Poor evidence for an effect of tecovirimat in shortening recovery time in hospitalized mpox cases from real-world data

ObjectivesTo assess the effectiveness of tecovirimat (TPOXX) for treating mpox in terms of difference in healing time and extent of viral clearance. DesignEmulation of a target trial based on observational data. SettingItaly ParticipantsForty-one men hospitalized for mpox as of September 29th, 2022. Main outcome measuresMain outcome was the time to clinical recovery. Secondary outcome was the variation in viral load in the upper respiratory tract (URT) after treatment. ResultsThe median time from symptoms onset to hospital admission and to initiation of TPOXX was 4 days (IQR 2-6) and 10 days (IQR 8-11), respectively. Fifteen patients completed a course of therapy. No deaths were observed; the overall median healing time was 21 days (IQR 17-26). We found no evidence for a significant improvement in recovery time in treated vs. untreated patients, with an estimated mean of 14.7 days for both groups. A subset of 13 patients had URT samples at T1 (median of 5 days (IQR 3-7) from symptoms onset) and T2 (median 7 days (IQR 7-9) from T1). Overall, mean viral load was 4.65 (0.30) vs. 4.91 (0.35) (log2 scale of cycle threshold) at T1 and T2, respectively. In the unadjusted analysis, variation over T1-T2 was lower in the treated 0.13 log2 (SD=0.53) vs. untreated 0.37 (0.50), although not statistically significant (unpaired t-test p=0.41). After controlling for confounding, there was no evidence for a difference in the potential changes over T1-T2 by treatment arm, and our estimate of the average treatment effect (ATE) was consistent with no difference by treatment group, although with large 95% CI around these estimates. ConclusionsOur analysis seems to exclude a clinically important effect of TPOXX in hospitalized mpox patients when compared to no treatment. These data are one of the valuable currently available sources of evidence to guide treatment decisions in patients hospitalized with TPOXX. Pending more robust data from randomized comparisons, the use of TPOXX should be restricted to the clinical trials setting. Trial registration"MpoxCohort" observational study protocol: approval number 40z, Register of Non-Covid Trials 2022.