Long-term Immunotherapy for MG Linked to Anemia in Female Patients

MG severity significantly worse in female patients with anemia, study finds

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Long-term immunotherapy may cause anemia in female patients with myasthenia gravis (MG), according to a Japanese study that found that women with this blood condition — one of the potential side effects of immunotherapy — had significantly worse disease severity.

Anemia, a condition marked by a low number of red blood cells circulating in the body, also was linked to a poorer quality of life among patients. According to researchers, monitoring of hemoglobin levels is important to guarantee the best care and management of female patients with MG.

“We think that female MG patients receiving intensive and long-term immunotherapy may be vulnerable to iron metabolism,” the team wrote, calling for further research into “whether correction for anemia improves [patients’ quality of life] scores.”

The study, “Anemia in female patients with myasthenia gravis,” was published in journal PLOS One.

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MG is an autoimmune disease caused by autoantibodies that wrongly attack the body’s own proteins involved in nerve-muscle communication, leading to muscle weakness in patients.

Investigating anemia in women with MG

Females are three times more likely to be diagnosed with early onset MG — when the disease arises in patients younger than age 50 — than males. Anemia also affects females more frequently.

Poor nutrition, lack of iron, deficient nutrient absorption, infections, and genetic diseases are the most common causes for anemia. Autoimmune diseases and certain medications also have been associated with anemia.

However, the prevalence of anemia among female patients with MG and its impact ion their quality of life are currently unknown.

To fill this knowledge gap, researchers in Japan analyzed data from 215 female MG patients who were followed at the Keio Hospital, in Tokyo, between January and December 2021.

After MG diagnosis, 40% of them (85 participants) experienced an episode of moderate or severe anemia. Anemia was considered moderate to severe when the levels of hemoglobin — the protein responsible for transporting oxygen in red blood cells — fell below 11 grams per deciliter (g/dL).

The team then compared these 85 patients — the anemia group — with the 130 female patients who did not have a history of anemia, who were dubbed the non-anemia group. No differences were found between the two groups in terms of age, MG duration, body mass index (a measure of body fat), smoking habits, and menopause.

MG severity was significantly worse in female patients with anemia compared with the non-anemia group, the researchers found. This was assessed by the Myasthenia Gravis Foundation of America (MGFA) clinical classification, which divides patients according to five main classes of increased severity.

The frequency of bulbar symptoms — those involving the face and neck — was greater in the anemia group (61% vs. 45%). Yet, no differences were found for myasthenic crises, which are episodes of MG worsening.

Quantitative MG scores, a measure of MG severity, also were greater in the anemia group than in the non-anemia group (mean 15.8 vs. 13.1).

The data showed that females with anemia more frequently used immunotherapies than those without the blood condition. Among the immunotherapies used were prednisolone, calcineurin inhibitors, plasma exchange, intravenous immunoglobulin, and anti-complement therapy.

Blood work showed that 49 female MG patients (23%) had iron-deficiency anemia. To find a possible cause, researchers investigated the prevalence of gynecological and gastrointestinal diseases arising after MG diagnosis.

The findings revealed that both gynecological (37% vs. 15%) and gastrointestinal disorders (21% vs. 5%) were more frequent among females with anemia than in those without it.

Meanwhile, a history of chronic infections, which also may underlie anemia, was found only in three patients (1%).

“Our analysis indicated that none of the diseases were responsible for the anemia observed in our patients,” the researchers wrote. The only exception was for one patient with a thymoma, a rare tumor in the thymus gland that is found in up to 15% of MG patients.

When considering the lifestyle information of the 85 MG patients with anemia, poverty, malnutrition, and diet were excluded as possible direct causes of anemia.

In sum, a direct cause for anemia remained unknown for 27 of the 85 (32%) female MG patients with anemia.

Because no differences were seen in hemoglobin levels between anemia patients with a known versus unknown cause, researchers reasoned that anemia was likely caused by the long-term use of immunotherapy, and was among its key side effects in these patients.

Treatment for any underlying disease, as well as iron supplements, were effective in 64 MG patients with anemia (75%), with the levels of hemoglobin rising above the anemia threshold (11 g/dL).

Finally, the team analyzed data on 215 females with MG with and without anemia to assess the condition’s impact on activities of daily living and quality of life.

A correlation was found between low hemoglobin levels and poorer quality of life, as measured by the revised scale of the 15-item Myasthenia Gravis Quality Of Life (MG-QOL) questionnaire.

Overall, these findings suggest that “long term immunosuppressive therapy can cause anemia in female MG patients,” with anemia having a negative impact on quality of life, the researchers wrote.

“Monitoring hemoglobin levels is necessary for best management of female MG patients,” they wrote.