SB206, a Nitric Oxide-Releasing Topical Medication, Induces the Beginning of the End Sign and Molluscum Clearance

Abstract

The beginning of the end (BOTE) sign has been proposed to describe well-recognized clinical signs of inflammation (including erythema, induration, and scale) that predict imminent resolution of molluscum contagiosum (MC). This phenomenon has never been prospectively studied. An integrated analysis of two prospective, 12-week, randomized, double-blind clinical trials of topical nitric oxide-releasing SB206 gel evaluated an association between BOTE sign and MC lesion reduction. Of 707 randomized patients, ~80% exhibited BOTE signs regardless of treatment assignment. At week 12, MC lesion counts decreased from baseline by 50.7% for baseline BOTE+ versus 29.1% for BOTE- (P = 0.0015) vehicle-treated patients compared with a 63.3% decrease for baseline BOTE+ versus 51.7% for BOTE- (P = 0.0194) SB206-treated patients. Among vehicle-treated patients, 48 (22.3%) who were never BOTE+ had an 18.5% reduction from baseline in MC lesion counts versus a 34.0% reduction in 165 patients (76.7%) who experienced BOTE at any time, suggesting that the projected duration of lesion clearance for patients with 18-20 MC lesions is 15 months for BOTE- versus 6 months for BOTE+ patients. Patients who were both BOTE+ and treated with SB206 had the greatest reduction in MC lesion count. SB206 may trigger BOTE signs and shorten the duration of MC infection. The two studies whose data are analyzed in this study are registered at ClinicalTrials.gov with the identifiers NCT03927703 and NCT03927716.

Keywords: BOTE, beginning of the end; MC, molluscum contagiosum; NO, nitric oxide; TEAE, treatment-emergent adverse event; Th, T helper.

© 2021 The Authors.

Figures

Figure 1

Example of a BOTE sign. (a) An SB206 clinical trial patient at baseline, week 4, and week 12. Local skin reaction may coexist at week 4. (b) A spontaneous BOTE sign observed in a regular clinical practice patient (not in SB206 MC clinical trials). Patient consent was obtained for the publication of these images. BOTE, beginning of the end; MC, molluscum contagiosum.

Figure 2

Percentage of BOTE+ patients by week (integrated safety population). The percentage of BOTE+ patients was highest at week 4 for both SB206- and vehicle-treated groups, with a greater percentage of BOTE+ patients in the SB206 group. Integrated safety population: SB206, n = 472; vehicle, n = 233. BOTE, beginning of the end; QD, once daily.

Figure 3

Change in BOTE grade by visit (integrated ITT population). The percentage of patients who demonstrated ≥1-point BOTE score increase from baseline was 28.9%, 31.7%, and 31.2% in the vehicle-treated group compared with 57.3%, 61.3%, and 43.9% in the SB206-treated group at weeks 2, 4, and 8, respectively. The between-group difference for this parameter decreased by week 12 (27.3% vs. 32.2%). Integrated ITT population: SB206, n = 473; vehicle, n = 234. BOTE, beginning of the end; ITT, intention-to-treat; QD, once daily.

Figure 4

Erythema component score of medication-related LSRs over time. Patients treated with SB206 showed higher LSR composite scores than patients treated with vehicle. The LSR composite score, primarily driven by erythema, peaked at week 2 or 4 and began to steadily decline through week 12. Integrated safety population: SB206, n = 472; vehicle, n = 233. The number of observed patients in each group at each time point is shown within each bar (n/N). The positive sign (+) includes erythema scores of 1, 2, 3, or 4. LSR, local skin reaction; QD, once daily.

Figure 5

LS mean percentage change from baseline in MC lesion count over time by baseline BOTE score for integrated ITT population. Vehicle-treated baseline BOTE+ patients showed a greater reduction in lesion count than vehicle-treated baseline BOTE– patients. Over time, patients treated with SB206 showed a greater reduction in lesion count than those treated with vehicle regardless of BOTE status at baseline, whereas SB206-treated patients who were BOTE+ at baseline showed a greater reduction in lesion count than SB206-treated patients who were BOTE– at baseline. Integrated ITT population: SB206, n = 473; vehicle, n = 234. BOTE, beginning of the end; ITT, intention-to-treat; LS, least square; MC, molluscum contagiosum; QD, once daily; SE, standard error.

Figure 6

Week 12 mean percentage change from baseline in MC lesion count by week 2 BOTE status. Percentage change from baseline in lesion count at week 12 was compared on the basis of the week 2 BOTE status (Figure 6). In the vehicle-treated group, the mean percentage lesion count reduction at week 12 was 13.6% for BOTE– patients (n = 115; 54.2%) compared with 49.4% for BOTE+ patients (n = 97; 45.8%) at week 2. In the SB206-treated group, the mean percentage lesion count reduction at week 12 was 38.2% for BOTE– patients (n = 164; 42.1%) and 61.4% for BOTE+ patients (n = 226; 57.9%) at week 2. The magnitude of the percentage reduction from baseline in MC counts at week 12 was greater for patients who were BOTE+ at week 2 in both groups but highest in the SB206-treated group, regardless of week 2 BOTE status. Integrated ITT population: SB206, n = 473; vehicle, n = 234. BOTE, beginning of the end; ITT, intention-to-treat; LS, least square; MC, molluscum contagiosum; QD, once daily; SE, standard error.

Figure 7

Week 12 mean percentage change in MC lesion count by maximum postbaseline BOTE status. Percentage change in lesion counts between baseline and week 12 was compared by the highest postbaseline BOTE status at any visit. In the vehicle-treated group, there was a 22.0% mean percentage reduction from baseline in lesion counts for patients who were BOTE– after baseline (n = 59; 27.4%), compared with a 33.8% mean reduction for patients with any detectable postbaseline BOTE inflammation (n = 156; 72.6%). In the SB206-treated group, these mean percentage reductions and patient numbers were 39.6% (n = 72; 18.1%) and 54.9% (n = 325; 81.9%) for BOTE– and BOTE+ patients, respectively. Integrated ITT population: SB206, n = 473; vehicle, n = 234. BOTE, beginning of the end; ITT, intention-to-treat; LS, least square; MC, molluscum contagiosum; QD, once daily; SE, standard error.