Ixekizumab (Monograph)

Brand name: Taltz
Drug class: Disease-modifying Antirheumatic Drugs
Chemical name: Disulfide with human monoclonal LY2439821 κ-chain anti-(human interleukin 17A) (human monoclonal LY2439821 γ4-chain) immunoglobulin G4 dimer
Molecular formula: C₆₄₉₂H₁₀₀₁₂N₁₇₂₈O₂₀₂₈S₄₆
CAS number: 1143503-69-8

Medically reviewed by Drugs.com on Jun 23, 2022. Written by ASHP.

Introduction

Inhibitor of interleukin-17A (IL-17A), a proinflammatory cytokine; a recombinant humanized IgG₄ kappa monoclonal antibody specific for IL-17A.

Uses for Ixekizumab

Plaque Psoriasis

Management of moderate to severe plaque psoriasis in adults and pediatric patients ≥6 years of age who are candidates for phototherapy or systemic therapy.

Adult guidelines generally support the use of IL-17 blocking agents as monotherapy for treatment of moderate to severe psoriasis.

Pediatric guidelines have not yet incorporated recommendations for use of IL-17 blocking agents for the treatment of pediatric plaque psoriasis.

Recommendations for use and selection of psoriasis therapies vary based on patient age, disease characteristics (e.g., severity, location, presence of psoriatic arthritis), and comorbidities (e.g., inflammatory bowel disease).

Psoriatic Arthritis

Management of active psoriatic arthritis in adults.

Disease-modifying treatments for psoriatic arthritis include oral small molecules (OSMs; e.g., methotrexate, sulfasalazine, cyclosporine, leflunomide, apremilast), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab, ustekinumab, brodalumab, abatacept), and/or targeted synthetic DMARDs (e.g., tofacitinib).

Guidelines generally support the use of the IL-17 blocking agents as second-line therapy after TNF inhibitors for treatment of psoriatic arthritis.

Recommendations for the use and selection of disease-modifying therapies in psoriatic arthritis vary based on the presence of certain disease characteristics (e.g., psoriatic spondylitis/axial disease, enthesitis) and comorbidities (e.g., inflammatory bowel disease, diabetes).

Ankylosing Spondylitis

Management of active ankylosing spondylitis in adults.

Treatments for ankylosing spondylitis include NSAIAs, conventional DMARDs (e.g., methotrexate, sulfasalazine), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab), and/or targeted synthetic DMARDs (e.g., tofacitinib).

Guidelines generally support the use of IL-17 inhibitors as second-line therapy after TNF blocking agents for the treatment of ankylosing spondylitis in patients with active disease despite treatment with NSAIAs.

Recommendations for treatment selection in ankylosing spondylitis vary based on the presence of certain comorbidities (e.g., iritis, inflammatory bowel disease).

Nonradiographic Axial Spondyloarthritis

Management of active nonradiographic axial spondyloarthritis in adults with objective signs of inflammation.

Recommendations for the treatment of nonradiographic axial spondyloarthritis are largely extrapolated from evidence in the treatment of ankylosing spondylitis. Guidelines generally support the use of IL-17 inhibitors, including ixekizumab, as second-line therapy after TNF blocking agents in patients with active disease despite treatment with NSAIAs.

Ixekizumab Dosage and Administration

General

Pretreatment Screening

Evaluate for tuberculosis infection prior to initiation of ixekizumab. Do not administer to patients with active tuberculosis infection. Initiate antimycobacterial therapy of latent tuberculosis prior to administering ixekizumab. Consider antimycobacterial therapy prior to initiating ixekizumab in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Administer all age-appropriate vaccines prior to starting ixekizumab therapy.

Patient Monitoring

Monitor closely for signs or symptoms of infection or active tuberculosis during and after treatment with ixekizumab.
Monitor for signs and symptoms of inflammatory bowel disease during treatment.

Other General Considerations

Ixekizumab may be used alone or in combination with conventional DMARDs (e.g., methotrexate) for the treatment of psoriatic arthritis.

Administration

Sub-Q Administration

Administer by sub-Q injection into the upper arms, thighs, or any quadrant of the abdomen; do not make abdominal injections within 1 inch of the navel. Administration into upper outer arm may be performed by a caregiver or clinician.

Rotate injection sites.

Do not make injections into areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis.

Intended for use under the guidance and supervision of a clinician, but may be self-administered in adults if clinician determines the patient and/or caregiver is competent to safely administer the drug after appropriate training. A caregiver may administer to pediatric patients >50 kg after appropriate training.

Administration into the thigh resulted in higher bioavailability compared with other injection sites, including the arm and abdomen.

Use of Prefilled Autoinjector or Prefilled Syringe

Remove prefilled autoinjector or prefilled syringe from refrigerator and allow to sit at room temperature protected from light for 30 minutes prior to injection. Do not warm solution by placing in microwave, running hot water over the autoinjector or syringe, or exposing the injection to direct sunlight. Do not remove the base cap of the autoinjector or the needle cap of the syringe while the autoinjector or prefilled syringe is warming to room temperature.

Inject entire contents of the autoinjector or prefilled syringe (1 mL providing 80 mg).

Do not shake the solution.

Discard any unused portions of solution.

Dose Preparation for Pediatric Patients Weighing ≤50 kg

Pediatric dosages must be prepared and administered by a healthcare professional. Use the 80 mg/1 mL prefilled syringe only to prepare the dose.

To prepare the dose, use a 0.5 mL or 1 mL disposable syringe, a sterile needle for withdrawal of the drug, a 27-gauge sterile needle for administration, and a sterile, clear glass vial.

Expel entire contents of the 80 mg/1 mL prefilled syringe into a sterile, clear glass vial. Do not shake or swirl the vial or add other medications. Withdraw the appropriate dose (0.25 mL for a 20-mg dose or 0.5 mL for a 40-mg dose) using the disposable syringe and sterile needle. Remove sterile needle and replace with 27-gauge sterile needle for administration.

Dosage

Pediatric Patients

Plaque Psoriasis

Sub-Q

Dosing of ixekizumab in pediatric patients is weight-based:

<25 kg: 40 mg at week 0, followed by 20 mg once every 4 weeks.

25–50 kg: 80 mg at week 0, followed by 40 mg once every 4 weeks.

>50 kg: 160 mg (two 80-mg injections) at week 0, followed by 80 mg once every 4 weeks.

Adults

Plaque Psoriasis

Sub-Q

160 mg (two 80-mg injections) at week 0 and then 80 mg at weeks 2, 4, 6, 8, 10, and 12, followed by 80 mg every 4 weeks thereafter.

Psoriatic Arthritis

Sub-Q

160 mg (two 80-mg injections) at week 0, followed by 80 mg every 4 weeks thereafter. If patient has coexisting psoriatic arthritis and moderate to severe plaque psoriasis, use dosage recommended for plaque psoriasis.

Ankylosing Spondylitis

Sub-Q

160 mg (two 80-mg injections) at week 0, followed by 80 mg every 4 weeks thereafter.

Nonradiographic Axial Spondyloarthritis.

Sub-Q

80 mg every 4 weeks.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Ixekizumab

Contraindications

History of serious hypersensitivity reactions (e.g,. anaphylaxis) to ixekizumab or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity

Serious hypersensitivity reactions (e.g., angioedema, urticaria, anaphylaxis) reported. If a serious hypersensitivity reaction occurs, discontinue ixekizumab immediately and initiate appropriate supportive treatment.

Infectious Complications

Increased risk of infections in patients with plaque psoriasis, pediatric psoriasis, psoriatic arthritis, ankylosing spondylitis, or nonradiographic axial spondyloarthritis.

Neutropenia, generally grade 1 or 2, reported in clinical trials in patients with plaque psoriasis; however, not associated with increased rate of infection.

If a serious infection develops or if an infection fails to respond to standard therapy, monitor patient closely and discontinue ixekizumab until the infection resolves.

Evaluate patients for tuberculosis before initiating ixekizumab. Do not administer to patients with active tuberculosis infection. When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection before initiating ixekizumab. Also consider antimycobacterial therapy before initiating ixekizumab for patients with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed. Closely monitor patients for signs and symptoms of active tuberculosis during and after ixekizumab treatment.

Inflammatory Bowel Disease

Crohn’s disease and ulcerative colitis, including exacerbations, reported more frequently in patients receiving ixekizumab compared with those receiving placebo. Some events may be serious. Monitor for onset or exacerbation of inflammatory bowel disease.

Discontinue ixekizumab if inflammatory bowel disease occurs and initiate appropriate medical management.

Immunization

Consider administering all age-appropriate vaccines recommended by current immunization guidelines before initiating ixekizumab.

Avoid live vaccines during therapy.

No available data regarding response to live vaccines in patients receiving ixekizumab.

Immunogenicity

Antibodies to ixekizumab, including neutralizing antibodies, reported. Neutralizing antibodies associated with decreased drug concentrations and decreased clinical response or loss of efficacy in adult patients with plaque psoriasis.

Specific Populations

Pregnancy

Data regarding use and associated risks in pregnant women not available. Potential for fetal exposure since human IgG crosses the placenta and ixekizumab crossed the placenta in monkeys.

In studies in cynomolgus monkeys, no evidence of adverse embryofetal developmental effects; however, increased neonatal deaths observed when administration continued until parturition. No adverse effects on functional or immunologic development observed from birth through 6 months of age.

Lactation

Not known whether ixekizumab distributes into human milk, affects human milk production, or affects breast-fed infant. Ixekizumab distributes into milk in cynomolgus monkeys.

Consider benefits of breast-feeding and importance of the drug to the woman; also consider any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients <6 years of age for plaque psoriasis and in pediatric patients <18 years of age for all other indications.

Geriatric Use

No apparent differences in safety or efficacy between geriatric patients and younger adults with psoriasis; however, insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.

Hepatic Impairment

No formal studies to date.

Renal Impairment

No formal studies to date.

Common Adverse Effects

Injection site reactions, upper respiratory tract infections (e.g., nasopharyngitis, rhinovirus infection), nausea, tinea infections.

Interactions for Ixekizumab

Drugs Metabolized by Hepatic Microsomal Enzymes

No clinically significant changes to exposure of a CYP1A2 substrate, CYP2C9 substrate, CYP2C19 substrate, or a CYP3A substrate observed when administered concomitantly with ixekizumab.

Potential effect of ixekizumab on CYP2D6 activity cannot be ruled out.

Vaccines

Avoid live vaccines. No data available regarding response to vaccines in patients receiving ixekizumab.

Specific Drugs

Drug	Interaction	Comments
Adalimumab	Ixekizumab clearance not affected by prior adalimumab use in patients with psoriatic arthritis
Caffeine	No clinically relevant pharmacokinetic interaction
Corticosteroids	Ixekizumab clearance not affected by concomitant oral corticosteroid use in patients with ankylosing spondylitis

Dextromethorphan	Highly variable exposure to dextromethorphan and its metabolite dextrorphan in patients with psoriasis
Methotrexate	Ixekizumab clearance not affected by concomitant or prior methotrexate use in patients with psoriatic arthritis or concomitant methotrexate use in patients with ankylosing spondylitis and nonradiographic axial spondyloarthritis
Midazolam	No clinically relevant pharmacokinetic interaction
NSAIAs	Ixekizumab clearance not affected by concomitant NSAIA use in patients with ankylosing spondylitis
Omeprazole	No clinically relevant pharmacokinetic interaction
Sulfasalazine	Ixekizumab clearance not affected by concomitant sulfasalazine use in patients with ankylosing spondylitis and nonradiographic axial spondyloarthritis
Warfarin	No clinically relevant pharmacokinetic interaction

Ixekizumab Pharmacokinetics

Absorption

Bioavailability

Bioavailability is 60–81% following sub-Q administration. Higher bioavailability attained when administered into thigh compared with other injection sites, including arm and abdomen.

Peak plasma concentrations achieved by approximately 4 days after a single 160-mg sub-Q dose.

Steady-state concentrations attained by week 8 in patients receiving initial 160-mg dose followed by 80 mg every 2 weeks. After dosage changed at week 12 to 80 mg every 4 weeks, new steady state achieved in approximately 10 weeks.

Pharmacokinetics are dose proportional over a sub-Q dose range of 5–160 mg.

Distribution

Extent

Not known whether distributed into human milk.

Special Populations

Volume of distribution increases as body weight increases.

Elimination

Metabolism

Metabolic pathway not characterized.

Expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Half-life

13 days.

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.

Age does not substantially alter clearance in adults with plaque psoriasis.

Pharmacokinetics similar in adult patients with plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, or nonradiographic axial spondyloarthritis.

Clearance increases as body weight increases.

Stability

Storage

Parenteral

Injection

Autoinjector or prefilled syringe: 2–8°C. Keep in original carton and protect from light. Do not freeze.

When using packages containing multiple autoinjectors, remove only a single autoinjector from the package at one time; leave the remaining autoinjectors in the original carton in the refrigerator.

If necessary, may store injection at room temperature (up to 30°C) in original carton for up to 5 days prior to use; do not return injection to refrigerator after storage at room temperature; discard if not used within 5 days.

Actions

Binds to IL-17A and inhibits interaction with the IL-17 receptor.
Elevated levels of IL-17A found in psoriatic lesions and blood of individuals with psoriasis.
Neutralizes biologic activity of IL-17A and inhibits release of proinflammatory cytokines and chemokines.

Advice to Patients

Provide all patients and/or caregivers with a copy of the manufacturer's patient information (medication guide) and instructions for use for ixekizumab with each prescription of the drug. Importance of reading the medication guide and instructions for use prior to initiation of therapy and each time the prescription is refilled.
Instruct patient and/or caregiver regarding proper storage, dosage, and administration of ixekizumab, including the use of aseptic technique, as well as proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.
If a dose of ixekizumab is missed, instruct patient to administer the missed dose as soon as possible and then resume the regular dosing schedule.
Increased susceptibility to infection. Advise patient to promptly inform their clinician if any signs or symptoms of infection (e.g., fever, sweats, or chills; muscle aches; cough, shortness of breath, or blood in the phlegm; weight loss; warm, red, or painful sores on the body; diarrhea or stomach pain; burning upon urination or increased urination) occur.
Advise patient to inform their clinician if new or worsening symptoms of inflammatory bowel disease (e.g., abdominal pain, diarrhea, weight loss) occur.
Advise patient to review their vaccination status with clinician and receive all appropriate vaccines prior to initiation of ixekizumab.
Advise patient to immediately seek medical attention if symptoms of a serious allergic reaction (e.g., feeling of faintness; swelling of eyelids, face, lips, mouth, tongue, or throat; dyspnea or throat tightness; chest tightness; rash) occur.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., active infection, inflammatory bowel disease) or any history of tuberculosis or other infections.
Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.