Ixekizumab

Introduction

In March 2016, the US FDA approved the biological treatment ixekizumab (TALTZ^™ Eli Lilly, Indiana, USA) for the treatment of psoriasis. In November 2017, they also approved it for active psoriatic arthritis.

In April 2016, the European Medicines Agency also granted marketing authorization of ixekizumab for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy.

Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) with neutralizing activity against IL-17A. See Interleukin-17 in inflammatory skin disorders.

It is produced by recombinant DNA technology in a mammalian cell line and is comprised of two identical light chain polypeptides of 219 amino acids each and two identical heavy chain polypeptides of 445 amino acids each.

What is ixekizumab used for?

Ixekizumab is used for treating moderate to severe plaque psoriasis in adult patients that are candidates for systemic therapy (medicine absorbed into the bloodstream) or phototherapy (ultraviolet light treatment). It has also been demonstrated to improve scalp psoriasis and nail psoriasis.

How does ixekizumab work?

• Psoriasis is characterized by inflammation and keratinocyte hyperproliferation thought to be the pathological consequence of a T-cell–mediated immune response to an as-yet-unidentified autoantigen.
• Studies have shown that a subgroup of CD4+ T cells, type 17 helper T (Th17) cells, may play a specific pathological role in psoriasis.
• Type 17 helper T cells secrete a number of proinflammatory cytokines, including interleukin-17A, a member of the proinflammatory interleukin-17 cytokine (messenger protein) family.
• Specific inhibition of interleukin-17A represents a novel, targeted approach to psoriasis treatment.

Dosage and administration

• Ixekizumab is administered by subcutaneous injection, using an auto-injector.
• The recommended dose is 160 mg (two 80-mg injections) at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.
• Ixezinumab is available as a single dose autoinjector and prefilled syringe.
• Patients may self-inject after training in subcutaneous injection technique using the autoinjector or prefilled syringe.
• Each injection is given at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) but not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis.
• A missed dose should be, administered as soon as possible. Thereafter, dosing is resumed at the regularly scheduled time.
• Before injection, remove TALTZ autoinjector or TALTZ prefilled syringe from the refrigerator and allow TALTZ to reach room temperature (30 minutes) without removing the needle cap.
• TALTZ is clear and colourless to a slightly yellow solution and should not be used if the liquid contains visible particles, is discoloured or cloudy.

Link to key clinical-trial evidence about ixekizumab

Potential drug interactions with ixekizumab

• No formal pharmacokinetic drug-drug interaction studies have been conducted with ixekizumab.
• Dosage modification of CYP450 substrates such as warfarin and ciclosporin should be considered when initiating or discontinuing treatment with ixekizumab.

What are the adverse effects of ixekizumab?

Ixekizumab is very well tolerated. Most common (≥ 1%) adverse reactions associated with ixekizumab treatment are:

• Injection site reactions
• Upper respiratory tract infections
• Nausea
• Candida infections
• Tinea infections.

Less common adverse reactions (< 1%) include:

• Rhinitis
• Oral candidiasis
• Urticaria
• Influenza
• Conjunctivitis
• Inflammatory bowel disease
• Angioedema

Warnings and precautions

• Patients should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur.
• Ixekizumab increases the risk of infection and should be discontinued until the infection resolves.
• Patients receiving ixekizumab should be monitored closely for signs and symptoms of active tuberculosis (TB) during and after treatment
• Ixekizumab should not be administered to patients with active TB infection.
• Treatment of latent TB should be initiated prior to treatment with ixekizumab.
• Ixekizumab should be discontinued immediately and appropriate therapy initiated in the event of a serious hypersensitivity reaction such as difficulty in breathing, throat tightness, angioedema or urticaria.
• During clinical trials, Crohn disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the ixekizumab group (Crohn disease 0.1%, ulcerative colitis 0.2%) than in the placebo group (0%).
• Patients should be monitored for the onset or exacerbations of inflammatory bowel disease during treatment with ixekizumab.
• Avoid the use of live vaccines in patients treated with ixekizumab.

Use of ixekizumab in pregnancy

• There are no available data on ixekizumab use in pregnant women.
• Human IgG is known to cross the placental barrier and ixekizumab, which is an IgG4, has the potential to be transmitted from the mother to the developing fetus.
• In animal reproduction studies, administration of ixekizumab to cynomolgus monkeys from the onset of organogenesis through to delivery resulted in premature fetal death.

Use of ixekizumab in nursing mothers

• It is not known whether ixekizumab or its metabolites are present in human milk.
• Women should be advised to discontinue breastfeeding during treatment.

Paediatric use of ixekizumab

The safety and effectiveness of ixekizumab has not been established in paediatric patients (<18 years of age).

Geriatric use of ixekizumab

Clinical studies of ixekizumab did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients.

Renal or hepatic impairment and ixekizumab

No formal studies have been conducted on the effect of hepatic or renal impairment on the pharmacokinetics of ixekizumab.

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

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).