Trial Design and Impact on Study Outcome: Post-hoc Analysis of the BeatMG Study Based on RINOMAX Trial Criteria
Objective:
To perform a post-hoc analysis of the B-cell Targeted Treatment in Myasthenia Gravis (BeatMG, NCT02110706) study with select inclusion-exclusion criteria as of the Rituximab in Patients with New-Onset Generalized MG (RINOMAX, NCT02950155) trial.
Background:
While BeatMG study showed no definitive benefit of rituximab, the RINOMAX trial demonstrated efficacy. Diverging conclusions have led to further questions as to the role of rituximab in the treatment paradigm for AChR-Ab+ MG. Some key differences in trial design between BeatMG and RINOMAX may have impacted the study findings.
Design/Methods:
We applied select RINOMAX eligibility criteria, including baseline quantitative MG (QMG) score of ≥ 6, no other IST, baseline daily prednisone dose of ≤ 40 mg, and no history of thymectomy to the BeatMG cohort to reduce the influence of high dose of prednisone, concomitant IST use, and thymectomy. Both changes in raw numbers and percentage changes in the disease severity scores from baseline were considered. Intention to treat analysis was performed with the last observation carried forward.
Results:
Ten patients in the placebo arm (56.1 ± 16.1 years, five women) and ten patients in the rituximab arm (55.9 ± 16.4 years, four women) fulfilled the modified inclusion criteria for this analysis. Patients in the rituximab arm had more severe disease. Patients in the rituximab group showed significant changes in QMG scores from baseline [for raw values (p < 0.001) and percentage changes (p 0.02)]. Prednisone dose was successfully reduced in both placebo and rituximab groups. Rituximab was successful in lowering the AChR autoantibody titer.
Conclusions:
Clinical trial design may impact the assessment of an intervention and should be considered when comparing studies. While this post-hoc analysis showed some trends of beneficial effect of rituximab in a subgroup of patients with AChR-Ab+ MG, it highlights the need to better understand the role of B cell depletion therapy in MG.