People with refractory generalized myasthenia gravis (gMG) who responded to Soliris (eculizumab) were able to reduce the use of immunosuppressive therapies, data from an extension study of the Phase 3 REGAIN trial showed.
Tapering off immunosuppressants may be considered for those with hard-to-treat gMG who respond to Soliris, the scientists said — which should ease these patients’ treatment-related burden.
The analysis was published in the journal Neuromuscular Diseases, in a study titled “Concomitant Immunosuppressive Therapy Use in Eculizumab-Treated Adults With Generalized Myasthenia Gravis During the REGAIN Open-Label Extension Study.”
Developed by Alexion Pharmaceuticals, Soliris is approved to treat gMG patients with antibodies against acetylcholine receptors (AChRs), which impair the communication between nerves and muscle cells. AChR-positive MG is the most common form of the disease.
Soliris works by blocking the activity of a protein known as C5, which is one of more than 30 proteins belonging to the complement system — part of the immune system that induces the autoimmune response seen in those with MG.
Its’ approval was based on data from the international Phase 3 REGAIN clinical trial (NCT01997229), which compared Soliris with a placebo, and an open-label extension (OLE) study (NCT02301624) that used Soliris only.
During REGAIN, sponsored by Alexion, participants were required to continue their previously established immunosuppressive treatment regimens with no changes permitted. In turn, dose adjustments were allowed throughout the OLE phase, at the discretion of the trial investigator.
Now, a team in the U.S. examined changes in the use of immunosuppressive therapies (ISTs) during REGAIN’s extension study.
Of 118 participants who completed REGAIN, 87 completed the extension study. The main causes of discontinuation among the remaining patients were side effects, and patient withdrawal and withdrawal by a physician for other reasons.
The median duration of Soliris treatment from the beginning of the OLE study to the last assessment was 972 days, or about 2.7 years.
All but one participant used at least one IST during the extension study. At the last assessment, 103 (88%) patients were using at least one IST.
A total of 719 changes in IST regimens occurred in 90 patients (76.9%), with 489 (68%) of those changes consisting of stopping or decreasing the dose of at least one IST. The remaining 230 (32%) meant starting an IST or increasing the dose of at least one IST.
During the OLE, 84 participants(71.8%) stopped or decreased the daily dose of one or more ISTs, mostly due to MG symptom easing. In turn, among the 71 patients (60.7%) who started or increased the daily dose of at least one IST, the most common reason was MG symptom worsening.
The most common IST used was the synthetic hormone prednisone and related corticosteroids (76.9%), followed by azathioprine (33.3%), and then CellCept (mycophenolate mofetil; 25.6%), both oral medicatioins. At the last assessment, fewer patients were using prednisone (65%) or azathioprine (22.2%), with little change in those using CellCept (26.5%). The percentage of patients using combinations of corticosteroids with either azathioprine or CellCept also decreased.
Almost half (47.9%) of those who used prednisone or related corticosteroids decreased or stopped the dose during the extension study, and by the last assessment, 10 of 90 (11.1%) stopped using these treatments. Significant reductions in mean daily dose were observed among all patients.
Of those who used azathioprine, 41% decreased or stopped their dose, with one third (33.3%) discontinuing azathioprine by the last assessment. Again, significant reductions in the daily dose from baseline to final evaluation were seen in all patients.
A total of 38.2% of participants decreased or stopped CellCept, and 13.3% discontinued this therapy at the last assessment. Significant dose reductions were observed among all patients as well.
Participants who had IST dose adjustments showed improvements — as measured by MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores — regardless of starting Soliris at the start of REGAIN or at the beginning of the extension study.
The only exceptions were changes in QMG total score (which reflects physician-evaluated neurologic function) in patients who increased or started prednisone or related treatments, and changes in MG-ADL total score in those who increased and or started azathioprine.
MG exacerbations, or crises, occurred in 27 patients during the OLE. Of these, nine experienced exacerbations after decreasing or stopping one of the three types of ISTs.
Soliris was well-tolerated during both REGAIN and its OLE, with headache (44.4%) as the most commonly reported adverse event, followed by the common cold (38.5%). One meningococcal infection was reported during the OLE, which was resolved with antibiotics, and three deaths occurred in participants with significant co-existing conditions.
The proportions of patients who experienced treatment-emergent adverse events were similar across the three groups of ISTs.
“These results suggest that individuals with gMG who are treated with eculizumab [Soliris] may be able to successfully reduce their IST use, which is likely to ease their treatment-related burden,” the researchers concluded. “Individualized tapering of ISTs, guided by best practice standards, should therefore be considered in patients who respond to eculizumab.”
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