Cladribine, a medication for relapsing multiple sclerosis, eased symptoms and reduced the need for high-dosage corticosteroids in people with treatment-resistant myasthenia gravis, a small study shows.
The study, titled “Cladribine in myasthenia gravis: a pilot open‐label study,” was published in the European Journal of Neurology.
Current strategies for myasthenia gravis treatment include symptomatic relief, such as cholinesterase inhibitor Mestinon (pyridostigmine), chronic immunosuppressive therapies that target the underlying immune dysregulation, rapid but short-acting immunomodulating treatments, and surgery.
New therapies involving monoclonal antibodies — laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, or mimic the immune system’s attack on abnormal/diseased cells — have been shown to be effective in difficult-to-treat patients. However, these treatments can eventually become intolerable and produce significant side effects. Moreover, strong evidence is lacking about their long-term efficacy.
An oral medication called cladribine, which is sold under the name Mavenclad and approved for relapsing remitting multiple sclerosis, works by selectively killing lymphocytes, a specific type of white blood cell, including B- and T-cells.
Such cells produce autoantibodies that damage cells and tissues in patients with myasthenia gravis, compromising the communication between nerve cells and muscles. Importantly, cladribine acts fast and almost without any effects on any other type of cell.
Investigators at the Medical University of Lublin in Poland decided to assess cladribine’s effectiveness in people with difficult-to-treat (refractory) myasthenia gravis.
Thirteen patients (five women and eight men; mean age of 55 years at disease onset, age range of 32 to 81) received cladribine. Among these patients, seven were unresponsive to maximal doses of steroids and/or immunosuppressants, and six were intolerant to treatment.
Cladribine was administered subcutaneously (under the skin) at a dose of 0.30 mg/kg of body weight in divided doses, over two consecutive days. Treatment administration was driven by clinical response.
“The dose was repeated on monthly intervals, if it failed to exert significant clinical improvement based on regular assessments,” the authors said.
Results revealed that 11 patients had their disease-related signs and symptoms, as measured by the Myasthenia Gravis Composite (MGC) scale, significantly eased during therapy.
The significant clinical improvement persisted six months after the first dose. The mean MGC score at enrollment in the study, 15.1 points, significantly decreased to 6.3 points at six months (significant clinical improvements were considered to be a reduction of the MGC score by at least 3 points). Two patients did not achieve any significant improvement in the MGC score.
In addition, the dose of prednisolone (a corticosteroid that’s commonly used in myasthenia gravis to reduce immune system activity) decreased from 9.5 mg at the beginning of the study to 1.9 mg. Cladribine did not cause any serious side effects, and none of the study subjects required immune therapies, such as intravenous immunoglobulin and plasma exchange.
“In conclusion, cladribine seems to be a promising drug for difficult treatments to [myasthenia gravis] patients,” the scientists said. “Further studies are needed to establish optimal dosing regime and to assess long-term efficacy and a safety profile.”