Most MG Patients, Especially Men and Patients With Late-onset Disease, Respond to Plasma Exchange

A vast majority of patients with myasthenia gravis (MG) responded to treatment with plasma exchange and half experienced symptom relief, according to a study.

The findings also showed that men and patients with late-onset MG were more likely to have successful response to the treatment.

The study, “Excellent response to therapeutic plasma exchange in myasthenia gravis patients irrespective of antibody status,” was published in the Journal of Clinical Apheresis.

Plasma exchange, or plasmapheresis, is a first-line treatment for acute crisis and prior to thymectomy (thymus removal) in MG patients. The procedure, which removes circulating autoantibodies responsible for dysfunction at the neuromuscular junction — the site where nerve cells and muscles communicate — has led to both lower levels of anti-acetylcholine receptor (AChR) antibodies and increased strength in people with MG. Also, similar to intravenous immunoglobulin (IVIG), plasma exchange may have an immunomodulatory effect, lessening the activation of lymphocytes (white blood cells).

Given the scarcity of studies about which patients with MG will experience symptom resolution with plasma exchange, and which ones will require chronic maintenance therapy, a team at University of Texas Southwestern Medical Center reviewed data of 58 patients to clarify the clinical characteristics and blood markers associated with response to this treatment.

Specifically, investigators studied whether response to plasma exchange correlated with factors such as antibody status, MG type, age at MG onset, gender, having a thymoma (a tumor in the thymus), or undergoing a thymectomy.

All patients (29 men and 29 women, age range 18–86, mean age 54.8 years) were treated with 1.0 volume plasma exchange between January 2015 and April 2017. During treatment, 49 patients also were receiving Mestinon (pyridostigmine), 30 patients prednisone, 26 patients CellCept (mycophenolate mofetil, by Genentech), nine patients Prograf (tacrolimus, by Astellas), and three were receiving azathioprine. Also, 19 patients received IVIG and rituximab, 12 while on plasma exchange.

The patients’ mean age at MG symptoms onset was 48.2 years, range 17–83. The most common symptoms were bulbar muscles weakness (88%) and ptosis (drooping eyelid, 66%). Plasma exchange duration ranged from four days to more than 10 years.

Fifty-one patients (88%) were antibody-positive; 44 for targeting AchR and seven targeting muscle specific kinase (MuSK). Twenty-one patients underwent thymectomy and eight patients had a thymoma, three malignant.

After excluding the six patients who underwent only short course plasma exchange (three or five procedures) before thymectomy, investigators found that 26 of 52 patients (50%) had symptom resolution, 72% of whom were being treated for acute MG exacerbation only. All patients with complete response to treatment — complete resolution or sufficient improvement to not require further plasma exchange — had clinical improvements, as assessed with the Myasthenia Gravis Foundation of America (MGFA) system. One of these patients achieved complete stable remission and four showed minimal manifestations.

Twenty-four patients required maintenance plasma exchange (19 were antibody-positive), most experiencing improvements in the MGFA assessment. Only two patients, both AChR antibody-positive, had little to no response to plasma exchange, one of whom stopped treatment after nearly two years due to intolerance, and the other later diagnosed with HSV encephalitis and diffuse large B-cell lymphoma.

When analyzing the 45 patients with MG-associated antibodies, the results revealed that 24 (53%) had resolution of symptoms — 22 of 38 (58%) of AchR-positive patients and two of 7 (29%) of MuSK-positive patients — 19 (42%) required maintenance treatment, and two (4%) had little to no response, both with anti-AChR antibodies.

The seven patients without MG antibodies (seronegative) showed similar response to MuSK-positive patients, as five required maintenance treatment at nine- to 21-day intervals, and only two experienced resolution of symptoms following acute course therapy.

Among the patients with both pre- and post-plasma exchange antibody levels available, six of 15 (40%) with anti-AChR antibodies had complete response, including three on acute treatment. Five showed lower antibody levels, but one had higher amounts. Seven patients (47%) required maintenance plasma exchange, six of whom experienced a decrease in antibody levels.

Two AChR-positive patients had no treatment response and unchanged antibody level. As for the only MuSK–positive patient in this group, the antibody amount declined, but maintenance therapy was required.

Three of nine patients with early-onset MG (before age 50) and AChR antibodies showed complete response. Six of these patients needed maintenance treatment. In turn, 15 of 22 patients (68%) with late-onset MG (at or after age 50) and anti-AChR antibodies experienced complete response. Six required maintenance treatment, and one did not respond to plasma exchange.

Nineteen of 28 men (68%) experienced symptom resolution. Maintenance treatment was required by eight, while one did not respond. In turn, women showed a lower rate of complete response, as only seven of 24 (29%) had resolution of symptoms. Sixteen required maintenance treatment and one had no response.

Gender significantly correlated with response to plasma exchange, with men more likely to experience complete response and women more likely to require maintenance treatment.

Four of eight patients with thymoma showed resolution of symptoms, three of whom received plasma exchange for MG crisis only. Three required maintenance therapy, and one did not respond. The data further showed that seven of 15 patients who underwent thymectomy had resolution of symptoms, including three with acute treatment. Six needed maintenance therapy and two did not respond to plasma exchange.

Neither thymoma nor thymectomy were significantly associated with response to plasma exchange.

“In conclusion, our study showed 96% response rate to [plasma exchange] in MG; however, only patient gender and late onset MG were significantly associated with treatment response,” the scientists wrote.