Clinical Overview: Tildrakizumab-asmn (Ilumya) for Plaque Psoriasis

Tildrakizumab-asmn is a humanized IgG1/k monoclonal anti-IL-23 antibody indicated for the treatment of adults with moderate-to-severe plaque psoriasis.

Tildrakizumab-asmn (Ilumya) is an interleukin-23 (IL-23) antagonist. The FDA approved the treatment in 2018 for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy based on the data from 2 randomized phase 3 trials (reSURFACE 1 and reSURFACE 2).1

In these 2 trials, 926 enrolled patients received either 100 mg tildrakizumab-asmn (n=616) or placebo (n=310) with the co-primary endpoints of proportion of patients achieving Psoriasis Area Sensitivity Index 75% (PASI 75) and Physician's Global Assessment (PGA) response of clear or minimal with at least a 2-grade reduction from baseline at week 12 after 2 doses. Both studies met the primary efficacy endpoints by showing the significant clinical improvement of 100 mg tildrakizumab-asmn compared to the placebo group on the above measurements. The results are shown below in Table 1.1

Table 1. Primary efficacy endpoint from 2 phase 3 trials at week 121

After the FDA approval, the researchers continued the extension studies from those 2 trials to evaluate the 5-year efficacy and safety of tildrakizumab-asmn in patients with moderate-to-severe psoriasis. The pooled analysis from the phase 3 trials showed nearly 9 of 10 patients treated with tildrakizumab-asmn 100 mg maintained their responses through year 5 and that this dosage level was well-tolerated during the trials.2,3

Mechanism of Action4

Tildrakizumab-asmn is a humanized IgG1/k monoclonal anti-IL-23 antibody. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Tildrakizumab-asmn selectively binds to the p19 subunit of IL-23 to inhibit its interaction with the IL-23 receptor and downstream signaling to block the release of pro-inflammatory cytokines and chemokines.

Dosage and Administration4

The recommended dose is 100 mg at weeks 0, 4, and every 12 weeks thereafter. Each pre-filled syringe contains 1 mL of 100 mg/mL tildrakizumab-asmn. If patients miss a dose, clinicians should administer the dose as soon as possible and then resume dosing at the regularly scheduled interval.

Clinicians should administer tildrakizumab-asmn subcutaneously in areas with clear skin and easy access such as the abdomen, thighs, or upper arms. They should avoid the areas 2 inches around the navel or where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis. They must avoid injecting into scars, stretch marks, or blood vessels.

Tildrakizumab-asmn is a clear to slightly opalescent, colorless to slightly yellow solution. The clinician who administers the dose should inspect visually for precipitation and discoloration prior to administration. If the liquid contains visible particles or the syringe is damaged, clinicians should discard the dose. Air bubbles may be present and need to be removed.

Adverse Events4

The most common (≥1%) adverse reactions are upper respiratory infections, injection site reactions, and diarrhea.

Warning and Precautions4

Hypersensitivity cases, such as angioedema and urticaria, occurred during clinical trials in patients administered tildrakizumab-asmn. If patients experience serious hypersensitivity reactions, the prescriber should stop the medication and initiate the appropriate treatment immediately.

Tildrakizumab-asmn may increase the risk of infection. Patients with any clinically important active infection should not take tildrakizumab-asmn until the infection resolves or is appropriately treated.

Health care providers (HCPs) should consider the risks and benefits before initiating the treatment on patients with a chronic infection or a history of recurrent infection. Instruct patients to consult with an HCP when experiencing signs or symptoms of clinically important chronic or acute infection.

Clinicians should monitor patients closely and discontinue treatment if necessary until the infection resolves. In clinical trials, 23% of patients treated with tildrakizumab-asmn developed infections; however, the different frequency of infections was <1% compared to the placebo group during the placebo-controlled period.

In addition, the tildrakizumab-asmn group had more upper respiratory infections than placebo. The rates of serious infections for the tildrakizumab-asmn group and the placebo group were ≤0.3%.

Tuberculosis (TB) evaluation and treatment for latent TB should be done prior to initiating the tildrakizumab-asmn regime. Prescribers should consider anti-TB therapy before starting tildrakizumab-asmn treatment for patients with past history of latent or active TB but without confirmation of an adequate treatment.

HCPs should monitor the signs or symptoms of active TB during and after tildrakizumab-asmn treatment. Do not administer tildrakizumab-asmn to patients with active TB. During clinical trials, 55 patients were under preventive treatment for TB while receiving tildrakizumab-asmn, but none of them developed active TB during the mean follow-up of 56.5 weeks. The only individuals in the trials who developed active TB were not from this group of 55 patients.

Consider completing all age-appropriate vaccinations before initiating tildrakizumab-asmn treatment. Patients undergoing treatment with tildrakizumab-asmn should avoid live vaccines, although there were no data available on the response to live or inactive vaccines.

Pregnancy and Lactation4

Researchers have insufficient human data on the use of tildrakizumab-asmn during pregnancy and on the presence of tildrakizumab-asmn in human milk, the effects on the breastfed infant, or the effects on milk production to make a recommendation.

About the Author

Marlene Wang, MS, is a research scientist in the pharmaceutical industry.

References

  1. Sun Pharma Announces U.S. FDA Approval of ILUMYA™ (tildrakizumab-asmn) for the Treatment of Moderate-to-Severe Plaque Psoriasis. Sun Pharmaceutical Industries Ltd. Accessed May 26, 2022. https://sunpharma.com/wp-content/uploads/2020/12/Sun-Pharma-Announces-U.S.-FDA-Approval-of-ILUMYA.pdf
  2. Thaci D, Piaserico S, Warren RB, et al. Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2). Br J Dermatol. 2021;185(2):323-334. doi:10.1111/bjd.19866
  3. Sun Pharma’s PrILUMYA™ (tildrakizumab injection) now available to help Canadians living with moderate-tosevere plaque psoriasis.Sun Pharmaceutical Industries Ltd. Accessed May 26, 2022. https://sunpharma.com/wp-content/uploads/2021/10/Press-Release-ILUMYA-availability-in-Canada.pdf
  4. ILUMYA [product information]. Cranbury NJ: Sun Pharmaceutical Industries Ltd; September 2019. Accessed May 26, 2022.