Data from the secondary analysis show that the improvements seen in health-related quality of life (HRQOL) translated into clinical improvements.
An analysis of efgartigimod has demonstrated the positive impact of the treatment on health-related quality of life (HRQOL) in patients with generalized myasthenia gravis (MG).
The findings come from a secondary analysis of the phase 3 ADAPT study, which led to the 2021 approval of intravenous efgartigimod, the first of a new class of treatments—neonatal Fc receptor antagonists—for the rare neuromuscular disorder. The FDA recently granted priority review for a subcutaneous formulation of the treatment for patients, with an expected PDUFA date of March 30 of this year.
Data from this secondary analysis published in Journal of Neurology showed that the improvements in HRQOL also translated into clinical improvements, with increases in symptom scores across the patients with acetylcholine receptor antibody–positive (AChR-Ab+) generalized MG who received 2 cycles of treatment. The researchers noted that other studies of MG treatments have shown clinical improvements without favorable implications for HRQOL, suggesting that analyzing clinical manifestations alone may not give the full picture of the burden of MG.
“Given such findings, HRQOL measures are becoming increasingly important for evaluating the benefit of therapeutic interventions. They have historically been undervalued both in clinical studies of generalized MG and in clinical practice, where treatment intent has been primarily focused on preventing hospitalization. These measures, however, better assess the full burden of disease experienced by individuals with generaliuzed MG,” the study authors wrote. “Regulatory bodies have also recognized the importance of patient-reported outcome measures, including HRQOL, and are increasingly using these data to support label claims and reimbursement decisions.”
There were 129 patients with AChR-Ab+ MG included in the analysis, with 65 randomized to receive efgartigimod and 64, placebo. Even among the patients with poor HRQOL scores at baseline, efgartigimod yielded significant and rapid improvements in scores of Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r), in all 5 dimensions of the EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L), and in scores of the EQ-5D-5L visual analog scale. Improvements were seen as early as the first week of treatments and were maintained through up to 4 weeks of follow-up.
The researchers highlighted the low EQ-5D-5L health utility scores seen among the patients at baseline despite being on stable treatment, with the majority reporting issues with mobility, usual activities, and self-care. Patients also indicated pain and discomfort, anxiety, and depression.
These improvements in HRQoL throughout treatment were coupled with improvements in immunoglobulin G (IgG) level and the pattern of improvements in HRQOL measures were consistent with those observed across other efficacy measures. The group observed the maximum benefit at week 4 or 5 in each treatment cycle, which was similar to the time of greatest change in IgG level. The researchers noted that the start of clinical benefit with efgartigimod was coupled with a drop in IgG titer, although clinical myasthenic symptoms returned approximately 3 weeks after the increase in IgG titer.
“The study did not include formal data analysis of AChR-Ab− [negative] participants due to the small sample size; the study was not powered to demonstrate statistically significant differences between the efgartigimod and placebo groups in the AChR-Ab− population,” wrote the researchers. “There were 38 patients included in the analysis who were AChR-Ab−. However, results for MG-QOL15r and EQ-5D-5L were similar for the overall efgartigimod group (AChR-Ab+ and AChR-Ab−), indicating that there were no substantial differences between the AChR-Ab+ and AChR-Ab− populations.”
They recommend that future studies that utilize real-world data are needed “to further validate the benefit on HRQOL of efgartigimod in generalized myasthenia gravis.”
Saccà F, Barnett C, Vu T, et al. Efgartigimod improved health‐related quality of life in generalized myasthenia gravis: results from a randomized, double‐blind, placebo‐controlled, phase 3 study (ADAPT). J Neurol. Published online January 4, 2023. doi:10.1007/s00415-022-11517-w