delay the progression of the disease, reduce or even prevent the need for immunosuppressive therapy when used in combination with acetylcholinesterase inhibitors or low-dose prednisone, as well as improve the quality of life of patients. The Qiangji Jianli Capsule (QJC) is a combination of medicinal herbs which is used in traditional Chinese medicine. Since MG is a rare disorder, randomized controlled trials comparing large cohorts are difficult to conduct. Therefore, we proposed to aggregate data from a small series of N-of-1 trials to assess the effect of the Chinese medical prescription QJC, which strengthens the spleen and nourishes Qi, as an add-on treatment for MG with spleen and stomach Qi deficiency syndrome. Methods and analysis: Single-center, randomized, double-blind, multiple crossover N-of-1 studies will compare QJC versus placebo in 5 adult MG patients with spleen and stomach Qi deficiency syndrome. Patients will undergo 3 cycles of two 4-week intervention periods. According to the treatment schedule, patients will continue to be treated with pyridine bromide tablets, prednisone acetate, tablets and/or tacrolimus capsules throughout the entire trial. Each period consisting of 4-week oral add-on treatment with QJC will be compared with 4-week add-on treatment with a placebo. The primary endpoints are quantitative myasthenia gravis (QMG) test; measurement of the amount of T reg cells and cytokines such as interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), and transforming growth factor-β (TGF-β); and corticosteroid or immunosuppressive agent dosage. Secondary outcome measures: Clinical: Evaluation of the effect of TCM syndromes; MG-activities of daily living (MG-ADL) scales; adverse events. Ethics and dissemination: This study was approved by The First Affiliated Hospital of Guangzhou University of Chinese Medicine (GZUCM), No. ZYYECK[2019]038. The results will be published in a peer-reviewed publication. Regulatory stakeholders will comment on the suitability of the trial for market authorization and reimbursement purposes. Trial registration: Chinese Clinical Trial Register, ID: ChiCTR2000033516. Registered on 3 June 2020, http://www.chictr.org.cn/showprojen.aspx?proj=54618 .

Development of a Computerized Adaptive Test for Quantifying Chinese Medicine Syndrome of Myasthenia Gravis on Basis of Multidimensional Item Response Theory

“…Spleen-kidney deficiency syndrome was reported to be the major syndrome of MG patients in China. [16,34]. In TCM theory, the kidney governs the bone and acts as the root of primordial Qi to dominate growth and development.…”

Effectiveness of modified Buzhong Yiqi decoction in treating myasthenia gravis: study protocol for a series of N-of-1 trials

“…Because of the heterogeneous components of Chinese herbs, the onset time and half-time of Chinese herbs are hard to confirm [ 24 ]. According to previous clinical observation and preliminary trial [ 11 ], we decided to set the intervention period or control period for 4 weeks and the wash-out interval for 1 week. Each cycle comprises a 4-week intervention period with MBYD combining conventional western medicine and a 4-week control period with placebo with the same western medicine in random order.…”

“…A study found that using TCM combined with western medicine might improve the total effect and reduce the risk of MG relapse [ 9 ]. According to the TCM characteristic theory of “spleen governing muscle,” MG is generally diagnosed as “spleen qi deficiency syndrome” and thereby, strengthening the spleen and replenishing qi is a common therapeutic strategy of MG in TCM, which has played a positive role in clinical practice of MG [ 10 , 11 ]. Buzhong Yiqi decoction (BYD), a classical qi -supplementing formula in TCM, is the most frequently used prescription to treat MG. A study showed that BYD modulated the balance of Treg and Th17 cells in patients with MG and downregulated the serum AChR antibody level [ 12 ].…”

Effectiveness of Modified Buzhong Yiqi Decoction In Treating Myasthenia Gravis: Study Protocol For A Series Of N-of-1 Trials

“…Because of the heterogeneous components of Chinese herbs, the onset time and half-time of Chinese herbs are hard to con rm (24). According to previous clinical observation and preliminary trial (11), we decided to set the intervention period or control period for 4 weeks and the wash-out interval for 1 week. Each cycle comprises a 4-week intervention period with MBYD combining conventional western medicine and a 4-week control period with placebo with the same western medicine in random order.…”

“…A study found that using TCM combined with western medicine might improve the total effect and reduce the risk of MG relapse (9) . According to the TCM characteristic theory of "spleen governing muscle", MG is generally diagnosed as "spleen qi de ciency syndrome" and thereby, strengthening spleen and replenishing qi is a common therapeutic strategy of MG in TCM, which has played a positive role in clinical practice of MG. (10,11) Buzhong Yiqi Decoction (BYD), a classical qi-supplementing formula in TCM, is the most frequently used prescription to treat MG. A study showed that BYD modulated the balance of Treg and Th17 cells in patients with MG, downregulated the serum AChR antibody level (12). Modi ed BYD (MBYD) is based on BYD and adds other Chinese herbs to treat MG patients' speci c or concurrent symptoms synergistically.…”