In March 2018, the biological treatment tildrakizumab (Ilumya™; Sun Pharma India) received US Food and Drug Administration (FDA) approval for the treatment of moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy. Sun Pharma licensed the monoclonal antibody (a biological drug), which selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor, from Merck and Co. (New Jersey, USA) in 2014.
FDA approval was based on safety and efficacy data from the reSURFACE Phase III clinical trials, which linked tildrakizumab to significant improvements in both Psoriasis Area and Severity Index (PASI) score and Physician’s Global Assessment (PGA) at Week 12, compared with placebo.
See our page on key clinical-trial evidence for tildrakizumab.
Almirall has been granted rights to develop and commercialise the drug in Europe. An application seeking approval of the drug in Europe is currently under review by the European Medicines Agency. Tildrakizumab is not currently available in New Zealand (2018).
How does tildrakizumab work?
Tildrakizumab is a human monoclonal immunoglobulin G1 lambda (IgG1λ) antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor.
IL-23 promotes normal inflammatory and immune responses. Psoriasis and other autoimmune inflammatory skin diseases are the result of the overexpression of the p19 and p40 subunits of IL-23. Tildrakizumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes, blocking its interaction with IL-23 receptors and preventing the release of pro-inflammatory cytokines and chemokines.
Tildrakizumab thus blocks the abnormally-heightened signalling of inflammatory cascades (the chain reaction effect that initiates the inflammatory response) that promote hyperproliferation (high rates of cell division) of keratinocytes and the formation of psoriatic plaques.
How is tildrakizumab given?
Tildrakizumab should be administered by subcutaneous injection under the guidance and supervision of a physician. The recommended dose is 100 mg at Week 0 and Week 4, and every 12 weeks thereafter.
Treatment with tildrakizumab should not be started in patients with any clinically important active infection until the infection resolves or is adequately treated. A missed dose should be injected as soon as it is remembered, and the next dose should be taken at the appropriate scheduled time.
Tildrakizumab should not be injected into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis, as it may increase the risk of infection.
Pre-treatment evaluation for tuberculosis and immunisation
Patients who are being assessed for treatment with tildrakizumab should undergo tuberculosis screening and their vaccination status should be reviewed. See our page on immunisation in immunosuppressed dermatology patients.
- Patients whose tuberculosis screening is positive or who have a history of latent tuberculosis should be suitably treated prior to the administration of tildrakizumab, because the drug can reactivate tuberculosis.
- Patients should not be immunised with live vaccines during treatment with tildrakizumab.
The use of tildrakizumab in specific populations
- The limited data available for the use of tildrakizumab in pregnant women do not indicate a drug-associated risk for major birth defects and miscarriage.
- Human IgG is known to cross the placental barrier; therefore, tildrakizumab may be transferred from the mother to the fetus.
- An embryo-fetal developmental study conducted with tildrakizumab in pregnant monkeys revealed no treatment-related effects to the developing fetus when tildrakizumab was administered subcutaneously during organogenesis (organ development) to near parturition (childbirth) at doses up to 159 times the maximum recommended human dose.
- See our pages on the safety of medicines taken during pregnancy and on biologics and novel small molecule treatments, reproduction and psoriasis.
- There is no information on the presence of tildrakizumab in human milk or its effects on the breastfed infant.
- The risk–benefit potential should be considered when prescribing tildrakizumab to the mother.
- See our page on lactation and medications used in dermatology.
The safety and effectiveness of tildrakizumab in children under 18 years of age have not been evaluated.
Clinical studies with tildrakizumab did not include sufficient numbers of individuals aged 65 years and over to determine whether they respond differently from younger subjects.
Patients with hepatic or renal impairment
No trials have been conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of tildrakizumab.
What are the risks with tildrakizumab?
Adverse events with tildrakizumab
The most common adverse reactions reported from tildrakizumab are:
- Upper respiratory infections (in >10% of patients)
- Injection site reactions (3%)
- Diarrhoea (2%).
What are the adverse drug interactions of tildrakizumab?
Cytochrome P450 (CYP) substrates
In subjects with plaque psoriasis, the area under the concetration-time curve (AUC∞) of dextromethorphan (CYP2D6 substrate) increased by 20% when used concomitantly with tildrakizumab 200 mg (twice the approved recommended dose).
No clinically significant changes in AUC∞ have been noted with caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), or midazolam (CYP3A4 substrate) when given at the same time as tildrakizumab.
No data are available on the ability of live or inactive vaccines to elicit an immune response in patients receiving treatment with tildrakizumab. Live vaccines should not be used concomitantly during treatment with tildrakizumab.
Contraindications to tildrakizumab
Tildrakizumab is contraindicated in individuals who:
- Have previous serious hypersensitivity reactions to tildrakizumab or to any of the excipients in the product
- Have an currently persisting or recurring infection
- Have tuberculosis or have been in close contact with someone with tuberculosis
- Recently received, or are scheduled to receive, a vaccine
- Plan to become pregnant
- Are currently breastfeeding or plan to breastfeed.
What is the outlook for treatment with tildrakizumab?
Selective neutralisation of IL-23 is an advantageous strategy for treating psoriasis. Preliminary data from Phase II and III trials have shown the capability of this therapeutic class in inducing complete clearance or almost complete clearance of psoriasis in many patients.
Given the therapeutic target, an extended subcutaneous administration schedule of 12 weeks, and a safety and efficacy profile comparable to ustekinumab, it is anticipated that tildrakizumab can be placed alongside guselkumab as a preferential treatment for psoriasis.
Tildrakizumab’s 12-week administration period may be more convenient than the 8-week maintenance schedule of guselkumab.
There are so far no direct comparison studies between tildrakizumab and guselkumab.
Based on the results to date, tildrakizumab appears to be a promising therapeutic option for moderate to severe plaque-type psoriasis, although further studies are needed to assess its long-term safety and efficacy.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).