Risankizumab

Introduction Overview

Generic Name

risankizumab

Brand Name

Skyrizi

Dosage Form

vial, autoinjector pen, prefilled syringe, prefilled cartridge (supplied on-body injector)

Drug Class

Interleukin inhibitors

Pharmacokinetics

Absorption:
Risankizumab (Skyrizi) is administered primarily via subcutaneous injection for the treatment of plaque psoriasis and psoriatic arthritis, leading to bioavailability typical of monoclonal antibodies delivered via this route. Subcutaneous administration ensures gradual absorption through the lymphatic system with peak plasma concentrations typically reached within several days post-injection. In the intravenous formulation (used for induction in Crohn's disease and ulcerative colitis), absorption is immediate, and peak plasma levels occur at the end of infusion. The bioavailability following subcutaneous administration is high, consistent with monoclonal antibodies, and is unaffected by food intake. Studies have demonstrated consistent absorption profiles in adult patients with varying disease states without significant alteration due to age, sex, or concomitant medications.

Distribution:
Risankizumab exhibits a distribution volume approximating plasma volume (~6–9 L), consistent with its large molecular weight and monoclonal antibody nature. It primarily distributes in the vascular and interstitial spaces with minimal penetration into intracellular compartments. Protein binding is expected to be significant but is specific to the targeted antigen, interleukin-23 (IL-23). Tissue distribution studies indicate that risankizumab localizes to inflamed tissues expressing IL-23, enabling targeted modulation of inflammatory responses. Due to its size, it does not cross the blood-brain barrier appreciably. Distribution characteristics are important clinically as they correlate with therapeutic efficacy and safety.

Metabolism:
As a monoclonal antibody, risankizumab undergoes catabolic degradation predominantly via proteolytic enzymes in the reticuloendothelial system rather than classical hepatic metabolism pathways. The drug is degraded into small peptides and amino acids which are then recycled or eliminated. Cytochrome P450 enzymes are not involved in its metabolism; therefore, risankizumab is unlikely to participate in common pharmacokinetic drug interactions mediated by liver enzyme induction or inhibition. This metabolism pathway ensures a predictable clearance profile and lowers the risk of drug-drug metabolic interactions.

Elimination:
The elimination half-life of risankizumab ranges from approximately 28 to 31 days, allowing for extended dosing intervals (every 8 to 12 weeks depending on indication). Clearance occurs mainly through catabolic processes rather than renal or biliary excretion, which is typical for monoclonal antibodies. Renal or hepatic impairment does not significantly impact the elimination of risankizumab, and dose adjustments are generally not required. Steady-state plasma concentrations are typically achieved after multiple dosing cycles, consistent with the long half-life and dosing schedules. The elimination profile supports convenient dosing regimens that enhance patient adherence.

Dosage Forms

**Available Dosage Forms:**
- Subcutaneous Injection:
- Skyrizi Pen: 150 mg/mL single-dose prefilled pen — colorless to yellow and clear to slightly opalescent solution.
- Skyrizi Prefilled Syringe:
- 150 mg/mL single-dose prefilled syringe.
- 90 mg/mL single-dose prefilled syringe.
- 75 mg/0.83 mL single-dose prefilled syringe (discontinued).
- Skyrizi Prefilled Cartridge with Supplied On-Body Injector:
- 360 mg/2.4 mL (150 mg/mL) single-dose prefilled cartridge.
- 180 mg/1.2 mL (150 mg/mL) single-dose prefilled cartridge.
- Intravenous Infusion:
- Skyrizi Vial: 600 mg/10 mL (60 mg/mL) single-dose vial.

Dosages for Adults and Adolescents:
- Plaque Psoriasis:
- 150 mg subcutaneously at Week 0, Week 4, then every 12 weeks thereafter.
- Psoriatic Arthritis:
- 150 mg subcutaneously at Week 0, Week 4, then every 12 weeks.
- Crohn's Disease:
- Induction: 600 mg intravenously over at least 1 hour at Week 0, Week 4, and Week 8.
- Maintenance: 360 mg subcutaneously via on-body injector at Week 12, then every 8 weeks.
- Ulcerative Colitis:
- Induction: 1200 mg intravenously over at least 2 hours at Week 0, Week 4, and Week 8.
- Maintenance: 180 mg or 360 mg subcutaneously at Week 12, then every 8 weeks using the lowest effective dose.

Specific Patient Populations:
- Pediatric Use: Not approved for patients under 18 years of age.
- Renal or Hepatic Impairment: No dose adjustments required due to nonhepatic and nonrenal clearance.
- Infection Screening: Mandatory tuberculosis evaluation before initiating therapy.
- Vaccinations: Live vaccines should be avoided during treatment.
- Pregnancy and Lactation: Safety not established; register pregnant patients to monitor outcomes.
- Administration Considerations: Allow injections to reach room temperature before use; avoid freezing or shaking; rotate injection sites to minimize local irritation.

Mechanism Of Action

Risankizumab, the active component of Skyrizi, is a humanized monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23), a cytokine that plays a pivotal role in inflammatory and immune-mediated pathways. By targeting IL-23, risankizumab inhibits its interaction with the IL-23 receptor on T-helper 17 (Th17) cells and other immune cells. This blockade prevents the activation and maintenance of the Th17 pathway, which is substantially implicated in the pathogenesis of autoimmune diseases such as plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.

IL-23 is integral to the differentiation and survival of Th17 cells, which produce pro-inflammatory cytokines including IL-17, IL-22, and tumor necrosis factor-alpha (TNF-alpha). These cytokines stimulate keratinocyte activation and neutrophil recruitment, contributing to the chronic inflammatory responses and tissue damage seen in psoriasis and related disorders. By neutralizing IL-23, risankizumab effectively downregulates these downstream inflammatory cascades, leading to symptomatic improvement and disease control.

Clinically, risankizumab's specificity for the p19 subunit distinguishes it from other immunomodulators targeting IL-12/23 pathways (which block both p40 subunits shared by IL-12 and IL-23). This targeted inhibition allows for effective modulation of pathogenic inflammation while preserving IL-12 mediated protective immune functions such as host defense against intracellular pathogens and tumor surveillance, potentially improving safety.

Clinical trials have demonstrated superior efficacy of risankizumab compared to traditional systemic therapies and other biologics such as TNF inhibitors and IL-12/23 inhibitors. Its prolonged half-life and targeted mechanism facilitate convenient dosing schedules. Ongoing research continues to elucidate its impact on immune homeostasis and expanding therapeutic roles.

Pharmacological Actions

Selective inhibition of interleukin-23 (IL-23) by targeting the p19 subunit.
Downregulation of the Th17 cell-mediated pro-inflammatory cytokine cascade.
Reduction of keratinocyte activation and neutrophil recruitment in psoriatic lesions.
Suppression of chronic inflammation in autoimmune diseases such as psoriasis and inflammatory bowel diseases.
Immunomodulation preserving IL-12 mediated immune functions.
Prolonged immunosuppressive effect enabling extended dosing intervals.
Reduction of systemic and local inflammatory markers associated with autoimmunity.
Decreased joint inflammation and damage in psoriatic arthritis.
Improvement of mucosal healing in Crohn’s disease and ulcerative colitis.
Minimal off-target effects due to high monoclonal antibody specificity.
Decreased production of IL-17 and IL-22, key cytokines in autoimmune pathology.
Potential to modify disease progression by controlling underlying immune dysregulation.
Favorable immune profile reducing the risk of widespread immunosuppression.
Immunological blockade that translates into improved clinical remission rates.

Therapeutic Or Clinical Uses

Treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Management of active psoriatic arthritis in adult patients.
Induction and maintenance therapy for moderately to severely active Crohn’s disease in adults.
Induction and maintenance therapy for moderately to severely active ulcerative colitis in adults.
Reduction of inflammatory symptoms and skin lesions associated with autoimmune skin disorders.
Prevention of disease progression in psoriatic arthritis, preserving joint function.
Promotion of mucosal healing and remission in inflammatory bowel diseases.
Alternative treatment option for patients intolerant or unresponsive to TNF inhibitors or other biologics.
Use in patients requiring infrequent dosing schedules due to long elimination half-life.
Therapeutic option with improved safety profile due to IL-23 p19 specificity.
Support for improved quality of life and functional status in autoimmune inflammatory diseases.
Monotherapy or adjunct to other immunomodulating agents pending physician assessment.
Treatment consideration for patients with contraindications to traditional systemic immunosuppressants.

Side Or Adverse Effects

Common side effects include fever, headache, and fatigue.
Gastrointestinal discomfort such as stomach pain and abdominal discomfort.
Musculoskeletal pain, including joint and back pain.
Upper respiratory tract infections presenting as cold-like symptoms (stuffy nose, sneezing, sore throat).
Urinary tract infections manifesting as pain and burning urination.
Fungal skin infections like tinea corporis.
Injection site reactions characterized by pain, bruising, swelling, and irritation.
Anemia manifesting as dizziness, weakness, and shortness of breath in some patients.
Serious infections including potential for fatal infections due to immunosuppression.
Allergic reactions ranging from mild hypersensitivity to severe anaphylaxis.
Hepatotoxicity indicated by nausea, vomiting, jaundice, and abnormal liver enzyme levels.
Potential increased risk of tuberculosis activation or reactivation.
Rare but serious skin reactions and rashes.
Potential for immunogenicity leading to reduced drug efficacy over time.
Possible respiratory symptoms such as cough or shortness of breath linked to infection.

Precautions

Assess patients for tuberculosis infection before initiating therapy and monitor periodically.
Avoid use in patients with active or chronic infections until infections are controlled.
Monitor liver function tests prior to and during treatment due to risk of hepatotoxicity.
Patients should be current with all vaccinations prior to treatment; live vaccines are contraindicated during therapy.
Use cautiously in patients with a history of liver disease including cirrhosis.
Pregnancy use only if clearly needed; enroll patients in pregnancy registries to monitor outcomes.
Safety in pediatric patients (<18 years) has not been established; use is not approved in this population.
Avoid administration in patients with known hypersensitivity to risankizumab or formulation components.
Educate patients on sterile technique and proper injection rotation to minimize injection site reactions.
Monitor for signs and symptoms of serious infection and provide prompt medical evaluation.
Consider risk-benefit assessment in immunocompromised patients or those receiving concomitant immunosuppressants.
Avoid abrupt discontinuation to prevent loss of disease control; manage dosing schedule carefully.
Counsel patients regarding potential delayed onset of therapeutic effects.
Patients should not refrigerate the drug after it has been allowed to reach room temperature for injection.
Ensure proper disposal of sharps and used injection devices according to local regulations.

Warnings

Skyrizi suppresses the immune system and increases susceptibility to serious and potentially fatal infections.
Avoid use in patients with active severe infections such as tuberculosis, sepsis, or opportunistic infections.
Patients should be monitored for signs of infection during and after treatment, including fever and respiratory symptoms.
Allergic reactions including anaphylaxis have been reported; discontinue drug and seek emergency care if they occur.
Risk of hepatotoxicity mandates regular monitoring of liver enzymes and bilirubin during treatment.
Do not use Skyrizi concurrently with live vaccines due to risk of vaccine-related infection.
Potential for delayed hypersensitivity reactions; patients should report new rash or systemic symptoms.
Not approved for use in patients under 18 years of age; safety and efficacy have not been established.
Patients with preexisting immune conditions require careful evaluation prior to therapy initiation.
Discontinue Skyrizi if a serious infection develops until infection resolves.
Use with caution in patients receiving concomitant immunosuppressive therapy due to additive immunosuppression.
Avoid abrupt cessation without medical advice to reduce risk of disease flare or rebound.
Monitor for malignancy as immunomodulatory agents may carry increased risk, though no cancer signal noted with Skyrizi.
Pregnant or breastfeeding women should weigh potential risks and benefits with their healthcare provider.
Educate patients on recognizing early symptoms of complications and when to seek medical attention.

Contraindication

Known hypersensitivity or allergic reactions to risankizumab, Skyrizi, or any components of the formulation.
Active severe infections, including tuberculosis, sepsis, or other systemic infections.
Concurrent administration of live vaccines due to immunosuppressive effects.
Patients with hypersensitivity to any monoclonal antibody therapy targeting cytokine pathways.
Use in pediatric patients younger than 18 years is contraindicated due to lack of established safety and efficacy.
Known severe liver impairment or active hepatic disease until stabilized and evaluated carefully.
Patients with a history of severe allergic reactions or anaphylaxis to biologic immunomodulators.
Pregnant women should avoid use unless benefit outweighs risk after thorough discussion with healthcare provider.
Known immunodeficiency syndromes or concurrent participation in other immune suppressive clinical trials unless specified.
Patients with uncontrolled chronic infections until effectively treated.
Patients currently receiving other immunosuppressive biologics without appropriate washout periods.

Drug Interactions

No significant cytochrome P450-mediated drug interactions due to monoclonal antibody metabolism.
Potential additive immunosuppression when combined with other immunomodulatory agents (e.g., TNF inhibitors, methotrexate).
Live vaccines contraindicated during treatment due to immunosuppression increasing risk of vaccine-related infection.
Concomitant use with strong immunosuppressants requires careful monitoring for infection risk.
No known interactions with commonly used non-immunosuppressive medications.
No dose adjustments required for concomitant administration of routine medications based on current data.
Herbal products and vitamins have not demonstrated interaction but should be reported to healthcare providers.
Co-administration with other biologics targeting similar cytokine pathways not recommended due to unknown safety.
No reported impact on hormonal contraceptives or other standard therapies.
No clinically relevant interactions noted with analgesics or antifungal agents.
Patients should inform providers of all medications to assess potential unrecognized interactions.
Close monitoring advised if combined with medications that increase infection risk or alter immune response.
Limited clinical data on drug-drug interactions with risankizumab; clinicians should exercise caution.
No effect on metabolism or excretion of other concurrently administered drugs has been observed.

Preparations Of The Drug

Skyrizi Pen: single-dose prefilled pen delivering 150 mg/mL solution for subcutaneous injection.
Skyrizi Prefilled Syringe: single-dose syringes available in concentrations 150 mg/mL, 90 mg/mL, and discontinued 75 mg/0.83 mL formulation.
Skyrizi Prefilled Cartridge: supplied with on-body injector device in doses of 360 mg/2.4 mL and 180 mg/1.2 mL (150 mg/mL) for subcutaneous injection.
Skyrizi Vial: 600 mg/10 mL (60 mg/mL) single-dose vial for intravenous infusion during induction therapy.
Formulations contain inactive ingredients such as glacial acetic acid, polysorbate 20, sodium acetate, trehalose, sodium succinate, sorbitol, succinic acid, and Water for Injection, USP.
All preparations are free from natural rubber latex.
Solutions appear colorless to yellow and clear to slightly opalescent.
Packaging includes original cartons to protect product from light and maintain stability.
Prefilled syringes and pens are single-use and should be properly discarded after administration.
The on-body injector aids in patient self-administration by delivering a controlled subcutaneous dose over a set duration.
All formulations require refrigeration between 2°C to 8°C (36°F to 46°F) and should not be frozen or shaken.
Diluted intravenous preparations must be infused over prescribed durations and used within stability windows.
Instructions for use provide detailed guidance on injection technique, site selection, and device handling for patient safety.
Manufactured by AbbVie Inc., ensuring consistency and quality control across all drug preparations.
Detailed prescribing information is available to guide medical professionals on indications, dosing, and administration.