Ortho Clinical Diagnostics

Effective clinical and public health decision-making during a pandemic depends on reliable and interoperable clinical diagnostic test results. To ensure trustworthy outcomes, we need widely available calibration standards harmonized to a shared scale. We present a “playbook” for an interlaboratory harmonization study that calibrates any available standards against a limited-availability standard issued by a global authority like the World Health Organization (WHO).

Background: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a good safety/tolerability profile, in participants with moderate to severe acne. Acne clinical presentation and response to treatment may differ between males and females as well as between pediatric-postadolescent (<24 years) and adult (≥25 years) patients. The objective of this post hoc analysis was to evaluate the impact of age and sex on the efficacy and safety of CAB gel. Methods: In one phase 2 and two phase 3 double-blind, 12-week studies, participants with moderate-to-severe acne were randomized to once-daily CAB or vehicle (Veh). Data were analyzed post hoc for participants categorized by age and sex: females 9-24 or ≥25 years (ns=274 and 121) and males 9-24 or ≥25 years (ns=241 and 21). Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory and noninflammatory lesions (IL/NIL). Treatment-emergent adverse events (TEAEs) were also assessed. Results: At week 12, a greater percentage of participants in all sex/age subgroups achieved treatment success with CAB (42.3-54.1%) than Veh (15.0-22.5%). Similarly, lesion reductions were larger with CAB than Veh (IL: CAB, 75.9-77.8%; Veh, 50.8-65.2%; NIL: CAB, 69.7-73.7%; Veh, 44.5-55.2%). For all efficacy endpoints, CAB was statistically superior to Veh among males and females 9-24 years and females ≥25 years (P≤0.05, all). For males ≥25 years, only NIL reductions were significantly greater with CAB (P≤0.05), likely due to the small population. For all CAB-treated groups, most TEAEs were of mild-moderate severity. Rates of TEAEs deemed related to CAB treatment were similar for males and females 9-24 years (19.7% and 18.6%, respectively) and somewhat higher for females ≥25 years (24.4%). Considerably lower treatment-related TEAE rates in males ≥25 years (8.3%) may reflect the low number of participants in this group (n=12 treated with CAB). Conclusions: In 3 clinical trials, participants treated with CAB gel—the only fixed-dose, triple-combination topical for acne—experienced ≥70% lesion reductions, and approximately half achieved clear or almost clear skin. CAB gel demonstrated good efficacy and tolerability regardless of participants’ sex or age. Funding: Ortho Dermatologics

Background: Toenail onychomycosis treatment is challenging, especially in older adults, due to slower nail growth, increased nail thickness, and greater likelihood of concomitant medication use and comorbidities (eg, diabetes, peripheral vascular disease, reduced renal function). Unfortunately, published efficacy and safety data in older adults are limited. Efinaconazole 10% solution has demonstrated efficacy and favorable tolerability in two phase 3 studies and in post hoc analyses of participant sex, ethnicity, age, baseline disease severity, and concurrent diabetes. Here, pooled post hoc analyses were conducted to evaluate efficacy and safety of efinaconazole in participants aged ≥65 years with mild to moderate onychomycosis. Methods: Data were pooled from 2 multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (NCT01008033, NCT01007708) of participants aged 18-70 years with mild to moderate distal lateral subungual onychomycosis affecting ≥1 great toenail. Participants (n=1,655) were randomized (3:1) to topical efinaconazole 10% or vehicle applied once daily for 48 weeks, with a follow-up visit at week 52. Efficacy endpoints included rates of complete cure (0% clinical involvement of target toenail + negative potassium hydroxide [KOH] examination + negative fungal culture), mycologic cure (negative KOH + negative fungal culture), complete/almost complete cure (≤5% clinical involvement + mycologic cure), unaffected new toenail growth (change from baseline in unaffected toenail measurement), and clinical efficacy (<10% clinical involvement) at week 52. Adverse events (AEs) were also assessed. Only participants aged ≥65 years were included in these analyses (n=162 efinaconazole; n=56 vehicle). Results: At week 52, significantly more older adults treated with efinaconazole vs vehicle achieved a complete cure (13.6% vs 3.6%) or a complete/almost complete cure (19.1% vs 5.4%; P<0.05, both). Over half of participants treated with efinaconazole (59.2%) achieved mycologic cure vs 12.5% with vehicle (P<0.001). Least squares mean unaffected new nail growth was significantly greater with efinaconazole vs vehicle (3.9 mm vs 0 mm; P<0.001), and a quarter of participants achieved clinical efficacy with efinaconazole (25.3%) vs 14.3% with vehicle (P<0.05). Most treatment-emergent AEs with efinaconazole were mild to moderate in severity, and discontinuation rates were low (<4.5%), in line with the overall phase 3 populations. Conclusions: Topical efinaconazole 10% solution showed good efficacy and safety in participants aged ≥65 years with mild to moderate onychomycosis, despite possible age-related changes in nail growth. These results were in line with the overall phase 3 populations, demonstrating that efinaconazole is an efficacious treatment for older adults for whom there is a dearth of clinical data. Funding: Ortho Dermatologics

Background: Topical treatment of acne—particularly with retinoids—often incurs a transient period of dermal irritation characterized by erythema, scaling, and other dermal changes that may reflect the same mechanisms of action by which acne pathophysiology is addressed. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a safety/tolerability profile typical of topical acne treatment. The objective of this post-hoc analysis is to determine whether CAB efficacy was related to occurrence of cutaneous safety/tolerability events. Methods: Data were pooled from 4 double-blind, 12-week studies of participants with moderate-to-severe acne. Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). Cutaneous safety/tolerability assessments of erythema and scaling (investigator-assessed) and itching, burning, and stinging (participant-assessed) were graded on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). To determine if CAB efficacy was associated with cutaneous events, efficacy endpoints at week 12 were compared for CAB-treated participants who experienced no increase versus ≥1-grade (any) increase in any safety/tolerability score at weeks 2, 4, or 8. Results: At week 12, CAB-treated participants experiencing any safety/tolerability event (n=411) had significantly greater rates of treatment success and IL reductions, and numerically greater NIL reductions, than those without events (n=188; treatment success: 55.0% vs 43.0%; P<0.01; IL reductions: 79.1% vs 72.3%; P<0.001; NIL reductions: 73.1% vs 68.1%). At weeks 2, 4, and 8, IL/NIL reductions were significantly greater among participants experiencing any cutaneous event than those without events (P<0.05, all). Overall, improved efficacy appeared to be driven by events of scaling, itching, and burning. Conclusions: Across four clinical studies, CAB-treated participants who experienced safety/tolerability events at weeks 2, 4, or 8 also experienced greater lesion reductions across 12 weeks of treatment and greater rates of treatment success at week 12. These findings are consistent with the theory that early instances of cutaneous irritation during topical acne treatment may reflect therapeutic mechanisms of action. Setting patient expectations regarding the potential for transient irritation during treatment may contribute to greater adherence and efficacy with CAB gel. Funding: Ortho Dermatologics

Background: Triple-combination therapies for acne including an antibiotic, topical retinoid, and benzoyl peroxide (BPO) are more effective than dual combinations or topical monotherapy. In clinical studies of participants with moderate to severe acne, clindamycin phosphate (CLIN) 1.2%/adapalene (ADAP) 0.15%/BPO 3.1% (CAB) gel demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability. Because acne pathogenesis and presentation can vary by skin type and ethnicity, it is important to assess treatment outcomes for specific populations. This post hoc analysis assessed efficacy and safety of CAB gel in Caucasian participants. Methods: Data were pooled from two phase 2 and two phase 3 double-blind, 12-week studies of participants with moderate to severe acne (N=1787). The pooled population included 1283 self-identified Caucasian participants, randomized to 6 treatment arms: once-daily CAB gel (n=446), ADAP 0.15%/BPO 3.1% gel (n=109), CLIN 1.2%/BPO 3.1% gel (n=101), CLIN 1.2%/ADAP 0.15% gel (n=109), branded ADAP 0.3%/BPO 2.5% gel (n=165), and vehicle (n=353). Endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory/noninflammatory lesions. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. Results: At week 12, a significantly greater percentage of Caucasian participants achieved treatment success with CAB gel (51.5%) than dyads (range, 31.7%-34.3%), randed ADAP 0.3%/BPO 2.5% gel (33.5%), or vehicle (17.9%; P<0.01, all). CAB yielded significantly greater reductions from baseline in inflammatory and noninflammatory lesions (76.8% and 73.0%, respectively) than dyads (62.7%-70.2% and 60.9%-63.4%, P<0.01, all), randed ADAP 0.3%/BPO 2.5% gel (72.6% and 65.7%, P<0.05, both) and vehicle (52.3% and 44.8%, P<0.001, both). Most TEAEs were of mild to moderate severity; the most common treatment-related TEAEs were application site pain, dryness, dermatitis, and erythema. Transient increases in cutaneous safety/tolerability scores beginning at week 2 resolved back to or near baseline by week 12; all scores were <1 (mild) at all post-baseline assessments. Conclusions: In Caucasian participants with moderate to severe acne across 4 clinical studies, triple-combination CAB gel demonstrated significantly greater efficacy without worsening tolerability vs dyad gels, randed ADAP 0.3%/BPO 2.5% gel, or vehicle. Funding: Ortho Dermatologics