Tacrolimus alone helps some MG patients reach remission: Study

The immunosuppressant tacrolimus as a standalone therapy may help adults with mild or moderate myasthenia gravis (MG) reach and maintain a state of minimal disease symptoms (remission), according to a study in China.

Patients whose symptoms began at age 70 or younger were significantly more likely to achieve remission faster with off-label tacrolimus monotherapy (TAMO), when tacrolimus was used alone. A slower tapering of tacrolimus dosage was significantly associated with lower rates of relapse, or a return of symptoms, after remission.

Despite potential benefits, variability in responses to TAMO and the frequency of potential treatment-related adverse events suggested that this treatment approach may not be appropriate for all MG patients, according to the researchers. “The decision to initiate or continue TAMO should involve a shared decision-making process,” they wrote.

The study, “Tacrolimus as Single-Agent Immunotherapy for Adult-Onset Myasthenia Gravis: Remission, Relapse, and Safety,” was published in CNS Neuroscience & Therapeutics.

MG is an autoimmune neuromuscular condition that causes muscle weakness and fatigue. MG treatment often includes corticosteroids, a group of powerful anti-inflammatory medications. While these drugs can help address excessive immune activity, their use at high doses or over a long term can cause serious side effects. Doctors often recommend tapering corticosteroid doses over time to help avoid complications.

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“To minimize the risk of disease relapse during tapering and to limit the side effects of long-term steroid treatment, many immunosuppressant medications are used as steroid-sparing agents,” the team wrote.

Tacrolimus, marketed under the brand name Prograf, among others, is one such steroid-sparing immunosuppressant. While not approved for MG, it is commonly used off label to treat the disease.

When glucocorticoids are contraindicated or the patient refuses them, doctors may prescribe tacrolimus alone. However, the efficacy of this TAMO approach for mild or moderate MG remains unclear.

To assess this, a team of researchers examined medical records from 153 adults with mild to moderate MG who received oral TAMO (initiated at a daily dose of 2 mg) for at least one month. All were followed at a single Chinese center and had the adult-onset form of MG, with symptoms first appearing at a median age of 61.

Most patients (60.1%) had new-onset MG. Participants had lived with the disease for a median of seven months and were followed for a median of 24.4 months (about two years) after TAMO initiation.

During this time, 77.8% of participants reached minimal symptom expression, or MSE, indicating MG remission. The median time to reach remission was six months.

Participants who reached MSE had significantly lower MG Activities of Daily Living scores at TAMO start than those who did not reach remission (five vs. six), meaning that the disease had less profound effects on their everyday activities. The finding suggests “that patients with severe MG may be less likely to achieve MSE with TAMO,” the researchers wrote.

Statistical analyses adjusted for potential influencing factors showed that younger age at MG onset (specifically, 70 or younger) and new-onset MG were significantly associated with a shorter time to MSE.

A total of 100 patients followed for a median of about two years after MSE were included in the relapse analysis. Nearly one-third (31%) experienced a relapse, which occurred at a median of 13.8 months (a little over one year) after MSE.

Adjusted statistical analyses showed that lower blood tacrolimus levels at MSE and a faster dose reduction were significantly associated with a shorter time to relapse. This suggests that attention to dosing protocols may be important for relapse prevention.

The effects of too-fast dose reduction were often reversible, however. “Most relapsed patients regained clinical stability after restoring the tacrolimus dosage to maintenance levels,” the team wrote.

The therapy’s safety was analyzed using data from 200 MG patients who received TAMO and were followed for a median of nearly two years. During this time, 45% experienced adverse events deemed likely related to tacrolimus. The most common of these events was high blood sugar (17.5%), which was particularly prominent in older participants. These patients “need more frequent monitoring of [blood sugar] when taking tacrolimus,” the researchers wrote.

A total of 16 people (8%) discontinued treatment due to potential tacrolimus-related adverse events.

During follow-up, eight participants (4%) developed cancer, and half of them died. This suggests that close clinical monitoring for cancer risk may be appropriate during TAMO for MG.

“Due to the limited follow-up duration in this study, longer-term studies are needed to confirm the long-term safety of TAMO, particularly regarding cancer risk,” the team wrote.

Larger studies, following patients over time and for longer periods, are needed to confirm the potential risks and benefits of TAMO in MG, as well as the predictors of remission and relapse, the researchers said.