Cladribine therapy in Myasthenia

Prior treatment

• Negative results (below the cut-off threshold) of determinations of acetylcholine receptor auto-aggressive antibodies (anti-AChR-ab) or muscle tyrosine kinase (anti-MUSK-ab).

Other illness

• Electrophysiological exponents of presynaptic disorders of neuromuscular conduction (facilitation phenomenon in electromyographic myasthenia gravis test).
• Coexistence of diseases that make it impossible to assess the disease state in the context of the severity of myasthenia gravis (e.g. cardiovascular or respiratory diseases clinically manifested by fatigue).
• Coexistence of diseases that reduce resistance to opportunistic infection, which may be the cause of complications of immunoactive treatment of myasthenia gravis (e.g. HIV, hepatitis B or C, tuberculosis) or recurrent herpes zoster in treatment.
• Tumour disease active at the time of the qualifying visit (W0) for the study, or completed non-deferred temporal (< 6 months) oncological treatment.

Lab values

• Significant deviation in basic research: - peripheral blood count: leukopenia < 1.5 x 109/l; - neck functions: creatinine > 1.4 mg/dl in women and > 1.5 mg/dl in men; - liver function: AST or ALT > 3x ggn; - anti-IgA infection in people with IgA deficiency (in case emergency treatment is needed due to intravenous administration of human immunoglobulins *IVIG). If there is improvement in follow-up, deviations from the above criteria are acceptable based on the patient's clinical presentation (to be at the decision of the Investigator).

Age

• Hypersensitivity to cladribine or to any of them has been helpful: - mechanical obstruction of the urinary tract (with attention to AChEI); - pregnancy (patients of childbearing age will be required to declare use of an effective method of contraception [Pearl index ≤2 ] from the qualifying visit (W0) during the trial and 6 months after its completion); - breastfeeding.
• No use of an effective method of contraception [Pearl index ≤ 2] by patients of childbearing age at the time of eligibility (visit W0) for the study until 6 months after the last dose of study medicinal product.

Other

• Unusual distribution of muscle weakness or lack of apocamnosis effect with other diagnosis (such as LEMS, OPMD).
• No use of barrier contraception by patients at the time of study eligibility (W0 visit) until 6 months after the last dose of study medicinal product.
• Other contraindications which, in the opinion of the Investigator, exclude the patient from participating in the study.

• Age > 18 years (no border).
• DETAILED CRITERIA - the main cohort: validity of second-line immunoactive treatment indicated by failure to achieve pharmacological remission according to MGFA post-interventional status despite symptomatic acetylcholinesterase inhibitor treatment at optimal doses combined with chronic oral steroid therapy with achievement of stable 4 weeks prior to the randomisation visit (W1D1) prednisone equivalent dose.
• DETAILED CRITERIA - complementary cohort: no immunoactive treatment (acceptable symptomatic treatment with acetylcholinesterase inhibitors) and nonacceptance of the patient's side for the sick steroid therapy dictated by the disease before side effects.
• Obtaining informed consent for the patient's participation in the entry.
• The characteristic clinical picture of myasthenia gravis with nonpainful movement of typical striated muscle groups with the intensity of professional development changing throughout the day.
• Increased cut-off titer of anti-acetylcholine receptor (anti-AchR-ab) or muscle tyrosine kinase (anti-MUSK-ab) involved in the pathogenesis of myasthenia gravis (historical result: untimed).
• The known status of thymus pathology based on the chest radiological examination (CT) (historical up to 5 years prior to qualifying visit or performed at qualifying visit) and / or the hist-path results of the removed thymus if the patient underwent a thymectomy.
• Corticosteroid dose stabilised ≥ 4 weeks prior to randomisation and a minimum 4-week withdrawal period from other immunosuppressive agents (cytostatic or biological) in the absence of lymphopenia and drug-induced parenchymal organ damage (liver, kidney).
• AChEI dose stabilised ≥ 4 weeks prior to randomisation (W1D1).
• Electrophysiological test result of the myasthenia test (historical up to 5 years before the qualifying visit) or the test can be performed at the qualifying visit (W0).
• MRI result of head with contrast (archived up to 5 years prior to qualifying visit or performed at qualifying visit).