Skyrizi

— THERAPEUTIC CATEGORIES —
  • Arthritis/rheumatic disorders
  • Colorectal disorders
  • Psoriasis
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Skyrizi Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Risankizumab-rzaa 75mg/0.83mL, 150mg/mL; soln for SC inj; 60mg/mL; soln for IV infusion after dilution; preservative-free.

    Pharmacological Class

    Interleukin-23 antagonist.

    How Supplied

    Single-dose prefilled syringe (75mg/0.83mL)—2 (w. supplies); Single-dose prefilled pen or syringe (150mg/mL)—1 (w. supplies); Single-dose prefilled cartridge (180mg/1.2mL, 360mg/2.4mL)—1 (kit w. on-body injector); Single-dose vial (600mg/10mL)—1

    How Supplied

    Subcutaneous Injection 

    Skyrizi 150 mg/mL prefilled syringe or prefilled pen contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe or prefilled pen consists of a 1 mL glass syringe with a fixed 27-gauge ½ inch needle with needle guard. Pack size - carton of 1.

    Skyrizi 75 mg/0.83 mL prefilled syringe is a sterile, preservative-free, colorless to slightly yellow and clear to slightly opalescent solution. Each prefilled syringe consists of a 1 mL glass syringe with a fixed 29-gauge ½ inch needle with needle guard. Pack size - carton of 2.

    Skyrizi 180 mg/1.2 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with a septum and cap contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Pack size - Kit.

    Skyrizi 360 mg/2.4 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with a septum and cap contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Pack size - Kit.

     

    Intravenous Infusion

    Skyrizi 600 mg/10 mL (60 mg/mL) vial contains a sterile and preservative-free, colorless to slightly yellow, and clear to slightly opalescent solution. Each glass vial is closed with a stopper and blue flip cap. Pack size - carton of 1.

    Storage

    Store in a refrigerator at 36°F to 46° F (2°C to 8°C). Do not freeze. Do not shake. Keep in the original cartons to protect from light. Not made with natural rubber latex. 

    Storage of Diluted Solution: If not used immediately, store the diluted Skyrizi solution refrigerated and protected from light for up to 20 hours between 36°F to 46°F (2°C to 8°C). Subsequently, the diluted Skyrizi solution can be stored (protected from direct and indirect sunlight) for 8 hours at room temperature at up to 77°F (25°C) after dilution (cumulative time after preparation including the storage and the infusion period). Do not freeze. 

    Manufacturer

    AbbVie

    Generic Availability

    NO

    Skyrizi Indications

    Indications

    Active psoriatic arthritis.

    Skyrizi Dosage and Administration

    Prior to Treatment Evaluations

    For the treatment of Crohn’s disease, obtain liver enzymes and bilirubin levels prior to initiating treatment with Skyrizi.

    Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Skyrizi.

    Complete all age-appropriate vaccinations as recommended by current immunization guidelines.

    Adult

    Administer by SC inj into abdomen, thighs (or may be given by healthcare provider only in upper, outer arm). ≥18yrs: 150mg by SC inj at Week 0, Week 4, and every 12 weeks thereafter. May be given alone or in combination with non-biologic DMARDs.

    Children

    <18yrs: not established.

    Skyrizi Contraindications

    Not Applicable

    Skyrizi Boxed Warnings

    Not Applicable

    Skyrizi Warnings/Precautions

    Warnings/Precautions

    Use under physician supervision and guidance. Discontinue if serious hypersensitivity reactions (eg, anaphylaxis) occur; treat appropriately. Increased risk of infections. Active infection: do not initiate until resolves or treated. Chronic or history of recurrent infection: consider risks/benefits. Evaluate for tuberculosis (TB) infection prior to initiation. History of latent or active TB (without confirmed adequate treatment); consider anti-TB therapy prior to initiating. Monitor for active TB during and after therapy. Patients with active TB infection: do not initiate. Complete all immunizations according to current guidelines prior to initiation. For Crohn disease: obtain liver enzymes, bilirubin levels prior to initiation and during induction at least up to 12 weeks of treatment. Interrupt therapy if drug-induced liver injury is suspected. Consider alternative treatment in those with evidence of liver cirrhosis. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity Reactions 

    • Discontinue and initiate appropriate therapy immediately if serious hypersensitivity reactions, including anaphylaxis, occur.

    Infections

    • May increase the risk of infections.

    • Do not initiate treatment in patients with any clinically important active infection until the infection resolves or is adequately treated.

    • Prior to prescribing Skyrizi, consider the risks and benefits in patients with a chronic infection or a history of recurrent infection. Seek medical advice if signs or symptoms of clinically important infection occur. 

    • Monitor closely and do not administer Skyrizi if a patient develops an infection or is not responding to standard therapy until the infection resolves. 

    Tuberculosis

    • Evaluate for tuberculosis (TB) infection prior to initiating treatment with Skyrizi.

    • Consider anti-TB therapy prior to initiating Skyrizi in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. 

    • Monitor for signs and symptoms of active TB during and after Skyrizi treatment. Do not administer Skyrizi to patients with active TB.

    Hepatotoxicity in Treatment of Crohn’s Disease

    • For the treatment of Crohn’s disease, evaluate liver enzymes and bilirubin at baseline, and during induction at least up to 12 weeks of treatment. Monitor thereafter according to routine patient management.

    • Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.

    Administration of Vaccines

    • Avoid use of live vaccines in patients treated with Skyrizi. 

    • Prior to initiating therapy with Skyrizi, complete all age-appropriate vaccinations according to current immunization guidelines.

    Pregnancy Considerations

    Pregnancy Exposure Registry

    • There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while treated with Skyrizi. Patients should be encouraged to enroll by calling 1-877-302-2161 or visiting http://glowpregnancyregistry.com.

    Risk Summary

    • Available pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. 

    • Although there are no data on risankizumab-rzaa, monoclonal antibodies can be actively transported across the placenta, and Skyrizi may cause immunosuppression in the in utero-exposed infant. There are adverse pregnancy outcomes in women with inflammatory bowel disease.

    Clinical Considerations

    • Disease-associated maternal and embryo/fetal risk: Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

    • Fetal/Neonatal adverse reactions: Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Because risankizumab may interfere with immune response to infections, consider the risks and benefits prior to administering live vaccines to infants exposed to Skyrizi in utero. Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, a minimum of 5 months after birth should be considered because of the half-life of the product.

    Nursing Mother Considerations

    Risk Summary

    • There are no data on the presence of risankizumab-rzaa in human milk, the effects on the breastfed infant, or the effects on milk production.

    • The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Skyrizi and any potential adverse effects on the breastfed infant from Skyrizi or from the underlying maternal condition.

    Pediatric Considerations

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

    Geriatric Considerations

    Plaque psoriasis: No overall differences in Skyrizi exposure, safety, or effectiveness were observed between older and younger subjects who received Skyrizi. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects. 

    Crohn disease: Clinical studies of Skyrizi for the treatment of Crohn’s disease did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects. No clinically meaningful differences in the pharmacokinetics of risankizumab-rzaa were observed in geriatric subjects compared to younger adult subjects with Crohn’s disease.

    Skyrizi Pharmacokinetics

    Absorption

    The absolute bioavailability of risankizumab-rzaa was estimated to be 74 to 89% following subcutaneous injection. In healthy subjects, following administration of a single subcutaneous dose, Cmax was reached by 3 to 14 days.

    Distribution

    The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis, and 7.68 L (64%) in subjects with Crohn’s disease. 

    Metabolism

    The metabolic pathway of risankizumab-rzaa has not been characterized. As a humanized IgG1 monoclonal antibody, risankizumab-rzaa is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.

    Elimination

    The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) and 0.30 L/day (34%) and terminal elimination half-life was approximately 28 days and 21 days in subjects with plaque psoriasis and Crohn’s disease, respectively.

    Skyrizi Interactions

    Interactions

    Avoid use of live vaccines.

    Skyrizi Adverse Reactions

    Adverse Reactions

    Upper respiratory infections, headache, fatigue, inj site reactions, tinea infections; hypersensitivity reactions.

    Skyrizi Clinical Trials

    Clinical Trials

    Psoriatic Arthritis (PsA)

    The safety and efficacy of Skyrizi were evaluated in 1407 subjects in 2 randomized, double-blind, placebo-controlled studies (964 in PsA-1 [NCT03675308] and 443 in PsA-2 [NCT03671148]) in patients 18 years and older with active psoriatic arthritis (PsA).

    Patients in these studies had a diagnosis of PsA for at least 6 months based on the Classification Criteria for Psoriatic Arthritis (CASPAR), a median duration of PsA of 4.9 years at baseline, ≥ 5 tender joints and ≥ 5 swollen joints, and active plaque psoriasis or psoriatic nail disease at baseline.

    In PsA-1, all subjects had a previous inadequate response or intolerance to non-biologic DMARD therapy and were biologic naïve. In PsA-2, 53.5% of subjects had a previous inadequate response or intolerance to non-biologic DMARD therapy, and 46.5% of subjects had a previous inadequate response or intolerance to biologic therapy. In both studies, subjects were randomly assigned to receive Skyrizi 150 mg or placebo at Weeks 0, 4, and 16. Starting from Week 28, all subjects received Skyrizi every 12 weeks. Both studies included a long-term extension for up to an additional 204 weeks. Regarding use of concomitant medications, 59.6% of subjects were receiving concomitant methotrexate (MTX), 11.6% were receiving concomitant non-biologic DMARDs other than MTX, and 28.9% were receiving SKYRIZI monotherapy. 

    For both studies, the primary endpoint was the proportion of subjects who achieved an American College of Rheumatology (ACR) 20 response at Week 24.

    In Study PsA-1, treatment with Skyrizi achieved the following improvements in ACR responses compared with placebo, respectively:

    • ACR20 Response 

      • Week 16: 56.3% vs 33.4% (treatment difference, 23.1%; 95% CI, 16.8-29.4; multiplicity-controlled P ≤.001)

      • Week 24: 57.3% vs 33.5% (treatment difference, 24.0%; 95% CI, 18-30; multiplicity-controlled P ≤.001)

    • ACR50 Response

      • Week 16: 26.4% vs 11.1% (treatment difference, 15.4%; 95% CI, 10.6-20.2)

      • Week 24: 33.4% vs 11.3% (treatment difference, 22.2%; 95% CI, 17.3-27.2)

    • ACR70 Response 

      • Week 16: 11.8% vs 2.7% (treatment difference, 9.2%; 95% CI, 6.1-12.4)

      • Week 24: 15.3% vs 4.7% (treatment difference, 10.5%; 95% CI, 6.9-14.2)

    In Study PsA-2, treatment with Skyrizi achieved the following improvements in ACR responses compared with placebo, respectively:

    • ACR20 Response 

      • Week 16: 48.3% vs 25.3% (treatment difference, 22.6%; 95% CI, 13.9-31.2; multiplicity-controlled P ≤.001)

      • Week 24: 51.3% vs 26.5% (treatment difference, 24.5%; 95% CI, 15.9-33.0; multiplicity-controlled P ≤.001)

    • ACR50 Response 

      • Week 16: 20.3% vs 6.8% (treatment difference, 13.5%; 95% CI, 7.3-19.7)

      • Week 24: 26.3% vs 9.3% (treatment difference, 16.6%; 95% CI, 9.7-23.6)

    • ACR70 Response 

      • Week 16: 11.2% vs 3.4% (treatment difference, 7.8%; 95% CI, 3.0-12.6)

      • Week 24: 12.0% vs 5.9% (treatment difference, 6.0%; 95% CI, 0.8-11.3)

    In Studies PsA-1 and PsA-2, treatment with Skyrizi had a mean change from baseline in ACR components compared with placebo, respectively:

    • Number of Swollen Joints (0-66)

      • Week 16: -7.7 and -8.0 vs -5.5 and -5.4

      • Week 24: -8.7 and -9.1 vs -6.7 and -6.5

    • Number of Tender Joints (0-68)

      • Week 16: -10.7 and -11.3 vs -6.3 and -6.0

      • Week 24: -12.0 and -13.0 vs -7.9 and -8.3

    • Patient’s Assessment of Pain

      • Week 16: -18.4 and -14.4 vs -8.6 and -5.7

      • Week 24: -21.4 and -15.3 vs -10.9 and -8.7

    • Patient’s Global Assessment 

      • Week 16: -19.4 and -17.0 vs -10.2 and -4.9

    • Physician’s Global Assessment 

      • Week 16: -31.1 and -32.7 vs -18.3 and -19.0

      • Week 24: -34.8 and -35.5 vs -22.2 and -21.3

    • Health Assessment Questionnaire - Disability Index (HAQ-DI)

      • Week 16: -0.3 and -0.2 vs -0.1 and -0.1

      • Week 24: -0.3 and -0.2 vs -0.1 and -0.1

    • High sensitivity C-reactive protein (hs-CRP) mg/L 

      • Week 16: -4.8 and -2.1 vs -0.3 and -0.1

      • Week 24: -4.3 and -1.8 vs -0.2 and -0.5

    Treatment with Skyrizi resulted in improvement in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis. In patients with coexistent plaque psoriasis receiving Skyrizi, the skin lesions of psoriasis improved with treatment, relative to placebo, as measured by the Psoriasis Area Severity Index (PASI 90) at Week 24.

    Physical Function: In both studies, patients treated with Skyrizi showed statistically significant improvement from baseline in physical function compared with placebo as assessed by HAQ-DI at Week 24. The mean difference (95% CI) from placebo in HAQ-DI change from baseline at Week 24 was -0.20 (-0.26, -0.14) in study PsA-1 and -0.16 (-0.26, -0.07) in study PsA-2.

    In both studies, a greater proportion of subjects achieved a reduction of at least 0.35 in HAQ-DI score from baseline in the Skyrizi group compared with placebo at Week 24.

    Other Health Related Outcomes: In both studies, general health status was assessed by the 36-Item Short Form Health Survey (SF36 V2). Fatigue was assessed by Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue).

    In both studies at Week 24, patients treated with Skyrizi showed improvements in the SF-36 physical component summary scores compared with subjects who received placebo. There were also numerical improvements in patients treated with Skyrizi in physical functioning, role physical, bodily pain, general health, vitality, social functioning, mental health, role emotional domain scores and mental component summary scores in both studies at week 24 compared to placebo. In both studies at Week 24, patients treated with Skyrizi showed improvements in FACIT-Fatigue scores compared with subjects who received placebo.

    For more trial data: see full labeling.

    Skyrizi Note

    Not Applicable

    Skyrizi Patient Counseling

    Cost Savings Program

    Skyrizi Patient Support & Resources: https://www.skyrizi.com/skyrizi-complete/save-on-skyrizi-costs

    Skyrizi Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Risankizumab-rzaa 75mg/0.83mL, 150mg/mL; soln for SC inj; 60mg/mL; soln for IV infusion after dilution; preservative-free.

    Pharmacological Class

    Interleukin-23 antagonist.

    How Supplied

    Single-dose prefilled syringe (75mg/0.83mL)—2 (w. supplies); Single-dose prefilled pen or syringe (150mg/mL)—1 (w. supplies); Single-dose prefilled cartridge (180mg/1.2mL, 360mg/2.4mL)—1 (kit w. on-body injector); Single-dose vial (600mg/10mL)—1

    How Supplied

    Subcutaneous Injection 

    Skyrizi 150 mg/mL prefilled syringe or prefilled pen contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe or prefilled pen consists of a 1 mL glass syringe with a fixed 27-gauge ½ inch needle with needle guard. Pack size - carton of 1.

    Skyrizi 75 mg/0.83 mL prefilled syringe is a sterile, preservative-free, colorless to slightly yellow and clear to slightly opalescent solution. Each prefilled syringe consists of a 1 mL glass syringe with a fixed 29-gauge ½ inch needle with needle guard. Pack size - carton of 2.

    Skyrizi 180 mg/1.2 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with a septum and cap contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Pack size - Kit.

    Skyrizi 360 mg/2.4 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with a septum and cap contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Pack size - Kit.

     

    Intravenous Infusion

    Skyrizi 600 mg/10 mL (60 mg/mL) vial contains a sterile and preservative-free, colorless to slightly yellow, and clear to slightly opalescent solution. Each glass vial is closed with a stopper and blue flip cap. Pack size - carton of 1.

    Storage

    Store in a refrigerator at 36°F to 46° F (2°C to 8°C). Do not freeze. Do not shake. Keep in the original cartons to protect from light. Not made with natural rubber latex. 

    Storage of Diluted Solution: If not used immediately, store the diluted Skyrizi solution refrigerated and protected from light for up to 20 hours between 36°F to 46°F (2°C to 8°C). Subsequently, the diluted Skyrizi solution can be stored (protected from direct and indirect sunlight) for 8 hours at room temperature at up to 77°F (25°C) after dilution (cumulative time after preparation including the storage and the infusion period). Do not freeze. 

    Manufacturer

    AbbVie

    Generic Availability

    NO

    Skyrizi Indications

    Indications

    Moderately to severely active Crohn disease.

    Skyrizi Dosage and Administration

    Prior to Treatment Evaluations

    For the treatment of Crohn’s disease, obtain liver enzymes and bilirubin levels prior to initiating treatment with Skyrizi.

    Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Skyrizi.

    Complete all age-appropriate vaccinations as recommended by current immunization guidelines.

    Adult

    ≥18yrs: Induction: 600mg administered by IV infusion over at least 1hr at Week 0, Week 4, and Week 8. Complete infusion within 8hrs of dilution. Maintenance: 180mg or 360mg administered by SC inj into thigh or abdomen (using the on-body injector) at Week 12, and every 8 weeks thereafter. Use the lowest effective dosage needed to maintain therapeutic response.

     

    Children

    <18yrs: not established.

    Skyrizi Contraindications

    Not Applicable

    Skyrizi Boxed Warnings

    Not Applicable

    Skyrizi Warnings/Precautions

    Warnings/Precautions

    Use under physician supervision and guidance. Discontinue if serious hypersensitivity reactions (eg, anaphylaxis) occur; treat appropriately. Increased risk of infections. Active infection: do not initiate until resolves or treated. Chronic or history of recurrent infection: consider risks/benefits. Evaluate for tuberculosis (TB) infection prior to initiation. History of latent or active TB (without confirmed adequate treatment); consider anti-TB therapy prior to initiating. Monitor for active TB during and after therapy. Patients with active TB infection: do not initiate. Complete all immunizations according to current guidelines prior to initiation. For Crohn disease: obtain liver enzymes, bilirubin levels prior to initiation and during induction at least up to 12 weeks of treatment. Interrupt therapy if drug-induced liver injury is suspected. Consider alternative treatment in those with evidence of liver cirrhosis. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity Reactions 

    • Serious hypersensitivity reactions, including anaphylaxis, have been reported with use of Skyrizi. If a serious hypersensitivity reaction occurs, discontinue Skyrizi and initiate appropriate therapy immediately.

    Infections

    • Skyrizi may increase the risk of infections.

    • Treatment with Skyrizi should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

    • In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing Skyrizi. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. 

    • If a patient develops such an infection or is not responding to standard therapy, monitor the patient closely and do not administer Skyrizi until the infection resolves. 

    Tuberculosis

    • Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Skyrizi.

    • Consider anti-TB therapy prior to initiating Skyrizi in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. 

    • Monitor patients for signs and symptoms of active TB during and after Skyrizi treatment. Do not administer Skyrizi to patients with active TB.

    Hepatotoxicity in Treatment of Crohn’s Disease

    • For the treatment of Crohn’s disease, evaluate liver enzymes and bilirubin at baseline, and during induction at least up to 12 weeks of treatment. Monitor thereafter according to routine patient management.

    • Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.

    Administration of Vaccines

    • Avoid use of live vaccines in patients treated with Skyrizi. 

    • Prior to initiating therapy with Skyrizi, complete all age-appropriate vaccinations according to current immunization guidelines.

    Pregnancy Considerations

    Pregnancy Exposure Registry

    • There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while treated with Skyrizi. Patients should be encouraged to enroll by calling 1-877-302-2161 or visiting http://glowpregnancyregistry.com.

    Risk Summary

    • Available pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. 

    • Although there are no data on risankizumab-rzaa, monoclonal antibodies can be actively transported across the placenta, and Skyrizi may cause immunosuppression in the in utero-exposed infant. There are adverse pregnancy outcomes in women with inflammatory bowel disease.

    Clinical Considerations

    • Disease-associated maternal and embryo/fetal risk: Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

    • Fetal/Neonatal adverse reactions: Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Because risankizumab may interfere with immune response to infections, risks and benefits should be considered prior to administering live vaccines to infants exposed to Skyrizi in utero. There are insufficient data regarding infant serum levels of risankizumab at birth and the duration of persistence of risankizumab in infant serum after birth. Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, a minimum of 5 months after birth should be considered because of the half-life of the product.

    Nursing Mother Considerations

    Risk Summary

    • There are no data on the presence of risankizumab-rzaa in human milk, the effects on the breastfed infant, or the effects on milk production.

    • The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Skyrizi and any potential adverse effects on the breastfed infant from Skyrizi or from the underlying maternal condition.

    Pediatric Considerations

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

    Geriatric Considerations

    Plaque psoriasis: Of the 2234 subjects with plaque psoriasis exposed to Skyrizi, 243 subjects were 65 years or older and 24 subjects were 75 years or older. No overall differences in Skyrizi exposure, safety, or effectiveness were observed between older and younger subjects who received Skyrizi. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects. 

    Crohn disease: Clinical studies of Skyrizi for the treatment of Crohn’s disease did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects. No clinically meaningful differences in the pharmacokinetics of risankizumab-rzaa were observed in geriatric subjects compared to younger adult subjects with Crohn’s disease.

    Skyrizi Pharmacokinetics

    Absorption

    The absolute bioavailability of risankizumab-rzaa was estimated to be 74 to 89% following subcutaneous injection. In healthy subjects, following administration of a single subcutaneous dose, Cmax was reached by 3 to 14 days.

    Distribution

    The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis, and 7.68 L (64%) in subjects with Crohn’s disease. 

    Metabolism

    The metabolic pathway of risankizumab-rzaa has not been characterized. As a humanized IgG1 monoclonal antibody, risankizumab-rzaa is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.

    Elimination

    The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) and 0.30 L/day (34%) and terminal elimination half-life was approximately 28 days and 21 days in subjects with plaque psoriasis and Crohn’s disease, respectively.

    Skyrizi Interactions

    Interactions

    Avoid use of live vaccines.

    Skyrizi Adverse Reactions

    Adverse Reactions

    Upper respiratory infections, headache, arthralgia, inj site reactions, abdominal pain, anemia, pyrexia, back pain, arthropathy, urinary tract infection; hypersensitivity reactions, hepatotoxicity.

    Skyrizi Clinical Trials

    Clinical Trials

    Crohn’s Disease

    Induction Trials (Studies CD-1 and CD-2)

    In two 12-week induction studies (CD-1; NCT03105128 and CD-2; NCT03104413), patients with moderately to severely active Crohn’s disease were randomly assigned to receive Skyrizi 600 mg, Skyrizi 1,200 mg, or placebo as an intravenous infusion at Week 0, Week 4, and Week 8. Moderately to severely active CD was defined as a Crohn’s Disease Activity Index (CDAI) of 220 to 450 and Simple Endoscopic Score for Crohn’s disease (SES-CD) ≥6 (or ≥4 for isolated ileal disease). Subjects with inadequate response, loss of response, or intolerance to oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapy were enrolled.

    The coprimary endpoints for both studies were clinical remission and endoscopic response at Week 12. Secondary endpoints included clinical response and endoscopic remission. The Skyrizi 1,200 mg dosage did not demonstrate additional treatment benefit over the 600 mg dosage and is not a recommended regimen.

    In Study CD-1, a greater proportion of patients treated with Skyrizi 600 mg achieved the following efficacy endpoints at week 12 compared with placebo, respectively:

    • Clinical remission: 45% vs 25% (treatment difference 21%; 95% CI, 12-29; P <.001)

    • Endoscopic response: 40% vs 12% (treatment difference 28%; 95% CI, 21-35; P <.001)

    • Clinical response: 60% vs 37% (treatment difference 23%; 95% CI, 14-32; P <.001)

    • Endoscopic remission: 24% vs 9% (treatment difference 15%; 95% CI, 9-21; P <.001)

    In Study CD-2, a greater proportion of patients treated with Skyrizi 600 mg achieved the following efficacy endpoints at week 12 compared with placebo, respectively:

    • Clinical remission: 42% vs 20% (treatment difference 22%; 95% CI, 13-31; P <.001)

    • Endoscopic response: 29% vs 11% (treatment difference 18%; 95% CI, 10-25; P <.001)

    • Clinical response: 60% vs 30% (treatment difference 29%; 95% CI, 20-39; P <.001)

    • Endoscopic remission: 19% vs 4% (treatment difference 15%; 95% CI, 9-21; P <.001)

    Onset of clinical response and clinical remission based on CDAI occurred as early as Week 4 in a greater proportion of patients treated with the Skyrizi 600 mg induction regimen compared to placebo.

    Reductions in stool frequency and abdominal pain were observed in a greater proportion of patients treated with the Skyrizi 600 mg induction regimen compared to placebo. 

    For more trial data: see full labeling.

     

    Study CD-3

    The maintenance study CD-3 evaluated 382 patients who achieved clinical response defined as a reduction in CDAI of at least 100 points from baseline after 12 weeks of induction treatment with intravenous Skyrizi in studies CD-1 and CD-2. Patients were randomly assigned to receive a maintenance regimen of Skyrizi 180 mg or Skyrizi 360 mg or placebo at Week 12 and every 8 weeks thereafter for up to an additional 52 weeks. The co-primary endpoints in CD-3 were clinical remission and endoscopic response at Week 52.

    Results showed that treatment with Skyrizi 180mg and 360mg achieved the following efficacy endpoints at week 52 compared with placebo, respectively:

    • Clinical remission: 61% (treatment difference, 17%; 95% CI, 6-28; P <.05) and 57% (treatment difference, 14%; 95% CI, 3-26; P <.05) vs 46%

    • Endoscopic response: 50% (treatment difference, 30%; 95% CI, 20-39; P <.05) and 48% (treatment difference, 31%; 95% CI, 21-41; P <.05) vs 22%

    Endoscopic remission was observed at Week 52 in 33% (44/135) of patients treated with the Skyrizi 180 mg maintenance regimen and 41% (48/117) of patients treated with the Skyrizi 360 mg maintenance regimen, compared to 13% (17/130) of patients treated with placebo. This endpoint was not statistically significant under the prespecified multiple testing procedure.

    Skyrizi Note

    Not Applicable

    Skyrizi Patient Counseling

    Patient Counseling

    Hypersensitivity Reactions 

    Advise patients to discontinue Skyrizi and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.

    Infections

    Inform patients that Skyrizi may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection.

    Hepatotoxicity in Treatment of Crohn’s Disease 

    Inform patients that Skyrizi may cause liver injury, especially during the initial 12 weeks of treatment. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of liver dysfunction. (e.g., unexplained rash, nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine).

    Administration of Vaccines

    Advise patients that vaccination with live vaccines is not recommended during Skyrizi treatment and immediately prior to or after Skyrizi 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 Skyrizi prior to a potential vaccination. 

    Administration Instruction 

    Instruct patients or caregivers to perform the first self-injected dose under the supervision and guidance of a qualified healthcare professional for training in preparation and administration of Skyrizi, including choosing anatomical sites for administration, and proper subcutaneous injection technique.

    If using Skyrizi 75 mg/0.83 mL, instruct patients or caregivers to administer two 75 mg single-dose syringes to achieve the full 150 mg dose of Skyrizi.

    Instruct patients or caregivers in the technique of pen or syringe disposal.

    Pregnancy

    Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to Skyrizi during pregnancy.

    Cost Savings Program

    Skyrizi Patient Support & Resources: https://www.skyrizi.com/skyrizi-complete/save-on-skyrizi-costs

    Skyrizi Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Risankizumab-rzaa 75mg/0.83mL, 150mg/mL; soln for SC inj; 60mg/mL; soln for IV infusion after dilution; preservative-free.

    Pharmacological Class

    Interleukin-23 antagonist.

    How Supplied

    Single-dose prefilled syringe (75mg/0.83mL)—2 (w. supplies); Single-dose prefilled pen or syringe (150mg/mL)—1 (w. supplies); Single-dose prefilled cartridge (180mg/1.2mL, 360mg/2.4mL)—1 (kit w. on-body injector); Single-dose vial (600mg/10mL)—1

    How Supplied

    Subcutaneous Injection 

    Skyrizi 150 mg/mL prefilled syringe or prefilled pen contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution. Each prefilled syringe or prefilled pen consists of a 1 mL glass syringe with a fixed 27-gauge ½ inch needle with needle guard. Pack size - carton of 1.

    Skyrizi 75 mg/0.83 mL prefilled syringe is a sterile, preservative-free, colorless to slightly yellow and clear to slightly opalescent solution. Each prefilled syringe consists of a 1 mL glass syringe with a fixed 29-gauge ½ inch needle with needle guard. Pack size - carton of 2.

    Skyrizi 180 mg/1.2 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with a septum and cap contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Pack size - Kit.

    Skyrizi 360 mg/2.4 mL (150 mg/mL) cyclic olefin polymer prefilled cartridge with a septum and cap contains a sterile, preservative-free, colorless to yellow, and clear to slightly opalescent solution for use with supplied on-body injector administration device. Pack size - Kit.

     

    Intravenous Infusion

    Skyrizi 600 mg/10 mL (60 mg/mL) vial contains a sterile and preservative-free, colorless to slightly yellow, and clear to slightly opalescent solution. Each glass vial is closed with a stopper and blue flip cap. Pack size - carton of 1.

    Storage

    Store in a refrigerator at 36°F to 46° F (2°C to 8°C). Do not freeze. Do not shake. Keep in the original cartons to protect from light. Not made with natural rubber latex. 

    Storage of Diluted Solution: If not used immediately, store the diluted Skyrizi solution refrigerated and protected from light for up to 20 hours between 36°F to 46°F (2°C to 8°C). Subsequently, the diluted Skyrizi solution can be stored (protected from direct and indirect sunlight) for 8 hours at room temperature at up to 77°F (25°C) after dilution (cumulative time after preparation including the storage and the infusion period). Do not freeze. 

    Manufacturer

    AbbVie

    Generic Availability

    NO

    Skyrizi Indications

    Indications

    Moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

    Skyrizi Dosage and Administration

    Prior to Treatment Evaluations

    For the treatment of Crohn’s disease, obtain liver enzymes and bilirubin levels prior to initiating treatment with Skyrizi.

    Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Skyrizi.

    Complete all age-appropriate vaccinations as recommended by current immunization guidelines.

    Adult

    Administer by SC inj into abdomen, thighs (or may be given by healthcare provider only in upper, outer arm). ≥18yrs: 150mg by SC inj at Week 0, Week 4, and every 12 weeks thereafter.

    Children

    <18yrs: not established.

    Skyrizi Contraindications

    Not Applicable

    Skyrizi Boxed Warnings

    Not Applicable

    Skyrizi Warnings/Precautions

    Warnings/Precautions

    Use under physician supervision and guidance. Discontinue if serious hypersensitivity reactions (eg, anaphylaxis) occur; treat appropriately. Increased risk of infections. Active infection: do not initiate until resolves or treated. Chronic or history of recurrent infection: consider risks/benefits. Evaluate for tuberculosis (TB) infection prior to initiation. History of latent or active TB (without confirmed adequate treatment); consider anti-TB therapy prior to initiating. Monitor for active TB during and after therapy. Patients with active TB infection: do not initiate. Complete all immunizations according to current guidelines prior to initiation. For Crohn disease: obtain liver enzymes, bilirubin levels prior to initiation and during induction at least up to 12 weeks of treatment. Interrupt therapy if drug-induced liver injury is suspected. Consider alternative treatment in those with evidence of liver cirrhosis. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity Reactions 

    • Discontinue and initiate appropriate therapy immediately if serious hypersensitivity reactions, including anaphylaxis, occur.

    Infections

    • May increase the risk of infections.

    • Do not initiate treatment in patients with any clinically important active infection until the infection resolves or is adequately treated.

    • Prior to prescribing Skyrizi, consider the risks and benefits in patients with a chronic infection or a history of recurrent infection. Seek medical advice if signs or symptoms of clinically important infection occur. 

    • Monitor closely and do not administer Skyrizi if a patient develops an infection or is not responding to standard therapy until the infection resolves. 

    Tuberculosis

    • Evaluate for tuberculosis (TB) infection prior to initiating treatment with Skyrizi.

    • Consider anti-TB therapy prior to initiating Skyrizi in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. 

    • Monitor for signs and symptoms of active TB during and after Skyrizi treatment. Do not administer Skyrizi to patients with active TB.

    Hepatotoxicity in Treatment of Crohn’s Disease

    • For the treatment of Crohn’s disease, evaluate liver enzymes and bilirubin at baseline, and during induction at least up to 12 weeks of treatment. Monitor thereafter according to routine patient management.

    • Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.

    Administration of Vaccines

    • Avoid use of live vaccines in patients treated with Skyrizi. 

    • Prior to initiating therapy with Skyrizi, complete all age-appropriate vaccinations according to current immunization guidelines.

    Pregnancy Considerations

    Pregnancy Exposure Registry

    • There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while treated with Skyrizi. Patients should be encouraged to enroll by calling 1-877-302-2161 or visiting http://glowpregnancyregistry.com.

    Risk Summary

    • Available pharmacovigilance and clinical trial data with risankizumab use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. 

    • Although there are no data on risankizumab-rzaa, monoclonal antibodies can be actively transported across the placenta, and Skyrizi may cause immunosuppression in the in utero-exposed infant. There are adverse pregnancy outcomes in women with inflammatory bowel disease.

    Clinical Considerations

    • Disease-associated maternal and embryo/fetal risk: Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

    • Fetal/Neonatal adverse reactions: Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester. Because risankizumab may interfere with immune response to infections, consider the risks and benefits prior to administering live vaccines to infants exposed to Skyrizi in utero. Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, a minimum of 5 months after birth should be considered because of the half-life of the product.

    Nursing Mother Considerations

    Risk Summary

    • There are no data on the presence of risankizumab-rzaa in human milk, the effects on the breastfed infant, or the effects on milk production.

    • The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Skyrizi and any potential adverse effects on the breastfed infant from Skyrizi or from the underlying maternal condition.

    Pediatric Considerations

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

    Geriatric Considerations

    Plaque psoriasis: No overall differences in Skyrizi exposure, safety, or effectiveness were observed between older and younger subjects who received Skyrizi. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects. 

    Crohn disease: Clinical studies of Skyrizi for the treatment of Crohn’s disease did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects. No clinically meaningful differences in the pharmacokinetics of risankizumab-rzaa were observed in geriatric subjects compared to younger adult subjects with Crohn’s disease.

    Skyrizi Pharmacokinetics

    Absorption

    The absolute bioavailability of risankizumab-rzaa was estimated to be 74 to 89% following subcutaneous injection. In healthy subjects, following administration of a single subcutaneous dose, Cmax was reached by 3 to 14 days.

    Distribution

    The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis, and 7.68 L (64%) in subjects with Crohn’s disease. 

    Metabolism

    The metabolic pathway of risankizumab-rzaa has not been characterized. As a humanized IgG1 monoclonal antibody, risankizumab-rzaa is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.

    Elimination

    The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) and 0.30 L/day (34%) and terminal elimination half-life was approximately 28 days and 21 days in subjects with plaque psoriasis and Crohn’s disease, respectively.

    Skyrizi Interactions

    Interactions

    Avoid use of live vaccines.

    Skyrizi Adverse Reactions

    Adverse Reactions

    Upper respiratory infections, headache, fatigue, inj site reactions, tinea infections; hypersensitivity reactions.

    Skyrizi Clinical Trials

    Clinical Trials

    Plaque Psoriasis

    Four multicenter, randomized, double-blind studies [PsO-1 (NCT02684370), PsO-2 (NCT02684357), PsO-3 (NCT02672852), and PsO-4 (NCT02694523)] enrolled 2109 patients 18 years of age and older with moderate to severe plaque psoriasis who had a body surface area (BSA) involvement of ≥10%, a static Physician’s Global Assessment (sPGA) score of ≥3 (“moderate”) in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on a severity scale of 0 to 4, and a Psoriasis Area and Severity Index (PASI) score ≥12.

    Studies PsO-1 and PsO-2: 997 patients were randomly assigned to receive either Skyrizi 150mg (n=598), placebo (n=200), or a biologic active control (n=199) at weeks 0, 4, and every 12 weeks thereafter. The coprimary endpoints were the proportion of patients who achieved an sPGA score of 0 “clear” or 1 “almost clear” and the proportion of patients who achieved at least a 90% reduction from baseline PASI (PASI 90) at week 16. Secondary endpoints included the proportion of patients who achieved PASI 100, sPGA 0, and Psoriasis Symptom Scale (PSS) 0 at week 16.

    In the PsO-1 study, a greater proportion of patients in the Skyrizi treatment arm achieved the primary and secondary endpoints at week 16 vs those in the placebo arm, respectively:

    • sPGA 0 or 1: 88% vs 8%

    • PASI 90: 75% vs 5%

    • sPGA 0: 37% vs 2%

    • PASI 100: 36% vs 0%

    In the PsO-2 study, a greater proportion of patients in the Skyrizi treatment arm achieved the primary and secondary endpoints at week 16 vs those in the placebo arm, respectively:

    • sPGA 0 or 1: 84% vs 5%

    • PASI 90: 75% vs 2%

    • sPGA 0: 51% vs 3%

    • PASI 100: 51% vs 2%

    In both the PsO-1 and PsO-2 studies at week 52, patients treated with Skyrizi also achieved sPGA 0 (58% and 60%, respectively), PASI 90 (82% and 81%, respectively), and PASI 100 (56% and 60%, respectively). 

    Moreover, in both studies, treatment with Skyrizi showed improvements in signs and symptoms related to pain, redness, itching and burning at week 16 compared to placebo as assessed by the PSS. In PsO-1 and PsO-2, about 30% of the subjects who received Skyrizi achieved PSS 0 (“none”) at Week 16 compared to 1% of the subjects who received placebo. 

    Study PsO-3: 507 patients were randomly assigned to receive either Skyrizi (n=407) or placebo (n=100) at weeks 0, 4, and every 12 weeks thereafter. At Week 16, Skyrizi was superior to placebo on the co-primary endpoints of sPGA 0 or 1 (84% Skyrizi and 7% placebo) and PASI 90 (73% Skyrizi and 2% placebo). The respective response rates for Skyrizi and placebo at Week 16 were: sPGA 0 (46% Skyrizi and 1% placebo); PASI 100 (47% Skyrizi and 1% placebo); and PASI 75 (89% Skyrizi and 8% placebo). 

    Maintenance and Durability of Response: In PsO-1 and PsO-2, among the subjects who received Skyrizi and had PASI 100 at Week 16, 80% (206/258) of the subjects who continued on Skyrizi had PASI 100 at Week 52. For PASI 90 responders at Week 16, 88% (398/450) of the patients had PASI 90 at Week 52. 

    In PsO-3, patients who were originally on Skyrizi and had sPGA 0 or 1 at Week 28 were re-randomized to continue Skyrizi every 12 weeks or withdrawal of therapy. At Week 52, 87% (97/111) of the patients re-randomized to continue treatment with Skyrizi had sPGA 0 or 1 compared to 61% (138/225) who were re-randomized to withdrawal of Skyrizi. 

    For more trial data: see full labeling.

    Skyrizi Note

    Not Applicable

    Skyrizi Patient Counseling

    Cost Savings Program

    Skyrizi Patient Support & Resources: https://www.skyrizi.com/skyrizi-complete/save-on-skyrizi-costs

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