https://orcid.org/0009-0009-0184-2553
TO THE EDITOR:
We commend the authors for conducting this randomized, multicenter trial “Efficacy and Safety of DAPSone as a Second-line Option in Adult Immune Thrombocytopenia (DAPS-ITP).1 The authors present a valuable perspective; however, we would like to discuss a few concerns about the study design and the statistical analysis.
The authors reported a high dapsone discontinuation rate owing to adverse event rates of 41.3% (clinical trial) and 21.7% (observational study), which is higher than the dapsone discontinuation rate of ∼10% previously reported by them.2,3 This was most probably a consequence of the strict stopping rules. Many patients met the stopping rule, which was unsurprising because the authors previously reported a hemoglobin fall of >1.5 g/dL among ∼50% of patients; Godeau et al and Colella et al have reported hemoglobin falls of 1.71 g/dL (standard deviation, 1.22) and 1.7 g/dL (range, 0.9-2.9), respectively.2,4 Thus, the study retained patients with minimum to no hemolysis who were likely to be nonresponders, based on the association between a higher hemoglobin drop and dapsone response,2,4,5 thereby introducing a selection bias. Dapsone discontinuation in 10.9% of asymptomatic patients with methemoglobinemia could have been avoided, because most patients have been reported to remain asymptomatic (95.9%) despite high methemoglobin levels (83%).4
Because of the high withdrawal rates, only 10 patients (21.7%) were retained at week 52 in both studies. The missing platelet count data reduced the sample size further to 8 for the observational study. Neither intent-to-treat nor per-protocol analysis is reliable when there is such a large withdrawal rate.6
There was inconsistency in reporting the dapsone discontinuation rate owing to severe adverse events (arm A) with 66.7% being reported in the abstract, 63% (29/46) being reported in figure 2, and 41.3% (19/46) being reported in table 2 and the results section.
In conclusion, the study lacks internal validity because of the high withdrawal rate and missing data. Thus, the findings should be validated with an appropriately designed and adequately powered study.
Contribution: A.P. and A.V. were responsible for conceptualization and drafted the manuscript; S.D.S. and A.V. performed the literature review; and all authors reviewed and approved the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Ashwin Patel, Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Dr, Atlanta, GA 30322; email: apat261@emory.edu.
