Get your patient on Sotyktu (Deucravacitinib)

SOTYKTU is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Limitations of Use :

SOTYKTU is not recommended for use in combination with other potent immunosuppressants.

SOTYKTU is indicated for the treatment of active psoriatic arthritis in adults.

Evaluate patients for active and latent tuberculosis (TB) infection prior to initiating treatment with SOTYKTU. Do not administer SOTYKTU to patients with active TB. Start treatment for latent TB prior to initiation of SOTYKTU use [see Warnings and Precautions (5.3) ].

Complete all immunizations according to current immunization guidelines [see Warnings and Precautions (5.7) ] .

The recommended dosage of SOTYKTU is 6 mg taken orally once daily, with or without food.

Do not crush, cut, or chew the tablets.

SOTYKTU is not recommended in patients with severe hepatic impairment (Child-Pugh C) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ].

No dosage adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

The safety and effectiveness of SOTYKTU in pediatric patients have not been established.

Plaque Psoriasis

In clinical trials of SOTYKTU in adults with moderate to severe plaque psoriasis, of the 1,519 subjects, 152 (10%) subjects were 65 years or older and 21 (1.4%) subjects were 75 years or older.

During the Week 0-16 period of the clinical trials 80 subjects ≥ 65 years old, including 12 subjects ≥ 75 years old, who received SOTYKTU without switching treatment arms, had a higher incidence of overall serious adverse reactions, including serious infections, and discontinuations due to adverse reactions compared with younger adult subjects.

No overall differences in effectiveness of SOTYKTU have been observed between patients 65 years of age and older and younger adult patients.

Psoriatic Arthritis

In clinical trials of SOTYKTU in adults with active psoriatric arthritis, of the 1312 subjects treated with SOTYKTU, 171 (13%) patients were 65 years or older and 22 (1.7%) subjects were 75 years or older. No overall differences safety or effectiveness of SOTYKTU or exposure of deucravacitinib were observed between subjects 65 years of age and older and younger adult subjects.

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) ] .

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) ] .

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 Contraindications (4) ].

SOTYKTU may increase the risk of infections.

Serious infections have been reported in subjects 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 SOTYKTU prior to initiating treatment 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. Patients who develops a new infection during treatment with SOTYKTU should undergo prompt and complete diagnostic testing, have appropriate antimicrobial therapy be initiated, and be closely monitored. Interrupt SOTYKTU if a serious infection occurs. 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 [see Adverse Reactions (6.1) ] . In the 16‑week placebo-controlled period of Trials PSO-1 and PSO-2, 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.

The clinical implications of SOTYKTU on viral hepatitis reactivation are unknown. Subjects with positive screening tests for hepatitis B or C, or chronic hepatitis B, or untreated hepatitis C were excluded from clinical trials or closely monitored for evidence of reactivation. 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.

In Trials PSO-1 and PSO-2, 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.

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 during treatment with SOTYKTU.

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) ].

Triglyceride Elevations - Treatment with SOTYKTU was associated with increases in triglyceride levels [see Adverse Reactions (6.1) ] . 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.

Liver Enzyme Elevations - Treatment with SOTYKTU has been associated with liver enzyme elevation. Liver serum transaminase elevations ≥3 times the ULN have been reported in subjects treated with SOTYKTU [see Adverse Reactions (6.1) ]. Evaluate liver enzymes at baseline and during treatment SOTYKTU in patients with known or suspected liver disease according to routine patient management. If increases in liver enzymes occur and drug-induced liver injury is suspected, interrupt SOTYKTU until a diagnosis of liver injury is excluded.

Prior to initiating therapy with SOTYKTU, complete 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.

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.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Plaque Psoriasis Clinical Trials

The safety of SOTYKTU was evaluated in two placebo- and active-controlled trials (Trial PSO-1 and Trial PSO-2) and an open-label extension trial in which subjects who completed Trial PSO-1 or Trial PSO-2 could enroll [see Clinical Studies (14.1) ]. 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 once daily (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 (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.

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.

Deucravacitinib is an inhibitor of tyrosine kinase 2 (TYK2). TYK2 is a member of the Janus kinase (JAK) family. Deucravacitinib binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction between the regulatory and the catalytic domains of the enzyme. This results in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream activation of Signal Transducers and Activators of Transcription (STATs) as shown in cell-based assays. JAK kinases, including TYK2, function as pairs of homo- or heterodimers in the JAK-STAT pathways. TYK2 pairs with JAK1 to mediate multiple cytokine pathways and also pairs with JAK2 to transmit signals as shown in cell-based assays. The precise mechanism linking inhibition of TYK2 enzyme to treatment of moderate-to-severe plaque psoriasis or active psoriatric arthritis is not currently known.

In patients with moderate to severe plaque psoriasis, deucravacitinib reduced 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. In patients with moderate to severe plaque psoriasis and active psoriatic arthritis, deucravacitinib reduced circulating IL-17A, IL-19 and beta-defensin following 16 weeks of once daily treatment. In patients with active psoriatic arthritis, reduction in biomarkers including C-reactive protein (CRP), matrix metalloproteinase-3 (MMP3), matrix metalloproteinase-1 (MMP1), type I collagen degradation product (C1M) and TNF-alpha was also observed. The relationship between these pharmacodynamic markers and the mechanism(s) by which deucravacitinib exerts its clinical effects is unknown.

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 pharmacokinetics of deucravacitinib and its active metabolite, BMT‑153261, were comparable between healthy subjects and subjects with plaque 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, in subjects with plaque psoriasis, and 53 ng/mL and 598 ng·hr/mL respectively, in subjects with psoriasis arthritis.

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, in subjects with plaque psoriasis subjects and 19 ng/mL and 209 ng·hr/mL respectively, in subjects with psoriasis arthritis subjects.

The carcinogenic potential of deucravacitinib was assessed in 2-year rat and 6-month rasH2 transgenic mouse studies. No evidence of tumorigenicity was observed in male or female rats that received deucravacitinib at oral doses up to 15 mg/kg/day (41 times the MRHD based on AUC comparison). No evidence of tumorigenicity was observed in male or female Tg.rasH2 mice that received deucravacitinib at oral doses up to 60 mg/kg/day.

Deucravacitinib was not mutagenic in a bacterial mutagenicity assay (Ames test) or clastogenic in an in vitro chromosomal aberration assay (cultured Chinese hamster ovary cells) or in an in vivo rat peripheral blood micronucleus assay.

In male rats, deucravacitinib had no effects on reproductive parameters (mating, fertility, and sperm morphology) or early embryonic development of their offspring at oral doses up to 50 mg/kg/day (178 times the MRHD based on AUC comparison).

In female rats, deucravacitinib had no effects on mating, fertility, or early embryonic parameters at oral doses up to 50 mg/kg/day (136 times the MRHD based on AUC comparison).

The efficacy and safety of SOTYKTU were assessed in two multicenter, randomized, double-blind, placebo- and active-controlled clinical trials, Trial PSO-1 (NCT03624127) and Trial PSO-2 (NCT03611751) which enrolled subjects 18 years of age and older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Subjects had a body surface area (BSA) involvement of ≥ 10%, a Psoriasis Area and Severity Index (PASI) score ≥ 12, and a static Physician’s Global Assessment (sPGA) ≥ 3 (moderate or severe).

In Trials PSO-1 and PSO-2, efficacy was assessed in 1,684 subjects randomized to either SOTYKTU (6 mg orally once daily), placebo, or apremilast (30 mg orally twice daily).

The efficacy and safety of SOTYKTU were assessed in two multicenter randomized, double-blind, placebo-controlled trials (Trial PsA-1, [NCT04908202] and Trial PsA-2, [NCT04908189]) in subjects 18 years and older with active psoriatic arthritis (PsA) (≥3 swollen joints, ≥3 tender joints, a C-reactive protein (CRP) level of ≥3 mg/L) and with active or a history of plaque psoriasis. Subjects in both trials at baseline had a diagnosis of psoriatic arthritis for at least 3 months and met the Classification criteria for Psoriatic Arthritis (CASPAR) at screening. In Trial PsA-1, subjects also had presence of at least one bone erosion on X-ray of hands and/or feet. Trial PsA-2 included an active safety reference treatment arm (apremilast).

The efficacy of SOTYKTU was assessed in 1,294 subjects up to Week 16. Trial PsA-1 evaluated 670 subjects who were randomized to placebo or SOTYKTU 6 mg once daily. Trial PsA-2 evaluated 624 subjects who were randomized to placebo or SOTYKTU 6 mg once daily. In addition, 105 subjects were randomized to apremilast 30 mg twice daily in Trial PsA-2. In both trials, subjects randomized to placebo were switched to SOTYKTU at Week 16.

Baseline Characteristics

Across the two trials, the mean age was 51 years, the mean weight was 84 kg, 49% of subjects were male, 23% were Hispanic or Latino, 78% were White, and 0.4% were Black and 11% were Asian. In the two trials, subjects had a median duration of disease of 4.0 years and the majority of subjects had polyarthritis (76%) followed by oligoarthritis (14%). 8% of subjects had predominant distal interphalangeal joint involvement, while 16% had peripheral plus psoriatic spondylarthritis. Dactylitis and enthesitis were present in 31% and 49% of subjects respectively. 49% had psoriasis skin involvement that was ≥3% body surface area (BSA) and a Static Physician’s Global Assessment (sPGA) of at least 2.

In the two trials, the majority of subjects were naïve to biologic treatment and had experienced an inadequate response, intolerance or loss of response to nonsteroidal anti-inflammatory drugs (NSAIDs), conventional synthetic DMARDs (csDMARDs), or apremilast. In addition, Trial PsA-2 included anti-TNF alpha-experienced subjects. In the two trials, 56% of subjects were taking concomitant methotrexate (MTX). 10% were taking other concomitant csDMARDs, and 34% were not taking csDMARDs.

Endpoints and Results

The primary endpoint in both trials were the percentage of subjects who achieved an American College of Rheumatology (ACR) 20 response at Week 16.

ACR Response

In both trials, treatment with SOTYKTU resulted in statistically significant improvement in disease activity, as measured by ACR 20, compared to placebo at Week 16 (see Table 4). Improvement in disease activity was also demonstrated as measured by ACR 50/70 compared with placebo at Week 16. In both trials, ACR20 responses at Week 16 were consistent regardless of concomitant DMARD use, age, gender, race, or baseline disease characteristics in patients receiving SOTYKTU. In Trial PsA-2, similar ACR response rates were seen regardless of prior anti-TNF alpha therapy.

Improvements in ACR 20 and individual ACR components from baseline were observed in subjects treated with SOTYKTU at Week 16. The percentage of subjects achieving ACR20 responses in Trial PsA-1 by visit through Week 16 is shown in Figure 1. Similar responses were seen in Trial PsA-2 up to Week 16. Results of the components of the ACR response criteria for both trials are shown in Table 5.

Figure 1: Percent of Subjects Achieving ACR20 Responses in Trial PsA-1 through Week 16

In subjects with coexistent plaque psoriasis receiving SOTYKTU, statistically significant improvement was observed, relative to placebo, as measured by the Psoriasis Area Severity Index (PASI 75) at Week 16.

Physical Function Response

In both trials, subjects treated with SOTYKTU showed a statistically significant improvement from baseline in physical function as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) compared with placebo. The adjusted mean difference (95% CI) from placebo in HAQ-DI change from baseline at Week 16 was -0.17 (-0.24, -0.09) in Trial PsA-1 and -0.11 (-0.18, -0.04) in Trial PsA-2. The proportion of HAQ-DI responders (≥ 0.35 improvement from baseline) at Week 16 in Trial PsA-1 was 51% in the SOTYKTU group and 39% in the placebo group and in Trial PsA-2 was 49% in the SOTYKTU group and 43% in the placebo group.

Other Health-Related Outcomes

Health-related quality of life was assessed by the SF-36. Subjects treated with SOTYKTU showed improvements in SF-36 Physical Component Summary (PCS) score at Week 16 compared to placebo. There were also improvements in all four SF-36 (PCS) domain scale scores: physical functioning, role-physical, bodily-pain, and general health.