Crohn disease, moderate to severe, induction and maintenance of remission: Note: Combination with an immunomodulator is generally preferred (al Hashash 2021).
Induction: IV:
≤55 kg: 260 mg as single dose
>55 kg to 85 kg: 390 mg as single dose
>85 kg: 520 mg as single dose
Maintenance: SUBQ: 90 mg every 8 weeks; begin maintenance dosing 8 weeks after the IV induction dose.
Plaque psoriasis: SUBQ:
Initial and maintenance:
≤100 kg: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter. Note: Some patients may require doses of 90 mg or maintenance dosing every 8 weeks (AAD/NPF [Menter 2019]).
>100 kg: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter. Note: Some patients may require maintenance dosing every 8 weeks (AAD/NPF [Menter 2019]).
Psoriatic arthritis: SUBQ: Note: When used for psoriatic arthritis, may be administered alone or in combination with methotrexate.
Initial and maintenance: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter.
Coexistent psoriatic arthritis and moderate to severe plaque psoriasis in patients >100 kg: Initial and maintenance: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter. Note: Some patients may require maintenance dosing every 8 weeks (AAD/NPF [Menter 2019]).
Ulcerative colitis:
Induction: IV:
≤55 kg: 260 mg as single dose.
>55 kg to 85 kg: 390 mg as single dose.
>85 kg: 520 mg as single dose.
Maintenance: SUBQ: 90 mg every 8 weeks; begin maintenance dosing 8 weeks after the IV induction dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Ustekinumab: Pediatric drug information")
Note: Dosing presented in mg/kg and fixed mg; use extra precaution to ensure dosing units.
Inflammatory bowel disease, moderate to severe; refractory: Limited data available (Bishop 2016; Dayan 2019): Note: Dosing varies by route of administration (IV or SUBQ); use extra caution.
Children ≥12 years and Adolescents:
Induction:
<55 kg: IV: 260 mg as single dose.
≥55 to 85 kg: IV: 390 mg as single dose.
>85 kg: IV: 520 mg as single dose.
Maintenance: SUBQ: 90 mg every 8 weeks; begin maintenance dosing 8 weeks after the IV induction dose.
Dosing based on retrospective studies and case reports. A retrospective study of 52 adolescent and young adult (<21 years) patients (median: 16.8 years; 38 patients <18 years of age) diagnosed with inflammatory bowel disease (n=42 Crohn disease; n=10 ulcerative colitis or unspecified) with a majority (81%) having failed previous tumor necrosis factor (TNF)-modulator therapy, utilized a single-dose weight-based IV induction protocol of ustekinumab in most patients (47/52, 90%); the other subjects (5) received subcutaneous induction prior to availability of IV product. Following induction, all patients received fixed dose (regardless of weight) SUBQ maintenance therapy (90 mg every 8 weeks). Results showed at the end of 52 weeks, 58% of patients had achieved steroid-free remission and 65% had achieved clinical remission. At week 52, of the 39 patients who continued on ustekinumab, 62% of patients required dosing every 4 to 7 weeks to maintain remission (Dayan 2019). In a retrospective case series, 4 patients (ages 12 to 17 years) who had failed or unable to tolerate previous TNF modifiers received subcutaneous induction doses of 90 mg every 4 weeks for 2 doses, followed by 90 mg every 8 weeks. Two patients were able to wean off steroid regimens and had clinical improvement and 2 patients were unresponsive to therapy (Bishop 2016).
Plaque psoriasis, moderate to severe:
Children ≥6 years and Adolescents <18 years:
<60 kg: SUBQ: Initial: 0.75 mg/kg at 0 and 4 weeks, followed by maintenance dose of 0.75 mg/kg every 12 weeks.
≥60 to ≤100 kg: SUBQ: Initial: 45 mg at 0 and 4 weeks, followed by maintenance dose of 45 mg every 12 weeks.
>100 kg: SUBQ: Initial: 90 mg at 0 and 4 weeks, followed by maintenance dose of 90 mg every 12 weeks.
Adolescents ≥18 years:
≤100 kg: SUBQ: Initial: 45 mg at 0 and 4 weeks, followed by maintenance dose of 45 mg every 12 weeks.
>100 kg: SUBQ: Initial: 90 mg at 0 and 4 weeks, followed by maintenance dose of 90 mg every 12 weeks.
Psoriatic arthritis, active:
Children ≥6 years and Adolescents <18 years:
<60 kg: SUBQ: Initial: 0.75 mg/kg at 0 and 4 weeks, followed by maintenance dose of 0.75 mg/kg every 12 weeks.
≥60 kg: SUBQ: Initial: 45 mg at 0 and 4 weeks, followed by maintenance dose of 45 mg every 12 weeks.
>100 kg and moderate to severe plaque psoriasis comorbidity: SUBQ: Initial: 90 mg at 0 and 4 weeks, followed by maintenance dose of 90 mg every 12 weeks.
Adolescents ≥18 years: Initial: 45 mg at 0 and 4 weeks, followed by maintenance dose of 45 mg every 12 weeks.
Moderate to severe plaque psoriasis comorbidity and weight >100 kg: SUBQ: Initial: 90 mg at 0 and 4 weeks, followed by maintenance dose of 90 mg every 12 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Stelara: 130 mg/26 mL (26 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Solution, Subcutaneous [preservative free]:
Stelara: 45 mg/0.5 mL (0.5 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Stelara: 45 mg/0.5 mL (0.5 mL); 90 mg/mL (1 mL) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Stelara: 130 mg/26 mL (26 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Stelara: 45 mg/0.5 mL (0.5 mL); 90 mg/mL (1 mL) [contains polysorbate 80]
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Stelara: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125261s161lbl.pdf#page=37
IV: Infuse over at least 1 hour; use of IV set with an in-line, low-protein binding filter (0.2 micrometer) required. Do not infuse concomitantly in the same IV line with other agents.
SUBQ: Administer by subcutaneous injection into the top of the thigh, abdomen, upper arms, or buttocks. Rotate sites. Do not inject into tender, bruised, erythematous, or indurated skin. Avoid areas of skin where psoriasis is present. Discard any unused portion. Intended for use under supervision of physician; self-injection may occur after proper training. If using the single-dose vial, a 1 mL syringe with a 27-gauge 1/2 inch needle is recommended.
Parenteral:
IV: Vials (5 mg/mL) must be diluted prior to administration. Infuse over at least 1 hour; use an IV set with an in-line, low-protein binding filter (0.2 micrometer). Do not infuse concomitantly in the same IV line with other agents; based on adult recommendations and pediatric (age ≥12 years) trial experience which utilized adult dose (Dayan 2019).
SUBQ: Appropriate dosage form dependent on patient weight:
Weight <60 kg: Single-dose vial (45 mg/0.5 mL) using a 1 mL syringe with a 27-gauge, 1/2-inch needle.
Weight ≥60 kg: Prefilled syringes may be used.
Administer by SUBQ injection into the top of the thigh, abdomen, upper arms, or buttocks. Rotate sites. Do not inject into tender, bruised, erythematous, or indurated skin. Avoid areas of skin where psoriasis is present. Discard any unused portion. Pediatric patients should have doses administered by a health care professional.
Crohn disease: Treatment of moderately to severely active Crohn disease in adults.
Guideline recommendations: The American Gastroenterological Association (AGA) guidelines on the medical management of moderate to severe luminal and perianal fistulizing Crohn disease recommends the use of ustekinumab with or without an immunomodulator for in treatment-naïve patients, or in patients with primary- or secondary- non-response to TNF-alpha inhibitors. In addition, ustekinumab may be used in combination with an antibiotic in patients with fistulizing disease for induction or maintenance of fistula remission (AGA [Feuerstein 2021]).
Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in patients ≥6 years of age who are candidates for phototherapy or systemic therapy.
Psoriatic arthritis: Treatment of active psoriatic arthritis in patients ≥6 years of age.
Ulcerative colitis: Treatment of moderately to severely active ulcerative colitis in adults.
Stelara may be confused with Aldara
Ustekinumab may be confused with infliximab, rituximab
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults with plaque psoriasis, psoriatic arthritis, Crohn disease, and/or ulcerative colitis unless otherwise indicated.
>10%:
Immunologic: Antibody development (3% to 12%; associated with reduced efficacy in psoriasis patients)
Infection: Infection (psoriasis: 27% to 72%, rates may vary for other indications; serious infection: 3%)
Respiratory: Nasopharyngitis (7% to 24%)
1% to 10%:
Dermatologic: Acne vulgaris (Crohn disease: 1%), pruritus (2% to 4%)
Gastrointestinal: Abdominal pain (ulcerative colitis: 7%), diarrhea (ulcerative colitis: 4%), nausea (3%), vomiting (Crohn disease: 4%)
Genitourinary: Urinary tract infection (≤4%), vaginal mycosis (Crohn disease: ≤5%), vulvovaginal candidiasis (Crohn disease: ≤5%)
Hematologic & oncologic: Malignant neoplasm (excluding nonmelanoma: ≤2%), skin carcinoma (nonmelanoma including squamous cell carcinoma; psoriasis: 2%)
Infection: Influenza (≤6%)
Local: Erythema at injection site (1% to 5%)
Nervous system: Asthenia (Crohn disease: 1%), depression (psoriasis: 1%), dizziness (psoriasis: 2%), fatigue (3% to 4%), headache (5% to 10%)
Neuromuscular & skeletal: Arthralgia (psoriatic arthritis: 3%), back pain (psoriasis: 2%)
Respiratory: Bronchitis (≤5%), pharyngolaryngeal pain (psoriasis: 2%), sinusitis (3% to 4%)
Miscellaneous: Fever (ulcerative colitis: 5%)
<1%:
Dermatologic: Cellulitis
Gastrointestinal: Diverticulitis of the gastrointestinal tract
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Infection: Herpes zoster infection
Local: Bleeding at injection site, bruising at injection site, induration at injection site, injection-site pruritus, irritation at injection site, pain at injection site, swelling at injection site
Nervous system: Meningitis due to Listeria monocytogenes, reversible posterior leukoencephalopathy syndrome
Ophthalmic: Ocular herpes simplex
Frequency not defined:
Gastrointestinal: Abscess of rectum and/or peri-rectal area, appendicitis, cholecystitis, gastroenteritis
Infection: Sepsis, viral infection
Neuromuscular & skeletal: Osteomyelitis
Respiratory: Pneumonia
Postmarketing:
Dermatologic: Erythrodermic psoriasis, pustular psoriasis
Hypersensitivity: Angioedema, hypersensitivity angiitis
Infection: Atypical mycobacterial infection, bacterial infection, fungal infection (including opportunistic)
Nervous system: Intracranial hypertension (Tan 2020)
Respiratory: Bronchiolitis obliterans organizing pneumonia, eosinophilic pneumonitis, interstitial pneumonitis, lower respiratory tract infection, tuberculosis
Clinically significant hypersensitivity to ustekinumab or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Severe infections such as sepsis, tuberculosis, and opportunistic infections
Concerns related to adverse effects:
• Antibody formation: Formation of neutralizing anti-drug antibodies may occur with ustekinumab and may be associated with loss of efficacy (AAD/NPF [Menter 2019]).
• Hypersensitivity reactions: Hypersensitivity, including anaphylaxis and angioedema, has been reported. Discontinue immediately with signs/symptoms of hypersensitivity reaction and treat appropriately as indicated.
• Infections: May increase the risk for infections or reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections have been observed with use. Avoid use in patients with clinically important active infection until the infection resolves or is successfully treated. Exercise caution when considering use in patients with a history of new/recurrent infections, with conditions that predispose them to infections (eg, diabetes or residence/travel from areas of endemic mycoses), with chronic, latent, or localized infections, or who are genetically deficient in IL-12/IL-23 (IL-12/IL-23 genetic deficiency may predispose patients to disseminated infection). Patients who develop a new infection while undergoing treatment should consult their health care provider and be monitored closely. If a patient develops a serious infection, therapy should be discontinued or withheld until successful resolution of infection.
• Malignancy: May increase the risk for malignancy although the impact on the development and course of malignancies is not fully defined. Rapidly appearing cutaneous squamous cell carcinomas (multiple) have been reported in patients receiving ustekinumab who were at risk for developing nonmelanoma skin cancer. Monitor all patients closely for the development of nonmelanoma skin cancer; closely follow patients >60 years of age, with a history of prolonged immunosuppression, and in patients with a history of PUVA treatment. Use with caution in patients with prior malignancy (use not studied in this population).
• Noninfectious pneumonia: Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia, some leading to respiratory failure and prolonged hospitalization, have been reported; most commonly has occurred within the first few doses. Symptoms may include cough, dyspnea, and interstitial infiltrates. Discontinue therapy and institute appropriate treatment if noninfectious pneumonia is suspected or confirmed.
• Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has been reported. Symptoms of PRES include confusion, headache, imaging changes, seizure, and visual disturbances; most cases occur within a few days to several months after initiation of therapy but may occur ≥1 year. Monitor patients closely; discontinue therapy immediately if symptoms occur and administer appropriate therapy.
• Tuberculosis: Do not use in patients with active tuberculosis (TB). Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to starting therapy. Treatment of latent TB should be initiated before ustekinumab therapy is used. Consider antituberculosis treatment in patients with a history of latent or active tuberculosis if an adequate prior treatment course cannot be confirmed. During and following treatment, monitor for signs/symptoms of active TB.
Concurrent drug therapy issues:
• Allergen immunotherapy: Use caution in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis; ustekinumab may decrease the protective effect of allergen immunotherapy, which may increase the risk of an allergic reaction to allergen immunotherapy.
• Immunosuppressive therapy: Use in combination with other immunosuppressive drugs during psoriasis studies has not been evaluated; use caution. Use in combination with methotrexate during psoriatic arthritis studies did not appear to affect safety or efficacy.
Special populations:
• Patients >100 kg: May require higher dose to achieve adequate serum levels.
Dosage form specific issues:
• Latex: Packaging may contain natural latex rubber.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Although the manufacturer suggests that live vaccines should not be given concurrently, expert consensus recommends that ustekinumab be held for one dosing interval (the longest described in labeling) prior to administration of a live vaccine and then ustekinumab be held 4 weeks after administration of a live vaccine in general; individualized consideration should be given to patient risk for vaccine preventable illness and for disease flares if immunosuppressant therapy held (ACR 2022). Inactivated or nonlive vaccines may be given concurrently, but may not elicit a proper immune response. BCG vaccines should not be given 1 year prior to, during, or 1 year following treatment.
• Phototherapy: Use in combination with phototherapy has not been studied; use caution.
Reactivation of tuberculosis (TB) has been reported in pediatric patients receiving biologic response modifiers (infliximab and etanercept); prior to therapy, patients with no TB risk factors should be screened for latent TB infection (LTBI) with an age appropriate test (ie, <5 years of age: Tuberculin skin test; ≥5 years of age: IGRA [interferon gamma release assay]); if any TB risk factors are present or symptoms, both LTBI screening tests should be performed (AAP [Davies 2016]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Anifrolumab: Biologic Anti-Psoriasis Agents may enhance the immunosuppressive effect of Anifrolumab. Risk X: Avoid combination
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Ustekinumab may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of infection may be increased. Ustekinumab may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Belimumab: May enhance the immunosuppressive effect of Biologic Anti-Psoriasis Agents. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
InFLIXimab: May enhance the immunosuppressive effect of Biologic Anti-Psoriasis Agents. Risk X: Avoid combination
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
The American Academy of Dermatology considers ustekinumab for the treatment of psoriasis to be acceptable for use in patients planning to father a child (AAD/NPF [Menter 2019]).
Females and males with well-controlled psoriasis who are planning a pregnancy and wish to avoid fetal exposure can consider discontinuing ustekinumab 15 weeks prior to attempting pregnancy (Rademaker 2018).
Inflammatory bowel disease is associated with adverse pregnancy outcomes; maternal disease and serum levels of biologic therapy should be optimized prior to conception. Biologics, such as ustekinumab, may be continued in patients with inflammatory bowel disease planning to become pregnant (Mahadevan 2019). Treatment algorithms are available for use of biologics in patients with Crohn disease who are planning to become pregnant (Weizman 2019).
Based on limited information, use of ustekinumab may be continued through conception in patients with rheumatic and musculoskeletal diseases who are planning a pregnancy and not able to use alternative therapies; use should be discontinued once pregnancy is confirmed. Conception should be planned during a period of quiescent/low disease activity. Recommendations for use of ustekinumab to treat rheumatic and musculoskeletal diseases in patients who are planning to father a child are not available due to limited data (ACR [Sammaritano 2020]).
Ustekinumab crosses the placenta (Klenske 2019; Rowan 2018).
Ustekinumab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Following administration to two pregnant patients with Crohn disease, cord blood concentrations of ustekinumab were ~2 to 4 times higher than maternal trough levels at delivery. In both cases, ustekinumab was administered throughout pregnancy and stopped 4 to 8 weeks prior to delivery (Klenske 2019; Rowan 2018). In one case, maternal trough concentrations remained stable throughout pregnancy (Rowan 2018).
Vaccination with live vaccines (eg, rotavirus vaccine) should be avoided for the first 6 months of life if exposure to a biologic agent occurs during the third trimester of pregnancy (eg, >27 weeks' gestation) (Mahadevan 2019).
The American Academy of Dermatology considers the safety of ustekinumab for the treatment of psoriasis in pregnancy to be uncertain (AAD/NPF [Menter 2019]).
Until additional information is available, ustekinumab is not currently recommended for the treatment of rheumatic and musculoskeletal diseases during pregnancy. Ustekinumab should be discontinued once pregnancy is confirmed (ACR [Sammaritano 2020]).
Inflammatory bowel disease is associated with adverse pregnancy outcomes including an increased risk of miscarriage, premature delivery, delivery of a low birth weight infant, and poor maternal weight gain. Management of maternal disease should be optimized prior to pregnancy. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes. Information related to the use of ustekinumab in pregnancy is limited. When treatment for inflammatory bowel disease is needed in pregnant patients, appropriate biologic therapy can be continued without interruption. Serum levels should be evaluated prior to conception and optimized to avoid subtherapeutic concentrations or high levels which may increase placental transfer. Dosing can be adjusted so delivery occurs at the lowest serum concentration. For ustekinumab, the final injection can be given 6 to 10 weeks prior to the estimated date of delivery (4 to 5 weeks before delivery if every-4-week dosing), then continued 48 hours' postpartum (Mahadevan 2019).
Ustekinumab may be present in breast milk (Klenske 2019; Matro 2018).
In a study of six women, four had detectable breast milk concentrations of ustekinumab; maximum concentrations occurred 12 to 24 hours after the infusion (Matro 2018). A case report describes use of ustekinumab 390 mg, reinitiated at 7 weeks' postpartum (last maintenance pregnancy dose of 90 mg every 8 weeks was at 30 weeks' gestation). Four months after postpartum therapy began, maternal trough serum and breast milk concentrations of ustekinumab were 4.6 mcg/mL and 3.2 mcg/mL, respectively. Breast milk concentrations were lower within 1 day after the third maintenance dose (0.82 mcg/mL) and continued to decrease (0.16 mcg/mL 4 weeks later). Adverse events were not observed in the breastfed infant, followed until 12 months of age (Klenske 2019).
Systemic exposure to a breastfed infant is expected to be low secondary to the large size of the molecule and the degradation of ustekinumab within the GI tract. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Treatment with ustekinumab may be continued or initiated in breastfeeding patients with rheumatic and musculoskeletal diseases (ACR [Sammaritano 2020]).
CBC with differential (baseline); complete metabolic panel (baseline); tuberculosis (TB) screening prior to initiating and during therapy (chest X-ray if TB positive); hepatitis C virus/hepatitis B virus (HBV) screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); HIV screening (baseline) (AAD/NPF [Menter 2019]); monitor for signs/symptoms of infection, posterior reversible encephalopathy syndrome, and squamous cell skin carcinoma.
Ustekinumab is a human monoclonal antibody that binds to and interferes with the proinflammatory cytokines, interleukin (IL)-12 and IL-23. Biological effects of IL-12 and IL-23 include natural killer (NK) cell activation, CD4+ T-cell differentiation and activation. Ustekinumab also interferes with the expression of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-inducible protein-10 (IP-10), and interleukin-8 (IL-8). Significant clinical improvement in psoriasis and psoriatic arthritis patients is seen in association with reduction of these proinflammatory signalers.
Onset of action: Psoriasis: Response best determined after 12 weeks (AAD/NPF [Menter 2019]).
Distribution:
Crohn disease: Vd (central compartment): 2.7 L; Vdss: 4.6 L.
Ulcerative colitis: Vd (central compartment): 3 L; Vdss: 4.4 L.
Half-life elimination: SubQ:
Crohn disease, ulcerative colitis: Terminal: ~19 days.
Psoriasis: 14.9 ± 4.6 to 45.6 ± 80.2 days.
Time to peak, plasma: Psoriasis: SubQ: 45 mg: 13.5 days; 90 mg: 7 days.
Body weight: When given the same dose, subjects weighing >100 kg had lower median serum concentrations compared with those subjects weighing ≤100 kg. The median trough serum concentrations of ustekinumab in subjects >100 kg in the 90 mg group were comparable with those in subjects ≤100 kg in the 45 mg group.
Solution (Stelara Intravenous)
130MG/26ML (per mL): $85.57
Solution (Stelara Subcutaneous)
45 mg/0.5 mL (per 0.5 mL): $15,298.27
Solution Prefilled Syringe (Stelara Subcutaneous)
45 mg/0.5 mL (per 0.5 mL): $15,298.27
90 mg/mL (per mL): $30,596.54
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