for: Plaque Psoriasis
Ilumya (tildrakizumab-asmn) is a humanized, anti-IL-23p19 monoclonal antibody for the treatment of moderate-to-severe plaque psoriasis Strength:
1 INDICATIONS AND USAGE
ILUMYA� is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
2 DOSAGE AND ADMINISTRATION
ILUMYA is administered by subcutaneous injection. The recommended dose is 100 mg at Weeks 0, 4, and every twelve weeks thereafter. Each syringe contains 1 mL of 100 mg/mL tildrakizumab-asmn.
2.2 Tuberculosis Assessment Prior to Initiation of ILUMYA
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with ILUMYA [see Warnings and Precautions (5.3)].
2.3 Important Administration Instructions
ILUMYA should only be administered by a healthcare provider. Administer ILUMYA subcutaneously. Each pre-filled syringe is for single-dose only. Inject the full amount (1 mL), which provides 100 mg of tildrakizumab per syringe. If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regularly scheduled interval.
2.4 Preparation and Administration of ILUMYA
Before injection, remove ILUMYA carton from the refrigerator, and let the prefilled syringe (in the ILUMYA carton with the lid closed) sit at room temperature for 30 minutes.
Follow the instructions on the ILUMYA carton to remove the prefilled syringe correctly, and remove only when ready to inject. Do not pull off the needle cover until you are ready to inject.
Inspect ILUMYA visually for particulate matter and discoloration prior to administration. ILUMYA is a clear to slightly opalescent, colorless to slightly yellow solution. Do not use if the liquid contains visible particles or the syringe is damaged. Air bubbles may be present; there is no need to remove them.
Choose an injection site with clear skin and easy access (such as abdomen, thighs, or upper arm). Do not administer 2 inches around the navel or where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis. Also do not inject into scars, stretch marks, or blood vessels.
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While holding the body of the syringe, pull the needle cover straight off (do not twist) and discard.
Inject ILUMYA subcutaneously as recommended [see Dosage and Administration (2.3)].
Press down the blue plunger until it can go no further. This activates the safety mechanism that will ensure full retraction of the needle after the injection is given.
Remove the needle from the skin entirely before letting go of the blue plunger. After the blue plunger is released, the safely lock will draw the needle inside the needle guard.
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Discard of any unused portion. Dispose of used syringe.
3 DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/mL solution in a single-dose prefilled syringe. ILUMYA is a clear to slightly opalescent, colorless to slightly yellow solution.
ILUMYA is contraindicated in patients with a previous serious hypersensitivity reaction to tildrakizumab or to any of the excipients [see Warnings and Precautions (5.1)].
5 WARNINGS AND PRECAUTIONS
Cases of angioedema and urticaria occurred in ILUMYA treated subjects in clinical trials. If a serious hypersensitivity reaction occurs, discontinue ILUMYA immediately and initiate appropriate therapy [see Adverse Reactions (6.1)].
ILUMYA may increase the risk of infection. Although infections were slightly more common in the ILUMYA group (23%), the difference in frequency of infections between the ILUMYA group and the placebo group was less than 1% during the placebo-controlled period. However, subjects with active infections or a history of recurrent infections were not included in clinical trials. Upper respiratory infections occurred more frequently in the ILUMYA group than in the placebo group [see Adverse Reactions (6.1)].
The rates of serious infections for the ILUMYA group and the placebo group were ≤0.3%. Treatment with ILUMYA 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 ILUMYA. Instruct patients to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, monitor the patient closely and consider discontinuation of ILUMYA until the infection resolves [see Adverse Reactions (6.1)].
5.3 Pretreatment Evaluation for Tuberculosis
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with ILUMYA. Initiate treatment of latent TB prior to administering ILUMYA. In clinical trials, of 55 subjects with latent TB who were concurrently treated with ILUMYA and appropriate TB prophylaxis, no subjects developed active TB (during the mean follow-up of 56.5 weeks). One other subject developed TB while receiving ILUMYA. Monitor patients for signs and symptoms of active TB during and after ILUMYA treatment. Consider anti-TB therapy prior to initiation of ILUMYA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Do not administer ILUMYA to patients with active TB infection.
Prior to initiating therapy with ILUMYA, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid the use of live vaccines in patients treated with ILUMYA. No data are available on the response to live or inactive vaccines.
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
Infections [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials, a total of 1994 subjects with plaque psoriasis were treated with ILUMYA, of which 1083 subjects were treated with ILUMYA 100 mg. Of these, 672 subjects were exposed for at least 12 months, 587 for 18 months, and 469 for 24 months.
Data from three placebo-controlled trials (Trials 1, 2, and 3) in 705 subjects (mean age 46 years, 71% males, 81% white) were pooled to evaluate the safety of ILUMYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 12 weeks [Q12W]) [see Clinical Studies (14)].
Placebo-Controlled Period (Weeks 0-16 of Trial 1 and Weeks 0-12 of Trials 2 and 3)
In the placebo-controlled period of Trials 1, 2, and 3 in the 100 mg group, adverse events occurred in 48.2% of subjects in the ILUMYA group compared to 53.8% of subjects in the placebo group. The rates of serious adverse events were 1.4% in the ILUMYA group and 1.7% in the placebo group.
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the ILUMYA group than in the placebo group.
Table 1:Adverse Reactions Occurring in ≥1% of Subjects in the ILUMYA Group and More Frequently than in the Placebo Group in the Plaque Psoriasis Trials 1, 2, and 3
Upper respiratory infections*
Injection site reactions�
* Upper respiratory infections include nasopharyngitis, upper respiratory tract infection, viral upper respiratory tract infection, and pharyngitis.
� Injection site reactions include injection site urticaria, pruritus, pain, reaction, erythema, inflammation, edema, swelling, bruising, hematoma, and hemorrhage.
During the placebo-controlled period of Trials 1, 2, and 3, adverse reactions that occurred at rates less than 1% but greater than 0.1% in the ILUMYA group and at a higher rate than in the placebo group included dizziness and pain in extremity.
Specific Adverse Reactions
Cases of angioedema and urticaria occurred in ILUMYA-treated subjects in clinical trials [see Warnings and Precautions (5.1)].
Infections were slightly more common in the ILUMYA group. The difference in frequency of infections between the ILUMYA group (23%) and the placebo group was less than 1% during the placebo-controlled period. The most common (≥1%) infections were upper respiratory infections. The rates of severe infections for the ILUMYA group and the placebo group were ≤0.3%.
Safety Through Week 52/64
Through Week 52 (Trials 1 and 3) and Week 64 (Trial 2), no new adverse reactions were identified with ILUMYA use and the frequency of the adverse reactions was similar to that observed during the placebo-controlled period.
As with all therapeutic proteins there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to tildrakizumab in the studies described below with the incidences of antibodies in other studies or to other products may be misleading.
Up to Week 64, approximately 6.5% of subjects treated with ILUMYA 100 mg developed antibodies to tildrakizumab. Of the subjects who developed antibodies to tildrakizumab, approximately 40% (2.5% of all subjects receiving ILUMYA) had antibodies that were classified as neutralizing. Development of neutralizing antibodies to tildrakizumab was associated with lower serum tildrakizumab concentrations and reduced efficacy.
7 DRUG INTERACTIONS
7.1 Live Vaccinations
Avoid use of live vaccines in patients treated with ILUMYA [see Warnings and Precautions (5.4)].
8 USE IN SPECIFIC POPULATIONS
Limited available data with ILUMYA use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. Human IgG is known to cross the placental barrier; therefore, ILUMYA may be transferred from the mother to the fetus. An embryofetal developmental study conducted with tildrakizumab in pregnant monkeys revealed no treatment-related effects to the developing fetus when tildrakizumab was administered subcutaneously during organogenesis to near parturition at doses up to 159 times the maximum recommended human dose (MRHD). When dosing was continued until parturition, a small increase in neonatal death was observed at 59 times the MRHD [see Data].The clinical significance of this nonclinical finding is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
In an embryofetal developmental study, subcutaneous doses up to 300 mg/kg tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks during organogenesis to gestation day 118 (22 days from parturition). No maternal or embryofetal toxicities were observed at doses up to 300 mg/kg (159 times the MRHD of 100 mg, based on AUC comparison). Tildrakizumab crossed the placenta in monkeys.
In a pre- and postnatal developmental study, subcutaneous doses up to 100 mg/kg tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks from gestation day 50 to parturition. Neonatal deaths occurred in the offspring of one control monkey, two monkeys at 10 mg/kg dose (6 times the MRHD based on AUC comparison), and four monkeys at 100 mg/kg dose (59 times the MRHD based on AUC comparison). The clinical significance of these nonclinical findings is unknown. No tildrakizumab-related adverse effects were noted in the remaining infants from birth through 6 months of age.
There are no data on the presence of tildrakizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk. Tildrakizumab was detected in the milk of monkeys [see Data].
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ILUMYA and any potential adverse effects on the breastfed child from ILUMYA or from the underlying maternal condition.
Very low levels of tildrakizumab were detected in breast milk of monkeys in the pre- and postnatal developmental study described in 8.1. The mean tildrakizumab concentrations in milk were approximately 0.09 � 0.2% of that in serum on postpartum days 28 and 91.
8.4 Pediatric Use
Safety and effectiveness of ILUMYA in pediatric patients (<18 years of age) have not been established.
8.5 Geriatric Use
A total of 1083 subjects were exposed to ILUMYA 100 mg during Phase 2 and 3 trials. A total of 92 subjects were 65 years or older, and 17 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects [see Clinical Pharmacology (12.3)].
In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and administer appropriate symptomatic treatment immediately.