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Author: Anoma Ranaweera, Medical Writer, Auckland, New Zealand. DermNet New Zealand Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. May 2018.
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).
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.
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.
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.
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.
No trials have been conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of tildrakizumab.
The most common adverse reactions reported from tildrakizumab are:
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.
Tildrakizumab is contraindicated in individuals who:
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.
If you are not based in New Zealand, we suggest you refer to your national drug approval agency for further information about medicines (eg, the Australian Therapeutic Goods Administration and the US Food and Drug Administration) or a national or state-approved formulary (eg, the New Zealand Formulary and New Zealand Formulary for Children and the British National Formulary and British National Formulary for Children).
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