IV Methylprednisolone, Tacrolimus Effective in Prednisone-Resistant Ocular MG

New study findings suggest that a common glucocorticoid and a nonsteroidal immunosuppressive treatment could both be effective options in patients with ocular myasthenia gravis (OMG) not responding to traditional first-line treatment.

Researchers have retrospectively analyzed data from a group of 57 patients with OMG not adequately responding to oral prednisone, finding that both intravenous methylprednisolone (IVMP) and tacrolimus monotherapy helped reduce symptoms.

“Oral prednisone has been recognized as the first-line therapy for the treatment of OMG. Nevertheless, its long-term use is complicated by numerous adverse effects and some OMG patients reported limited efficacy following the conventional prednisone treatment,” explained the researchers in Orphanet Journal of Rare Diseases. “New therapies urgently need to be tried. High-dose IVMP therapy has proved to own advantages in [generalized myasthenia gravis] because of rapid improvement and long-term efficacy, allowing a reduction in maintenance prednisolone doses and related adverse effects.”

Businessman with myasthenia gravis

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The researchers noted that exact information on the dose and cumulative dose of oral prednisone prior to study treatment was not complete.

The 57 patients, 29 receiving IVMP and 28 receiving tacrolimus, were followed for at least 6 months and experienced significant improvements in symptoms, with no statistical differences between the 2 groups at the end of follow-up. Clinical improvement in the study was defined as at least a 2-point decrease in ocular qualitative MG (QMG) score. More patients receiving IVMP than tacrolimus achieved the cut-off mark at 1 (51.7% vs 12%), 3 (69% vs 40%), and 6 (69% vs 46.4%) months of treatment.

After the first month of treatment, changes in QMG score were higher among patients receiving IVMP than those receiving tacrolimus, with a median change of 2 vs 0. However, by 3 months, changes in scores were higher among patients receiving tacrolimus, with a median change of 2 vs 1, suggesting more rapid onset of the IVMP and a more delayed effect of tacrolimus. The researchers noted that other nonsteroidal treatments, including azathioprine and mycophenolate mofetil, also typically require multiple months of treatment before they demonstrate efficacy.

Multivariate analysis of the IVMP group revealed that having higher ocular QMG scores at baseline predicted a better response to the treatment (OR, 1.781, 95% CI, 1.066-2.975; P = .028).

The researchers noted that, across both treatment groups, symptoms tended to stabilize as treatment progressed. For both groups, changes in ocular QMG scores were more pronounced in the previous 3 months while changes in scores decreased at 6 months.

Throughout treatment, adverse effects (AEs) were tolerable and transient, with 5 AEs reported among patients receiving IVMP and 11 reported among patients receiving tacrolimus. There were no serious AEs observed in either group.

Patients were a median age of 20 years, and their median course of disease was 96 months—a median of 120 months in the IVMP group and 42 months in the tacrolimus group. Within the IVMP group, 10 patients received 500 mg daily while 18 received 1000 mg daily at the start of treatment.

“Protocols of IVMP treatment for MG are remarkably different. In one study, 1000 mg per day of MP was repeatedly administered monthly; in another study, 3 days of 250 mg, 500 mg, or 1000 mg IVMP was administered weekly. MP was intravenously at a dose of 1-2 g/day in most studies, without dose de-escalation. In our study, the initial dose of MP was 500 mg or 1000 mg per day and was then reduced by half every 2-3 days. Subtle differences existed in the dosage of MP among patients, but there was no significant difference in therapeutic efficacy between patients with different dosages of MP (initial dose, 500 mg vs 1000 mg; P = .244).”

The group hypothesized that one driver of the absence of significant efficacy differences could be disease severity at presentation, with higher doses of MP more commonly used when symptoms were more apparent aggressive.

Reference

Zhang KY, Duan WW,Luo YB, Li Y, Hu J, Yang H. Comparative effectiveness and safety of intravenous methylprednisolone and tacrolimus monotherapy in ocular myasthenia gravis with unsatisfactory prednisone responses: a retrospective study. Orphanet J Rare Dis. Published online January 19, 2024. doi:10.1186/s13023-024-03025-z