Despite Side Effects, Pyridostigmine Perceived as Moderately Effective

Dutch study involved myasthenia gravis patients using the front-line treatment

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Pyridostigmine is perceived as being moderately effective at easing myasthenia gravis (MG) symptoms, but often is accompanied by side effects, a study of Dutch patients revealed.

Researchers noted the findings do not indicate a need for changes to current guidelines, which recommend the use of pyridostigmine as a first-line treatment for MG.

“Our results can be used to guide shared decision making, prior to starting symptomatic treatment for MG,” the researchers wrote.

The study, “The effectiveness and side effects of pyridostigmine in the treatment of myasthenia gravis; a cross-sectional study,” was published in the journal Neuromuscular Disorders

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MG Symptoms Weigh on Life Quality, Particularly for Women

Pyridostigmine (sold as Mestinon, among other brand names) is an oral medicine that often is recommended as a first-line treatment for MG. It works by increasing the amount of acetylcholine, a signaling molecule that plays a key role in muscle contraction, that is available to bind to acetylcholine receptors — the most common targets of the autoimmune attacks that disrupt nerve-muscle communication in MG.

The treatment has been approved by the U.S. Food and Drug Administration (FDA) since 1955 — before the modern concept of randomized, controlled clinical trials had emerged. That is why evidence supporting its use are based largely on retrospective data and clinical experience.

A lack of objective data from well-controlled trials hinders the understanding of the treatment’s effectiveness and side effect profile, researchers say. Further, the true effects of this “gold-standard” treatment must be established in order to compare the efficacy of new and emerging treatments.

Researchers sought to provide insight into this issue by comprehensively evaluating pyridostigmine’s use in a representative group of MG patients participating in the Dutch-Belgian myasthenia patient registry. Participants were asked to fill an online questionnaire related to their use of pyridostigmine, their perceived effectiveness of the treatment, and any side effects they experienced.

Of 391 patients who completed the entire survey, 61% were currently using pyridostigmine, 37% had used the medication previously but had since discontinued it, and 2% had never used it.

“We show that virtually all MG patients have used pyridostigmine at some point in their disease,” the researchers wrote.

Most had used higher dose

Among current users, 165 people (65%) reported they had used a higher dose in the past. The most frequently reported reasons for lowering the dose were that a higher dose was no longer needed (43%), followed by side effects (25%), and that a higher dose was not effective (17%).

Common reasons for discontinuing treatment were that it was ineffective (38%), or it was unneeded due to the start of another medication (34%). About a quarter (26%) of patients stopped using it because of side effects. Medications to help control side effects of pyridostigmine were used in 20% of all patients.

Patients rated pyridostigmine’s effectiveness on a scale ranging from 0 (no treatment effect) to 100 (complete resolution of all symptoms). The median overall effectiveness was 60 out of 100, with patients currently using pyridostigmine perceiving the treatment to be more effective than those who discontinued it.

By individual symptom, fatigue was the least responsive to treatment in both groups.

In the current use group, 55% of participants reported the effects of treatment had not changed over time, compared with 21% of those who discontinued treatment. For patients who stopped using pyridostigmine, 23% said the initial effect was good but diminished over time, while 12% said increasing doses were required over time to achieve the same effect.

Most patients using pyridostigmine (91%) said they had experienced side effects in the past week, compared with 54% of those who discontinued it or never used it. Side effects including gastrointestinal problems, urinary urgency, muscle cramps, blurred vision, sweating, salivation, light-headedness, and flu-like symptoms were more frequent among current pyridostigmine users than other survey respondents.

Unpleasant side effect

Among current users, the number of side effects was correlated with medication dose. Diarrhea was the most frequent reason for stopping or lowering the dose of pyridostigmine.

With perceived benefits and side effects under consideration, patients reported a median net benefit of pyridostigmine of 65 on a scale of 0 (”I felt much worse”) to 100 (“I felt much better”), with current users reporting a median of 73, and discontinued users a median of 49.

Final statistical analyses indicated that patients with muscle specific tyrosine kinase (MuSK) antibodies were more likely to discontinue pyridostigmine, consistent with previous findings that pyridostigmine was less effective and came with more side effects in patients with this type of MG-causing antibody.

Male users were more likely to discontinue treatment than females, “which may be explained by the fact that female patients more frequently have severe or refractory MG and male patients appear to respond better to standard care than female patients,” the researchers wrote.

Female patients more often reported side effects, including fatigue, sweating, abdominal cramps, hot flashes, and irregular heartbeat.

Overall, study findings indicate that the net benefit of pyridostigmine is moderate, and side effects are frequent.

“Remarkably, only a small number of patients experienced a very good effect of pyridostigmine on their symptoms,” the researchers wrote. “Nonetheless, pyridostigmine remains a drug that is readily available at low cost and has a very favorable long term safety profile.”

Researchers developed a patient-friendly leaflet summarizing the findings that they say can be handed out when a pyridostigmine prescription is given.