observed or potential adverse reactions of jak inhibition. higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with a jak inhibitor compared to those treated with tnf blockers in rheumatoid arthritis (ra) patients. sotyktu is not approved for use in ra. (5.8) 5.1 hypersensitivity hypersensitivity reactions such as angioedema have been reported in subjects receiving sotyktu. if a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue sotyktu [see adverse reactions (6.1) ]. 5.2 infections sotyktu may increase the risk of infections. serious infections have been reported in subjects with psoriasis who received sotyktu. the most common serious infections reported with sotyktu included pneumonia and covid-19 [see adverse reactions (6.1) ] . avoid use of sotyktu in patients with an active or serious infection. consider the risks and benefits of treatment prior to initiating sotyktu in patients: • with chronic or recurrent infection • who have been exposed to tuberculosis • with a history of a serious or an opportunistic infection • 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 sotyktu. a patient who develops a new infection during treatment with sotyktu should undergo prompt and complete diagnostic testing; appropriate antimicrobial therapy should be initiated; and the patient should be closely monitored. interrupt sotyktu if a patient develops a serious infection. do not resume sotyktu until the infection resolves or is adequately treated. viral reactivation herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical trials with sotyktu. in the 16‑week placebo-controlled period, herpes simplex infections were reported in 17 subjects (6.8 per 100 patient‑years) treated with sotyktu, and 1 subject (0.8 per 100 patient-years) treated with placebo. multidermatomal herpes zoster was reported in an immunocompetent subject who received sotyktu. during pso-1, pso-2, and the open-label extension trial in which subjects who completed the controlled trials could enroll, the majority of subjects who reported events of herpes zoster while receiving sotyktu were under 50 years of age. the impact of sotyktu on chronic viral hepatitis reactivation is unknown. subjects with positive screening tests for hepatitis b or c, or chronic hepatitis b, or untreated hepatitis c were excluded from clinical trials. consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with sotyktu. if signs of reactivation occur, consult a hepatitis specialist. sotyktu is not recommended for use in patients with active hepatitis b or hepatitis c. 5.3 tuberculosis in clinical trials, of 4 subjects with latent tuberculosis (tb) who were treated with sotyktu and received appropriate tb prophylaxis, no subjects developed active tb (during the mean follow-up of 34 weeks). one subject, who did not have latent tb, developed active tb after receiving 54 weeks of sotyktu. evaluate patients for latent and active tb infection prior to initiating treatment with sotyktu. do not administer sotyktu to patients with active tb. initiate treatment of latent tb prior to administering sotyktu. consider anti-tb therapy prior to initiation of sotyktu in patients with a past history of latent or active tb in whom an adequate course of treatment cannot be confirmed. monitor patients receiving sotyktu for signs and symptoms of active tb during treatment. 5.4 malignancy including lymphomas malignancies, including lymphomas, were observed in clinical trials with sotyktu [see adverse reactions (6.1) ] . consider the benefits and risks for the individual patient prior to initiating or continuing therapy with sotyktu, particularly in patients with a known malignancy (other than a successfully treated non-melanoma skin cancer) and patients who develop a malignancy when on treatment with sotyktu. 5.5 rhabdomyolysis and elevated cpk cases of rhabdomyolysis were reported in subjects treated with sotyktu resulting in interruption or discontinuation of sotyktu dosing. treatment with sotyktu was associated with an increased incidence of asymptomatic creatine phosphokinase (cpk) elevation and rhabdomyolysis compared to treatment with placebo. discontinue sotyktu if markedly elevated cpk levels occur or myopathy is diagnosed or suspected. instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever [see adverse reactions (6.1) ]. 5.6 laboratory abnormalities triglyceride elevations - treatment with sotyktu was associated with increases in triglyceride levels. the effect of this elevated parameter on cardiovascular morbidity and mortality has not been determined. periodically evaluate serum triglycerides according to the clinical guidelines for hyperlipidemia while patients are receiving treatment with sotyktu. manage patients according to clinical guidelines for the management of hyperlipidemia [see adverse reactions (6.1) ] . liver enzyme elevations - treatment with sotyktu was associated with an increase in the incidence of liver enzyme elevation compared to treatment with placebo. liver serum transaminase elevations ≥ 3 times the uln were reported in subjects treated with sotyktu. evaluate liver enzymes at baseline and thereafter in patients with known or suspected liver disease according to routine patient management. if treatment-related increases in liver enzymes occur and drug-induced liver injury is suspected, interrupt sotyktu until a diagnosis of liver injury is excluded [see adverse reactions (6.1) ]. 5.7 immunizations prior to initiating therapy with sotyktu, consider completion of all age-appropriate immunizations according to current immunization guidelines including prophylactic herpes zoster vaccination. avoid use of live vaccines in patients treated with sotyktu. the response to live or non-live vaccines has not been evaluated. 5.8 potential risks related to jak inhibition it is not known whether tyk2 inhibition may be associated with the observed or potential adverse reactions of janus kinase (jak) inhibition. in a large, randomized, postmarketing safety trial of a jak inhibitor in rheumatoid arthritis (ra), patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with the jak inhibitor compared to those treated with tnf blockers. sotyktu is not approved for use in ra.

ded for patients with mild to moderate hepatic impairment.

ials (pso-1 and pso-2) and an open-label extension trial in which subjects who completed pso-1 or pso-2 could enroll [see clinical studies (14) ]. in these clinical trials, a total of 1,519 subjects with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy received sotyktu 6 mg orally once daily. of these, 1,141 subjects were exposed to sotyktu for at least one year. in trials pso-1 and pso-2, 1,681 subjects were randomized to receive sotyktu 6 mg (840 subjects), placebo (419 subjects), or apremilast 30 mg twice daily (422 subjects). all subjects randomized to placebo switched to sotyktu at week 16. all other subjects remained in their original treatment group until week 24, at which point subjects could have continued on the same treatment or be switched to sotyktu or placebo. the mean age of subjects was 47 years. the majority of subjects were white (87%) and male (67%). in the 16-week placebo-controlled period of the pooled clinical trials (pso-1 and pso-2), discontinuation of therapy due to adverse reactions in subjects who received sotyktu was 2.4%, compared to 3.8% for placebo. table 1 summarizes the adverse reactions that occurred in at least 1% of subjects in the sotyktu group and at a higher rate than the placebo group during the 16-week controlled period. table 1: adverse reactions that occurred in ≥ 1% of subjects with plaque psoriasis in the sotyktu group and more frequently than in the placebo group in trials pso-1 and pso-2 through week 16 a includes upper respiratory tract infection (viral, bacterial, and unspecified), nasopharyngitis, pharyngitis (including viral, streptococcal, and unspecified), sinusitis (includes acute, viral, bacterial), rhinitis, rhinotracheitis, tracheitis, laryngitis, and tonsillitis (including bacterial, streptococcal) b includes oral herpes, genital herpes, herpes simplex, and herpes virus infection c includes mouth ulceration, aphthous ulcer, tongue ulceration, and stomatitis d includes acne, acne cystic, and dermatitis acneiform adverse reaction sotyktu 6 mg once daily placebo n=840 n (%) n=419 n (%) upper respiratory infections a 161 (19.2) 62 (14.8) blood creatine phosphokinase increased 23 (2.7) 5 (1.2) herpes simplex b 17 (2.0) 1 (0.2) mouth ulcers c 16 (1.9) 0 (0.0) folliculitis 14 (1.7) 0 (0.0) acne d 12 (1.4) 1 (0.2) adverse reactions that occurred in < 1% of subjects in the sotyktu group were herpes zoster. specific adverse reactions exposure adjusted incidence rates are reported for all the adverse reactions presented below. infections in the 16-week placebo-controlled period, infections occurred in 29% of the sotyktu group (116 events per 100 person-years) compared to 22% of the placebo group (83.7 events per 100 person-years). the majority of infections were non-serious and mild to moderate in severity and did not lead to discontinuation of sotyktu. in the 16-week placebo-controlled period, serious infections were reported in 5 subjects (2.0 per 100 patient-years) treated with sotyktu, and 2 subjects (1.6 per 100 patient-years) treated with placebo. the most common serious infections reported during the 52-week treatment period were pneumonia and covid-19. malignancies during the 0-to-52-week treatment period of the two clinical trials, pso-1 and pso-2 (total exposure of 986 patient-years with sotyktu), malignancies (excluding non-melanoma skin cancer) were reported in 3 subjects treated with sotyktu (0.3 per 100 patient-years), including single cases each of breast cancer, hepatocellular carcinoma, and lymphoma after 24, 32, and 25 weeks of treatment, respectively. during pso-1, pso-2, and the open-label extension trial in which subjects who completed the controlled trials could enroll, a total of 3 subjects (0.1 per 100 patient-years), developed lymphoma while receiving sotyktu after 25, 77, and 98 weeks of treatment. laboratory abnormalities creatine phosphokinase (cpk) in the 16-week placebo-controlled period, increased cpk (including grade 4) was reported in 23 subjects (9.3 per 100 patient-years) treated with sotyktu, and 5 subjects (4.1 per 100 patient-years) treated with placebo. liver enzyme elevations events of increases in liver enzymes ≥3 times the uln were observed in subjects treated with sotyktu [see warnings and precautions (5.5) ] . in the 16-week placebo-controlled period: • alt elevations ≥3 times the uln was reported in 9 subjects (3.6 per 100 patient- years) treated with sotyktu, and 2 subjects (1.6 per 100 patient-years) treated with placebo. • ast elevations ≥3 times the uln was reported in 13 subjects (5.2 per 100 patient- years) treated with sotyktu, and 2 subjects (1.6 per 100 patient-years) treated with placebo. decreased glomerular filtration rate (gfr) in the 16-week placebo-controlled period in subjects who had moderate renal impairment (egfr 30-59 ml/min) at baseline, decreased gfr was reported in 4 subjects (1.6 per 100 patient-years) treated with sotyktu, and 1 subject (0.8 per 100 patient-years) treated with placebo. two of the deucravacitinib-treated subjects had worsening of baseline proteinuria. lipid elevations mean triglycerides increased by 10.3 mg/dl during the 16-week treatment period in subjects treated with sotyktu and by 9.1 mg/dl during the 52-week treatment period. safety through week 52 in pso-1 and pso-2, the exposure adjusted incidence rate of adverse reactions in subjects treated with sotyktu from week 0 through week 52 without switching treatment did not increase compared to the rate observed during the first 16 weeks of treatment.

pregnancies to the bristol-myers squibb company’s adverse event reporting line at 1-800-721-5072. data animal data deucravacitinib was administered orally during the period of organogenesis at doses of 5, 15, or 75 mg/kg/day in rats and 1, 3, or 10 mg/kg/day in rabbits. deucravacitinib was not associated with embryo-fetal lethality or fetal malformations in either species. these doses resulted in maternal exposures (auc) that were 266 times (rat) or 91 times (rabbit) the exposure at the mrhd. in a pre- and post-natal development study in rats, deucravacitinib was administered orally from gestation day 6 through lactation day 20, at doses of 5, 15, or 50 mg/kg/day. at 50 mg/kg/day, f1 offspring had reduced body weight gains during the pre-weaning period. after weaning, body weights of affected f1 offspring gradually normalized to control levels. no maternal effects were observed at 50 mg/kg/day (110 times the mrhd based on auc comparison). no deucravacitinib-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring were noted at doses up to 15 mg/kg/day (19 times the mrhd based on auc comparison). 8.2 lactation risk summary there are no data on the presence of deucravacitinib in human milk, the effects on the breastfed infant, or the effects on milk production. deucravacitinib is present in rat milk. when a drug is present in animal milk, it is likely that the drug will be present in human milk (see data ). the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sotyktu and any potential adverse effects on the breastfed infant from sotyktu or from the underlying maternal condition. data animal data a single oral dose of 5 mg/kg radiolabeled deucravacitinib was administered to lactating (post-partum days 8 to 12) rats. deucravacitinib and/or its metabolites were present in the milk of lactating rats. 8.4 pediatric use the safety and effectiveness of sotyktu in pediatric patients have not been established. 8.5 geriatric use of the 1,519 subjects with plaque psoriasis treated with sotyktu, 152 (10%) subjects were 65 years or older and 21 (1.4%) subjects were 75 years or older. during the week 0-16 period, for those subjects (80 subjects ≥ 65 years old, including 12 subjects ≥ 75 years old) who received sotyktu without switching treatment arms, there was a higher rate of overall serious adverse reactions, including serious infections, and discontinuations due to adverse reactions compared with younger adults. no overall differences in effectiveness of sotyktu have been observed between patients 65 years of age and older and younger adult patients. 8.6 renal impairment no dose adjustment of sotyktu is recommended in patients with mild, moderate, or severe renal impairment or in patients with end stage renal disease (esrd) on dialysis [see clinical pharmacology (12.3) ] . 8.7 hepatic impairment no dose adjustment of sotyktu is recommended in patients with mild (child-pugh a) or moderate (child-pugh b) hepatic impairment. sotyktu is not recommended for use in patients with severe hepatic impairment (child-pugh c) [see adverse reactions (6.1) and clinical pharmacology (12.3) ] .

ucravacitinib was administered orally during the period of organogenesis at doses of 5, 15, or 75 mg/kg/day in rats and 1, 3, or 10 mg/kg/day in rabbits. deucravacitinib was not associated with embryo-fetal lethality or fetal malformations in either species. these doses resulted in maternal exposures (auc) that were 266 times (rat) or 91 times (rabbit) the exposure at the mrhd. in a pre- and post-natal development study in rats, deucravacitinib was administered orally from gestation day 6 through lactation day 20, at doses of 5, 15, or 50 mg/kg/day. at 50 mg/kg/day, f1 offspring had reduced body weight gains during the pre-weaning period. after weaning, body weights of affected f1 offspring gradually normalized to control levels. no maternal effects were observed at 50 mg/kg/day (110 times the mrhd based on auc comparison). no deucravacitinib-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring were noted at doses up to 15 mg/kg/day (19 times the mrhd based on auc comparison).

uced psoriasis-associated gene expression in psoriatic skin in a dose dependent manner, including reductions in il-23-pathway and type i ifn pathway regulated genes. deucravacitinib reduced il-17a, il-19 and beta-defensin by 47 to 50%, 72%, and 81 to 84% respectively following 16 weeks of once daily treatment. the relationship between these pharmacodynamic markers and the mechanism(s) by which deucravacitinib exerts its clinical effects is unknown. cardiac electrophysiology at a dose 6 times the recommended dose of the 6 mg once daily in psoriasis patients, sotyktu does not prolong the qtc interval to any clinically relevant extent. 12.3 pharmacokinetics following oral administration, deucravacitinib plasma c max and auc increased proportionally over a dose range from 3 mg to 36 mg (0.5 to 6 times the approved recommended dosage) in healthy subjects. the accumulation of deucravacitinib was <1.4-fold following once daily dosing in healthy subjects. the pk of deucravacitinib and its active metabolite, bmt‑153261, were comparable between healthy subjects and subjects with psoriasis. the steady state c max and auc 24 of deucravacitinib following administration of 6 mg once daily were 45 ng/ml and 473 ng·hr/ml, respectively. the steady state c max and auc 24 of the active deucravacitinib metabolite, bmt-153261, following administration of 6 mg once daily were 5 ng/ml and 95 ng·hr/ml, respectively. absorption the absolute oral bioavailability of deucravacitinib was 99% and the median t max ranged from 2 to 3 hours in healthy subjects. food effect no clinically significant differences in the pharmacokinetics of deucravacitinib were observed following administration of a high-fat, high-calorie meal (951 kcal in total, with approximate distribution of 52% fat, 33% carbohydrate and 15% protein). c max and auc of deucravacitinib when administered with food were decreased by approximately 24% and 11%, respectively, and t max was prolonged by 1 hour. c max and auc of bmt-153261 when administered with food were decreased by approximately 23% and 10%, respectively, and t max was prolonged by 2 hours. distribution the volume of distribution of deucravacitinib at steady state is 140 l. protein binding of deucravacitinib was 82 to 90% and the blood-to-plasma concentration ratio was 1.26. elimination the terminal half-life of deucravacitinib was 10 hours. the renal clearance of deucravacitinib ranged from 27 to 54 ml/minute. metabolism deucravacitinib is metabolized by cytochrome p-450 (cyp) 1a2 to form major metabolite bmt-153261. deucravacitinib is also metabolized by cyp2b6, cyp2d6, carboxylesterase (ces) 2, and uridine glucuronyl transferase (ugt) 1a9. the active deucravacitinib metabolite, bmt-153261, has comparable potency to the parent drug, but the circulating exposure of bmt-153261 accounts for approximately 20% of the systemic exposure of the total drug-related components. excretion after a single dose of radiolabeled deucravacitinib, approximately 13% and 26% of the dose was recovered as unchanged in urine and feces, respectively. approximately 6% and 12% of the dose was detected as bmt-153261 in urine and feces, respectively. specific populations patients with renal impairment deucravacitinib c max was 14% lower and 6% higher in patients with mild (egfr ≥60 to <90 ml/min/1.73m 2 ) and moderate (egfr ≥30 to <60 ml/min/1.73m 2 ) renal impairment, compared to subjects with normal renal function (egfr ≥ 90 ml/min/1.73m 2 ); no change in c max was observed in patients with severe (egfr <30 ml/min/1.73m 2 ) renal impairment, and esrd (egfr <15 ml/min/1.73m 2 ) on dialysis. deucravacitinib auc inf was unchanged in patients with mild renal impairment but higher by 39%, 28% and 34% in patients with moderate, severe and esrd on dialysis, respectively, compared to subjects with normal renal function. bmt-153261 c max was 11% lower, 8% lower, 28% higher and 9% higher in patients with mild, moderate, severe renal impairment and esrd on dialysis, respectively, compared to subjects with normal renal function. bmt-153261 auc inf was 2% lower, 24% higher, 81% higher and 27% higher in patients with mild, moderate, severe renal impairment and esrd on dialysis, respectively, compared to subjects with normal renal function. dialysis did not substantially clear deucravacitinib from systemic circulation (5.4% of dose cleared per dialysis). patients with hepatic impairment deucravacitinib c max was higher by 4%, 10% and 1% in patients with mild (child-pugh class a), moderate (child-pugh class b), and severe (child-pugh class c) hepatic impairment, respectively, compared to subjects with normal hepatic function. deucravacitinib auc inf was higher by 10%, 40% and 43% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function. bmt-153261 c max was lower by 25%, 59% and 79% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function. bmt-153261 auc inf was lower by 3%, 20% and 50% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function [see use in specific populations (8.7) ] . body weight, gender, race, and age body weight, gender, race, and age did not have a clinically meaningful effect on deucravacitinib exposure. drug interaction studies clinical trials no clinically significant differences in the pharmacokinetics of deucravacitinib were observed when co-administered with the following drugs: cyclosporine (dual pgp/bcrp inhibitor), fluvoxamine (cyp1a2 inhibitor), ritonavir (cyp1a2 inducer), diflunisal (ugt 1a9 inhibitor), pyrimethamine (oct1 inhibitor), famotidine (h2 receptor antagonist), or rabeprazole (proton pump inhibitor). no clinically significant differences in the pharmacokinetics of the following drugs were observed when co-administered with deucravacitinib: rosuvastatin, methotrexate, mycophenolate mofetil (mmf) and oral contraceptives (norethindrone acetate and ethinyl estradiol). in vitro studies cytochrome p450 (cyp) enzymes: deucravacitinib is not an inhibitor of cyp1a2, cyp2b6, cyp2c8, cyp2c9, cyp2c19, cyp2d6, or cyp3a4. deucravacitinib is not an inducer of cyp1a2, cyp2b6, or cyp3a4. carboxylesterase (ces) enzymes: deucravacitinib is not an inhibitor of ces2. uridine diphosphate (udp)-glucuronosyl transferase (ugt) enzymes: deucravacitinib is not an inhibitor of ugt1a1, ugt1a4, ugt1a6, ugt1a9, or ugt2b7. transporter systems: deucravacitinib is a substrate of pgp, bcrp, and oct1, but not oatp, ntcp, oat1, oat3, oct2, mate1, or mate2k. deucravacitinib is an inhibitor of bcrp and oatp1b3, but not an inhibitor of pgp, oatp1b1, ntcp, bsep, mrp2, oat1, oat3, oct1, oct2, mate1, or mate2-k.

f deucravacitinib were observed following administration of a high-fat, high-calorie meal (951 kcal in total, with approximate distribution of 52% fat, 33% carbohydrate and 15% protein). c max and auc of deucravacitinib when administered with food were decreased by approximately 24% and 11%, respectively, and t max was prolonged by 1 hour. c max and auc of bmt-153261 when administered with food were decreased by approximately 23% and 10%, respectively, and t max was prolonged by 2 hours. distribution the volume of distribution of deucravacitinib at steady state is 140 l. protein binding of deucravacitinib was 82 to 90% and the blood-to-plasma concentration ratio was 1.26. elimination the terminal half-life of deucravacitinib was 10 hours. the renal clearance of deucravacitinib ranged from 27 to 54 ml/minute. metabolism deucravacitinib is metabolized by cytochrome p-450 (cyp) 1a2 to form major metabolite bmt-153261. deucravacitinib is also metabolized by cyp2b6, cyp2d6, carboxylesterase (ces) 2, and uridine glucuronyl transferase (ugt) 1a9. the active deucravacitinib metabolite, bmt-153261, has comparable potency to the parent drug, but the circulating exposure of bmt-153261 accounts for approximately 20% of the systemic exposure of the total drug-related components. excretion after a single dose of radiolabeled deucravacitinib, approximately 13% and 26% of the dose was recovered as unchanged in urine and feces, respectively. approximately 6% and 12% of the dose was detected as bmt-153261 in urine and feces, respectively. specific populations patients with renal impairment deucravacitinib c max was 14% lower and 6% higher in patients with mild (egfr ≥60 to <90 ml/min/1.73m 2 ) and moderate (egfr ≥30 to <60 ml/min/1.73m 2 ) renal impairment, compared to subjects with normal renal function (egfr ≥ 90 ml/min/1.73m 2 ); no change in c max was observed in patients with severe (egfr <30 ml/min/1.73m 2 ) renal impairment, and esrd (egfr <15 ml/min/1.73m 2 ) on dialysis. deucravacitinib auc inf was unchanged in patients with mild renal impairment but higher by 39%, 28% and 34% in patients with moderate, severe and esrd on dialysis, respectively, compared to subjects with normal renal function. bmt-153261 c max was 11% lower, 8% lower, 28% higher and 9% higher in patients with mild, moderate, severe renal impairment and esrd on dialysis, respectively, compared to subjects with normal renal function. bmt-153261 auc inf was 2% lower, 24% higher, 81% higher and 27% higher in patients with mild, moderate, severe renal impairment and esrd on dialysis, respectively, compared to subjects with normal renal function. dialysis did not substantially clear deucravacitinib from systemic circulation (5.4% of dose cleared per dialysis). patients with hepatic impairment deucravacitinib c max was higher by 4%, 10% and 1% in patients with mild (child-pugh class a), moderate (child-pugh class b), and severe (child-pugh class c) hepatic impairment, respectively, compared to subjects with normal hepatic function. deucravacitinib auc inf was higher by 10%, 40% and 43% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function. bmt-153261 c max was lower by 25%, 59% and 79% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function. bmt-153261 auc inf was lower by 3%, 20% and 50% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function [see use in specific populations (8.7) ] . body weight, gender, race, and age body weight, gender, race, and age did not have a clinically meaningful effect on deucravacitinib exposure. drug interaction studies clinical trials no clinically significant differences in the pharmacokinetics of deucravacitinib were observed when co-administered with the following drugs: cyclosporine (dual pgp/bcrp inhibitor), fluvoxamine (cyp1a2 inhibitor), ritonavir (cyp1a2 inducer), diflunisal (ugt 1a9 inhibitor), pyrimethamine (oct1 inhibitor), famotidine (h2 receptor antagonist), or rabeprazole (proton pump inhibitor). no clinically significant differences in the pharmacokinetics of the following drugs were observed when co-administered with deucravacitinib: rosuvastatin, methotrexate, mycophenolate mofetil (mmf) and oral contraceptives (norethindrone acetate and ethinyl estradiol). in vitro studies cytochrome p450 (cyp) enzymes: deucravacitinib is not an inhibitor of cyp1a2, cyp2b6, cyp2c8, cyp2c9, cyp2c19, cyp2d6, or cyp3a4. deucravacitinib is not an inducer of cyp1a2, cyp2b6, or cyp3a4. carboxylesterase (ces) enzymes: deucravacitinib is not an inhibitor of ces2. uridine diphosphate (udp)-glucuronosyl transferase (ugt) enzymes: deucravacitinib is not an inhibitor of ugt1a1, ugt1a4, ugt1a6, ugt1a9, or ugt2b7. transporter systems: deucravacitinib is a substrate of pgp, bcrp, and oct1, but not oatp, ntcp, oat1, oat3, oct2, mate1, or mate2k. deucravacitinib is an inhibitor of bcrp and oatp1b3, but not an inhibitor of pgp, oatp1b1, ntcp, bsep, mrp2, oat1, oat3, oct1, oct2, mate1, or mate2-k.

le rats, deucravacitinib had no effects on mating, fertility, or early embryonic parameters at oral doses up to 50 mg/kg/day (171 times the mrhd based on auc comparison).

ad no effects on mating, fertility, or early embryonic parameters at oral doses up to 50 mg/kg/day (171 times the mrhd based on auc comparison).

ment from baseline; • the proportion of subjects who achieved at least a 75% improvement in pasi scores from baseline (pasi 75). other comparisons between sotyktu and placebo that were secondary endpoints at week 16: • the proportion of subjects who achieved pasi 90, pasi 100, spga 0, scalp severity pga (ss-pga) score of 0 (clear) or 1 (almost clear) with at least 2-grade improvement, and psoriasis symptoms and signs diary (pssd) symptom score of 0 (symptom-free). comparisons between sotyktu and apremilast were made for the following secondary endpoints at these time points: • at week 16 and week 24 (pso-1 and pso-2), the proportion of subjects who achieved pasi 75, pasi 90, and spga 0/1 with at least a 2-grade improvement from baseline • at week 16 (pso-1 and pso-2), the proportion of subjects who achieved spga 0 and ss-pga 0/1 with at least a 2-grade improvement from baseline (scalp). results in both trials, the mean age was 47 years, the mean weight was 91 kg, 67% of subjects were male, 13% were hispanic or latino, 87% were white, 2% were black, and 10% were asian. at baseline, subjects had a median affected bsa of 20% and a median pasi score of 19. the proportion of subjects with spga score of 3 (moderate) and 4 (severe) at baseline were 80% and 20%, respectively. approximately 18% of subjects had a history of psoriatic arthritis. across both trials, 40% of subjects had received prior phototherapy, 42% were naive to any systemic therapy (including biologic and/or non-biologic treatment), 41% received prior non-biologic systemic treatment, and 35% had received prior biologic therapy. table 2 presents the efficacy results of sotyktu compared to apremilast and placebo in pso-1. table 3 presents the efficacy results in pso-2. table 2: efficacy results in adults with moderate to severe plaque psoriasis (nri a ) in pso-1 ci = confidence interval; pasi = psoriasis area and severity index; spga = static physician global assessment; ss-pga = scalp specific physician’s global assessment a nri = non-responder imputation b adjusted difference in proportions is the weighted average of the treatment differences across region, body weight and prior biologic use with the cochran-mantel-haenszel weights. c co-primary endpoints comparing sotyktu to placebo d includes only subjects with baseline ss-pga score of ≥ 3 endpoint sotyktu (n=330) n (%) placebo (n=166) n (%) apremilast (n=168) n (%) difference, % (95% ci) b difference from placebo difference from apremilast spga response of 0/1 (clear or almost clear) week 16 c 178 (54) 12 (7) 54 (32) 47 (40, 53) 22 (13, 30) week 24 194 (59) - 52 (31) - 27 (19, 36) spga response of 0 week 16 58 (18) 1 (1) 8 (5) 17 (13, 21) 13 (8, 18) pasi 75 response week 16 c 193 (58) 21 (13) 59 (35) 46 (39, 53) 23 (14, 32) week 24 228(69) - 64 (38) - 31 (22, 40) pasi 90 response week 16 118 (36) 7 (4) 33 (20) 32 (26, 38) 16 (8, 24) week 24 140 (42) - 37 (22) - 20 (12, 28) pasi 100 response week 16 47 (14) 1 (1) - 14 (10, 18) - ss-pga response of 0/1 (scalp) d (n=209) (n=121) (n=110) week 16 147 (70) 21 (17) 43 (39) 53 (44, 62) 30 (19, 41) table 3: efficacy results in adults with moderate to severe plaque psoriasis (nri a ) in pso-2 ci = confidence interval; pasi = psoriasis area and severity index; spga = static physician global assessment; ss-pga = scalp specific physician’s global assessment a nri = non-responder imputation b adjusted difference in proportions is the weighted average of the treatment differences across region, body weight and prior biologic use with the cochran-mantel-haenszel weights. c co-primary endpoints comparing sotyktu to placebo d includes only subjects with baseline ss-pga score of ≥ 3 endpoint sotyktu (n=511) n (%) placebo (n=255) n (%) apremilast (n=254) n (%) difference, % (95% ci) b difference from placebo difference from apremilast spga response of 0/1 (clear or almost clear) week 16 c 253 (50) 22 (9) 86 (34) 41 (35, 46) 16 (9, 23) week 24 251 (49) - 75 (30) - 20 (13, 27) spga response of 0 week 16 80 (16) 3 (1) 16 (6) 14 (11, 18) 9 (5, 14) pasi 75 response week 16 c 271 (53) 24 (9) 101 (40) 44 (38, 49) 13 (6, 21) week 24 296 (58) - 96 (38) - 20 (13, 27) pasi 90 response week 16 138 (27) 7 (3) 46 (18) 24 (20, 29) 9 (3, 15) week 24 164 (32) - 50 (20) - 13 (6, 19) pasi 100 response week 16 52 (10%) 3 (1) - 9 (6, 12) - ss-pga response of 0/1 (scalp) d (n=305) (n=173) (n=166) week 16 182 (60) 30 (17) 61 (37) 42 (34, 50) 23 (14, 33) examination of age, gender, race, body weight, baseline disease severity, and prior systemic therapy did not identify differences in response to sotyktu at week 16 among these subgroups. maintenance and durability of response in pso-1, among subjects who received sotyktu and had spga 0/1 response at week 24, the spga 0/1 response at week 52 was 78% (151/194). among subjects who received sotyktu and had pasi 75 response at week 24, the pasi 75 response at week 52 was 82% (187/228). among subjects who received sotyktu and had pasi 90 response at week 24, the pasi 90 response at week 52 was 74% (103/140). in pso-2, to evaluate maintenance and durability of response, subjects who were originally randomized to sotyktu and were pasi 75 responders at week 24, were re-randomized to either continue treatment on sotyktu or be withdrawn from therapy (i.e., receive placebo). for subjects who were re-randomized and also had a spga score of 0 or 1 at week 24, 70% (83/118) of subjects who continued on sotyktu maintained this response (spga 0 or 1) at week 52 compared to 24% (28/119) of subjects who were re-randomized to placebo. in addition, at week 52, 80% (119/148) of subjects who continued on sotyktu maintained pasi 75 compared to 31% (47/150) of subjects who were withdrawn from sotyktu. for spga 0 or 1 responders at week 24 who were re-randomized to treatment withdrawal (i.e., placebo), the median time to loss of spga score of 0 or 1 was approximately 8 weeks. for pasi 75 responders at week 24 who were re-randomized to treatment withdrawal (i.e., placebo), the median time to loss of pasi 75 was approximately 12 weeks. patient reported outcomes a greater proportion of subjects treated with sotyktu compared to placebo achieved psoriasis symptoms and signs diary (pssd) symptom score of 0 (absence of itch, pain, burning, stinging, and skin tightness) at week 16 (8% in sotyktu vs. 1% in placebo) in both trials.

ancies including lymphomas. instruct patients to inform their healthcare provider if they have ever had any type of cancer [see warnings and precautions (5.4) ] . rhabdomyolysis inform patients that sotyktu may increase their risk of developing rhabdomyolysis. instruct patients to immediately inform their healthcare provider if they develop unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever [see warnings and precautions (5.5) ]. laboratory abnormalities inform patients that sotyktu may affect certain lab tests, and that blood tests may be required before and during sotyktu treatment [see warnings and precautions (5.6) ] . immunizations advise patients that vaccination with live vaccines is not recommended during sotyktu treatment. medications that interact with the immune system may increase the risk of infection following administration of live vaccines. instruct patients to inform the healthcare practitioner that they are taking sotyktu prior to a potential vaccination [see warnings and precautions (5.7) ] . pregnancy advise patients to report their pregnancy to bristol-myers squibb company at 1-800-721-5072 [see use in specific populations (8.1 )].