s or when those therapies are not advisable. 1.2 nonsegmental vitiligo opzelura is indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older. 1.3 limitations of use use of opzelura in combination with therapeutic biologics, other jak inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.

n, including localized infections. consider the risks and benefits of treatment prior to initiating opzelura in patients: with chronic or recurrent infection with a history of a serious or an opportunistic infection who have been exposed to tuberculosis who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection. closely monitor patients for the development of signs and symptoms of infection during and after treatment with opzelura. interrupt opzelura if a patient develops a serious infection, an opportunistic infection, or sepsis. do not resume opzelura until the infection is controlled. tuberculosis no cases of active tuberculosis (tb) were reported in clinical trials with opzelura. cases of active tb were reported in clinical trials of oral janus kinase inhibitors used to treat inflammatory conditions. consider evaluating patients for latent and active tb infection prior to administration of opzelura. during opzelura use, monitor patients for the development of signs and symptoms of tb. viral reactivation viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with janus kinase inhibitors used to treat inflammatory conditions including opzelura. if a patient develops herpes zoster, consider interrupting opzelura treatment until the episode resolves. hepatitis b and c the impact of janus kinase inhibitors used to treat inflammatory conditions including opzelura on chronic viral hepatitis reactivation is unknown. patients with a history of hepatitis b or c infection were excluded from clinical trials. hepatitis b viral load (hbv-dna titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic hbv infections taking oral ruxolitinib. opzelura initiation is not recommended in patients with active hepatitis b or hepatitis c. 5.2 mortality in a large, randomized, postmarketing safety study of an oral jak inhibitor in rheumatoid arthritis (ra) patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the jak inhibitor compared with tnf blockers. consider the benefits and risks for the individual patient prior to initiating or continuing therapy with opzelura. 5.3 malignancy and lymphoproliferative disorders malignancies, including lymphomas, were observed in clinical trials of oral jak inhibitors used to treat inflammatory conditions. patients who are current or past smokers are at additional increased risk. malignancies, including lymphomas, have occurred in patients receiving jak inhibitors used to treat inflammatory conditions. in a large, randomized, postmarketing safety study of an oral jak inhibitor in ra patients, a higher rate of malignancies (excluding non-melanoma skin cancer) was observed in patients treated with the jak inhibitor compared to those treated with tnf blockers. a higher rate of lymphomas was observed in patients treated with the jak inhibitor compared to those treated with tnf blockers. a higher rate of lung cancers was observed in current or past smokers treated with the jak inhibitor compared to those treated with tnf blockers. in this study, current or past smokers had an additional increased risk of overall malignancies. consider the benefits and risks for the individual patient prior to initiating or continuing therapy with opzelura, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment , and patients who are current or past smokers. non-melanoma skin cancers non-melanoma skin cancers including basal cell and squamous cell carcinoma have occurred in patients treated with opzelura. perform periodic skin examinations during opzelura treatment and following treatment as appropriate. exposure to sunlight and uv light should be limited by wearing protective clothing and using broad-spectrum sunscreen. 5.4 major adverse cardiovascular events (mace) in a large, randomized, postmarketing safety study of an oral jak inhibitor in ra patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (mace) defined as cardiovascular death, non-fatal myocardial infarction (mi), and non-fatal stroke was observed with the jak inhibitor compared to those treated with tnf blockers. patients who are current or past smokers are at additional increased risk. consider the benefits and risks for the individual patient prior to initiating or continuing therapy with opzelura, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. discontinue opzelura in patients that have experienced a myocardial infarction or stroke. 5.5 thrombosis thromboembolic events were observed in clinical trials with opzelura. thrombosis, including deep vein thrombosis (dvt), pulmonary embolism (pe), and arterial thrombosis have been reported in patients receiving jak inhibitors used to treat inflammatory conditions. many of these adverse reactions were serious and some resulted in death. in a large, randomized, postmarketing safety study of an oral jak inhibitor in ra patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, dvt, and pe were observed compared to those treated with tnf blockers. avoid opzelura in patients who may be at increased risk of thrombosis. if symptoms of thrombosis occur, discontinue opzelura and evaluate and treat patients appropriately. 5.6 thrombocytopenia, anemia, and neutropenia thrombocytopenia, anemia, and neutropenia were reported in the clinical trials with opzelura. consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with opzelura. perform cbc monitoring as clinically indicated. if signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue opzelura. 5.7 lipid elevations treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (ldl) cholesterol, and triglycerides.

ider [see clinical studies ( 14.1 )] . 2.3 recommended dosage for nonsegmental vitiligo instruct patients to apply a thin layer of opzelura twice daily to affected areas of up to 10% body surface area. satisfactory patient response may require treatment with opzelura for more than 24 weeks. if the patient does not find the repigmentation meaningful by 24 weeks, the patient should be re‑evaluated by the healthcare provider [see clinical studies ( 14.2 )] .

-ad2), 499 adult and pediatric subjects 12 years of age and older with atopic dermatitis were treated with opzelura twice daily for 8 weeks. in the opzelura group, 62% of subjects were females, and 71% of subjects were white, 23% were black, and 4% were asian. the adverse reactions reported by ≥ 1% of opzelura treated subjects and at a greater incidence than in the vehicle arm are listed in table 1. table 1: adverse reactions occurring in ≥ 1% of subjects treated with opzelura for atopic dermatitis through week 8 in true-ad1 and true-ad2 adverse reaction opzelura (n = 499) n (%) vehicle (n = 250) n (%) subjects with any teae teae – treatment emergent adverse events 132 (27) 83 (33) nasopharyngitis 13 (3) 2 (1) bronchitis 4 (1) 0 (0) ear infection 4 (1) 0 (0) eosinophil count increased 4 (1) 0 (0) urticaria 4 (1) 0 (0) diarrhea 3 (1) 1 (< 1) folliculitis 3 (1) 0 (0) tonsillitis 3 (1) 0 (0) rhinorrhea 3 (1) 1 (< 1) adverse reactions that occurred in true-ad1 and true-ad2 in < 1% of subjects in the opzelura group and none in the vehicle group were: neutropenia, allergic conjunctivitis, pyrexia, seasonal allergy, herpes zoster, otitis externa, staphylococcal infection, and acneiform dermatitis. nonsegmental vitiligo in two double-blind, vehicle-controlled clinical trials (true-v1 and true-v2), 449 adult and pediatric subjects 12 years of age and older with nonsegmental vitiligo were treated with opzelura twice daily for 24 weeks. in the opzelura group, 55% of subjects were females, and 81% of subjects were white, 5% were black, and 4% were asian. the adverse reactions reported by opzelura treated subjects with an incidence of ≥ 1% and at least 1% greater incidence than in the vehicle arm in the 24-week double-blind period are listed in table 2. table 2: adverse reactions occurring in ≥ 1% of subjects treated with opzelura for nonsegmental vitiligo through week 24 in true-v1 and true-v2 adverse reaction opzelura (n = 449) n (%) vehicle (n = 224) n (%) subjects with any teae teae – treatment emergent adverse events 214 (48) 79 (35) application site acne 26 (6) 2 (1) application site pruritus 23 (5) 6 (3) nasopharyngitis 19 (4) 5 (2) headache 17 (4) 6 (3) urinary tract infection 7 (2) 1 (< 1) application site erythema 7 (2) 1 (< 1) pyrexia 6 (1) 0 adverse reactions that occurred in true-v1 and true-v2 in ≥ 0.5% to < 1% of subjects in the opzelura group and none in the vehicle group were: application site dermatitis, hypertension, anxiety, application site discoloration, application site folliculitis, contusion, dermatitis contact, diarrhea, ear infection, gastritis, gastroenteritis, hordeolum, influenza-like illness, insomnia, nasal congestion, and vomiting.

the background risk in the u.s. general population of major birth defects and miscarriage is 2-4% and 15-20%, respectively. data animal data ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. there were no treatment-related malformations at any dose. a decrease in fetal weight of approximately 9% was noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. this dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (mrhd; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitis-affected body surface area is used for calculation of multiples of human exposure). in rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. this dose resulted in systemic exposure approximately 70% the mrhd clinical systemic exposure. in a pre-and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. there were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the mrhd clinical systemic exposure). 8.2 lactation risk summary there are no data on the presence of ruxolitinib in human milk, the effects on the breastfed child, or the effects on milk production. ruxolitinib was present in the milk of lactating rats (see data ) . when a drug is present in animal milk, it is likely that the drug will be present in human milk. because of the serious adverse findings in adults, including risks of serious infections, thrombocytopenia, anemia, and neutropenia, advise women not to breastfeed during treatment with opzelura and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives). data lactating rats were administered a single dose of [14c]-labeled ruxolitinib (30 mg/kg) on postnatal day 10, after which plasma and milk samples were collected for up to 24 hours. the auc for total radioactivity in milk was approximately 13 times the maternal plasma auc. additional analysis showed the presence of ruxolitinib and several of its metabolites in milk, all at levels higher than those in maternal plasma. 8.4 pediatric use atopic dermatitis the safety and effectiveness of opzelura for the topical treatment of mild-to-moderate atopic dermatitis have been established in pediatric patients aged 12 to 17 years of age. use of opzelura in this age group is supported by evidence from true-ad1 and true-ad2, which included 92 pediatric subjects aged 12 to 17 years with mild-to-moderate atopic dermatitis [see clinical pharmacology ( 12.3 ) and clinical studies ( 14.1 )] . no clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects. the safety and effectiveness of opzelura in pediatric patients younger than 12 years of age with atopic dermatitis have not been established. nonsegmental vitiligo the safety and effectiveness of opzelura for the topical treatment of nonsegmental vitiligo have been established in pediatric patients aged 12 to 17 years of age. use of opzelura in this age group is supported by evidence from true-v1 and true-v2, which included 55 pediatric subjects aged 12 to 17 years with nonsegmental vitiligo [see clinical studies ( 14.2 ) ] . no clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects. the safety and effectiveness of opzelura in pediatric patients younger than 12 years of age with nonsegmental vitiligo have not been established. juvenile animal toxicity data oral administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures. when administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures [e.g., bone mineral content, peripheral quantitative computed tomography, and x-ray analysis] occurred at doses ≥ 5 mg/kg/day. when administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period. these findings were observed at systemic exposures that are at least 40% the mrhd clinical systemic exposure. 8.5 geriatric use of the 1249 total subjects with atopic dermatitis in clinical trials with opzelura, 115 (9%) were 65 years of age and older [see clinical studies ( 14.1 ) ] . no clinically meaningful differences in safety or effectiveness were observed between subjects less than 65 years and subjects 65 years and older. of the 831 total subjects enrolled with nonsegmental vitiligo in clinical trials with opzelura, 65 (8%) were 65 years of age and older [see clinical studies ( 14.2 )] . clinical trials of opzelura in subjects with nonsegmental vitiligo did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

d miscarriage is 2-4% and 15-20%, respectively. data animal data ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. there were no treatment-related malformations at any dose. a decrease in fetal weight of approximately 9% was noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. this dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (mrhd; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitis-affected body surface area is used for calculation of multiples of human exposure). in rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. this dose resulted in systemic exposure approximately 70% the mrhd clinical systemic exposure. in a pre-and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. there were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the mrhd clinical systemic exposure).

included 55 pediatric subjects aged 12 to 17 years with nonsegmental vitiligo [see clinical studies ( 14.2 ) ] . no clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects. the safety and effectiveness of opzelura in pediatric patients younger than 12 years of age with nonsegmental vitiligo have not been established. juvenile animal toxicity data oral administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures. when administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures [e.g., bone mineral content, peripheral quantitative computed tomography, and x-ray analysis] occurred at doses ≥ 5 mg/kg/day. when administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period. these findings were observed at systemic exposures that are at least 40% the mrhd clinical systemic exposure.

ly 1.5 mg/cm 2 of opzelura (dose range was approximately 1.2 grams to 37.6 grams per application) twice daily for 28 days. absorption plasma concentrations of ruxolitinib were quantifiable in all subjects. in adult subjects, the mean ± sd maximum plasma concentration (c max ) and area under the concentration time curve from 0 to 12 hours post dose (auc 0 – 12 ) for ruxolitinib on day 1 were 449 ± 883 nm and 3215 ± 6184 h*nm, respectively. there is no evidence of ruxolitinib accumulation after daily application of opzelura for 28 days in subjects with atopic dermatitis. distribution plasma protein binding is approximately 97%. elimination the mean terminal half-life of ruxolitinib following topical application of opzelura was estimated in 9 subjects and is approximately 116 hours. metabolism ruxolitinib is primarily metabolized by cyp3a4 and to a lesser extent by cyp2c9 in vitro. excretion ruxolitinib and its metabolites are primarily excreted by urine (74%) and feces (22%). less than 1% is excreted as unchanged drug. specific populations pediatric patients in adolescent subjects with atopic dermatitis (13 – 17 years of age), the mean ± sd c max and auc 0 – 12 for ruxolitinib on day 1 were 110 ± 255 nm and 801 ± 2019 h*nm, respectively. drug interactions clinical studies drug interaction studies with opzelura have not been conducted. strong cyp3a4 inhibitors the c max and auc of ruxolitinib increased 33% and 91%, respectively, with administration of 10 mg single dose orally following ketoconazole 200 mg twice daily for four days, compared to receiving the oral ruxolitinib dose alone in healthy subjects. mild or moderate cyp3a4 inhibitors there was an 8% and 27% increase in the c max and auc of ruxolitinib, respectively, with the administration of 10 mg single dose orally following erythromycin, a moderate cyp3a4 inhibitor, at 500 mg twice daily for 4 days, compared to receiving the oral ruxolitinib dose alone in healthy subjects. there are no clinical studies conducted with mild cyp3a4 inhibitor. cyp3a4 inducers the c max and auc of ruxolitinib decreased 32% and 61%, respectively, with the oral administration of 50 mg single dose of ruxolitinib following rifampin 600 mg once daily for 10 days, compared to receiving the oral ruxolitinib dose alone in healthy subjects. in vitro studies cytochrome p450 (cyp) enzymes: ruxolitinib is not expected to inhibit cyp1a2, 2b6, 2c8, 2c9, 2c19, 2d6 and cyp3a4 or induce cyp1a2, 2b6 and 3a4 following topical application. transporter systems: ruxolitinib is not expected to inhibit p-gp, bcrp, oatp1b1, oatp1b3, oct1, oct2, oat1, or oat3 transporter systems following topical application. ruxolitinib is not a substrate for the p-gp transporter.

cal application of opzelura was estimated in 9 subjects and is approximately 116 hours. metabolism ruxolitinib is primarily metabolized by cyp3a4 and to a lesser extent by cyp2c9 in vitro. excretion ruxolitinib and its metabolites are primarily excreted by urine (74%) and feces (22%). less than 1% is excreted as unchanged drug. specific populations pediatric patients in adolescent subjects with atopic dermatitis (13 – 17 years of age), the mean ± sd c max and auc 0 – 12 for ruxolitinib on day 1 were 110 ± 255 nm and 801 ± 2019 h*nm, respectively. drug interactions clinical studies drug interaction studies with opzelura have not been conducted. strong cyp3a4 inhibitors the c max and auc of ruxolitinib increased 33% and 91%, respectively, with administration of 10 mg single dose orally following ketoconazole 200 mg twice daily for four days, compared to receiving the oral ruxolitinib dose alone in healthy subjects. mild or moderate cyp3a4 inhibitors there was an 8% and 27% increase in the c max and auc of ruxolitinib, respectively, with the administration of 10 mg single dose orally following erythromycin, a moderate cyp3a4 inhibitor, at 500 mg twice daily for 4 days, compared to receiving the oral ruxolitinib dose alone in healthy subjects. there are no clinical studies conducted with mild cyp3a4 inhibitor. cyp3a4 inducers the c max and auc of ruxolitinib decreased 32% and 61%, respectively, with the oral administration of 50 mg single dose of ruxolitinib following rifampin 600 mg once daily for 10 days, compared to receiving the oral ruxolitinib dose alone in healthy subjects. in vitro studies cytochrome p450 (cyp) enzymes: ruxolitinib is not expected to inhibit cyp1a2, 2b6, 2c8, 2c9, 2c19, 2d6 and cyp3a4 or induce cyp1a2, 2b6 and 3a4 following topical application. transporter systems: ruxolitinib is not expected to inhibit p-gp, bcrp, oatp1b1, oatp1b3, oct1, oct2, oat1, or oat3 transporter systems following topical application. ruxolitinib is not a substrate for the p-gp transporter.

tinib had no effect on fertility or reproductive function in male or female rats at doses up to 60 mg/kg/day (22 times the mrhd clinical systemic exposure). however, in female rats, doses of greater than or equal to 30 mg/kg/day (3.5 times the mrhd clinical systemic exposure) resulted in increased post-implantation loss.

tility or reproductive function in male or female rats at doses up to 60 mg/kg/day (22 times the mrhd clinical systemic exposure). however, in female rats, doses of greater than or equal to 30 mg/kg/day (3.5 times the mrhd clinical systemic exposure) resulted in increased post-implantation loss.

atment with opzelura, ruxolitinib cream, 0.75%, or vehicle cream twice daily (bid) for 8 weeks. the primary efficacy endpoint was the proportion of subjects at week 8 achieving iga treatment success (iga-ts) defined as a score of 0 (clear) or 1 (almost clear) with ≥ 2 grade improvement from baseline. efficacy was also assessed using a ≥ 4-point improvement in itch nrs. efficacy results for opzelura from the two trials are summarized in table 3. table 3: efficacy results at week 8 in subjects with atopic dermatitis (true-ad1 and true-ad2) true-ad1 true-ad2 opzelura (n = 253) vehicle (n = 126) treatment difference and 95% confidence interval opzelura (n = 228) vehicle (n = 118) treatment difference and 95% confidence interval iga-ts defined as an iga score of 0 or 1 with a ≥ 2-grade improvement from baseline 53.8% (136/253) 15.1% (19/126) 38.9% (30.3%, 47.4%) 51.3% (117/228) 7.6% (9/118) 44.1% (36.2%, 52.0%) itch nrs (≥ 4 point reduction) (n/n) n = subjects with a baseline itch nrs score ≥ 4. 52.2% (84/161) 15.4% (12/78) 36.7% (25.5%, 48.0%) 50.7% (74/146) 16.3% (13/80) 35.8% (24.4%, 47.2%) 14.2 nonsegmental vitiligo two double-blind, randomized, vehicle-controlled trials of identical design (true‑v1 and true‑v2, nct04052425 and nct04057573, respectively) enrolled a total of 674 adult and pediatric subjects aged 12 years and older (11% of subjects were 12 to 17 years of age and 7% were 65 years or older). females constituted 53% of subjects, 82% of subjects were white, 5% were black, and 4% were asian. fitzpatrick skin types included i (2%), ii (30%), iii (40%), iv (19%), v (7%), or vi (2%). subjects had depigmented areas affecting ≥ 0.5% facial body surface area (f-bsa), ≥ 3% non-facial bsa, and total body vitiligo area (facial and non-facial, including hands, feet, upper and lower extremities, and trunk body areas) of up to 10% bsa. at baseline, subjects had a mean affected f-bsa of 1% and a mean affected total bsa of 7.4%. phototherapy was not permitted during the trial. the mean time since diagnosis of nonsegmental vitiligo was 14.8 years prior to subjects enrolling in the trials. in both trials, subjects were randomized 2:1 to treatment with opzelura or vehicle cream twice daily (bid) for 24 weeks followed by an additional 28 weeks of treatment with opzelura bid for all subjects. lesions on the face were assessed with the facial vitiligo area scoring index (f-vasi) and lesions on the total body (including the face) were assessed with the total body vitiligo area scoring index (t-vasi). the primary efficacy endpoint was the proportion of subjects achieving at least 75% improvement in f-vasi (f-vasi75) at week 24. the proportion of participants achieving at least 90% improvement in f-vasi (f-vasi90) was also evaluated. efficacy results for opzelura at week 24 from the two trials are summarized in table 4. the percentage of subjects who achieved f-vasi75 and t-vasi75 (at least 75% improvement in t‑vasi) over the 52-week treatment period in both trials are shown in figure 1 and figure 2. table 4: efficacy results at week 24 in subjects with nonsegmental vitiligo (true-v1 and true-v2) true-v1 true-v2 opzelura (n = 221) vehicle (n = 109) treatment difference and 95% confidence interval opzelura (n = 229) vehicle (n = 115) treatment difference and 95% confidence interval f-vasi75 29.9% 7.5% 22.5% (14.2%, 30.8%) 29.9% 12.9% 16.9% (7.8%, 26.0%) f-vasi90 15.5% 2.2% 13.3% (7.5%, 19.1%) 15.4% 1.9% 13.5% (7.7%, 19.3%) percentage of subjects with nonsegmental vitiligo achieving f-vasi75 during the 52-week treatment period (true v1 and true v2 combined) percentage of subjects with nonsegmental vitiligo achieving t-vasi75 during the 52-week treatment period (true v1 and true v2 combined)

se patients that exposure to sunlight, and uv light should be limited by wearing protective clothing and using a broad-spectrum sunscreen [see warnings and precautions ( 5.3 )] . major adverse cardiovascular events advise patients that events of major adverse cardiovascular events (mace) including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, have been reported in clinical studies with janus kinase inhibitors used to treat inflammatory conditions. instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see warnings and precautions ( 5.4 )] . thrombosis advise patients that events of dvt and pe have been reported in clinical studies with janus kinase inhibitors used to treat inflammatory conditions. instruct patients to tell their healthcare provider if they develop any signs or symptoms of a dvt or pe [see warnings and precautions ( 5.5 )] . thrombocytopenia, anemia, and neutropenia advise patients of the risk of thrombocytopenia, anemia, and neutropenia with opzelura. instruct patients to tell their healthcare provider if they develop any signs or symptoms of thrombocytopenia, anemia, or neutropenia [see warnings and precautions ( 5.6 )] . administration instructions advise patients or caregivers that opzelura is for topical use only [see dosage and administration ( 2.1 )]. advise patients to limit treatment to one 60 gram tube per week or one 100 gram tube per 2 weeks [see dosage and administration ( 2.1 )] . pregnancy inform patients to report their pregnancy to incyte corporation at 1-855-463-3463 [see use in specific populations ( 8.1 )]. lactation advise a patient not to breastfeed during treatment with opzelura and for about four weeks after the last dose [see use in specific populations ( 8.2 )]. manufactured for: incyte corporation 1801 augustine cut-off wilmington, de 19803 opzelura is a trademark of incyte. all rights reserved. u.s. patent nos. 7598257; 8415362; 8722693; 8822481; 9079912; 9974790; 10639310; 10610530; 10758543; 10869870; 11219624 © 2021-2023 incyte corporation. all rights reserved.