New treatments for psoriasis

Treatment options for psoriasis have expanded rapidly in recent years and several new drugs have been licensed in the UK. This is good news for the 2.8% of the UK population who have this chronic and often distressing condition.¹

NICE guidance recommends treating mild psoriasis with topical therapies, progressing to phototherapy and systemic treatment for moderate disease, and biological therapies for the most severely affected patients.² This article will consider new treatment options and potential side effects for primary care professionals to be aware of.

Topical treatment

Calcipotriene and betamethasone dipropionate (Enstilar®) foam was introduced in the UK in June 2016. This combination foam gives an alternative option to the gel and ointment formulations available. There is evidence that it has greater bio-availability than the ointment, and patients tend to favour the foam formulation for ease of use.³

Studies comparing calcipotriene and betamethasone dipropionate foam to ointment and placebo were favourable.^4-6 Psoriasis Assessment of Severity Index (PASI) scores showed greater improvement for scalp psoriasis at four weeks compared with the ointment, and at eight weeks compared with the gel formulation.

The side effect profile of calcipotriene and betamethasone dipropionate foam is similar to that of other vitamin D/steroid combinations and included itching, erythema and pain at application sites. The treatment can be applied to up to 30% of the body surface area on the trunk and limbs for up to four weeks.

Systemic treatment

Apremilast (Otezla®) is a new option in the systemic pathway. It is a phosphodiesterase type 4 inhibitor (PDE4) that works intracellularly by increasing cyclic adenosine monophosphate (cAMP) levels and subsequently suppressing interleukin-17 (IL17) and IL23. Both of these mediators appear to play a pivotal role in psoriasis pathogenesis.

Apremilast is licensed for the treatment of both chronic plaque psoriasis and psoriatic arthritis. NICE recommendations for use are summarised in box 1.⁷

Apremilast was compared with a placebo in two multicentre trials of 1,257 patients. At 16 weeks, around one third of patients achieved PASI 75, with around half having reached PASI 50. The trials also showed significant improvements in scalp and nail psoriasis, which can be relatively resistant to treatment.

Apremilast has relatively few contraindications (it is not contraindicated in tuberculosis or malignancy) and does not require extensive baseline investigations or regular monitoring. In addition, oral therapy may be preferable to injectable therapy for some patients.

However, tolerability may be an issue. Gastrointestinal side effects, including nausea and diarrhoea, may occur in a significant number of patients. This is usually worst in the first two weeks of treatment, but tends to settle by week four. The dose is titrated over the first five days to help minimise this side effect. Other side effects include headaches and weight loss (although the latter was not clinically relevant in the trial population).

Some patients with psychiatric disease including depression and suicidal ideation may experience worsening of their symptoms during therapy, in which case treatment should be discontinued. The overall rate of withdrawal was found to be 19.5% per annum and comparable to biologics. As with any new drug, long term follow-up data is not available, and trial data is given for 52 weeks only.

NICE have positioned apremilast after conventional systemics and phototherapy as an alternative to biologics.

Biological therapy

Ixekizumab is the latest addition to the biologics family, having recently been approved by NICE for use in moderate to severe psoriasis.⁸ It is the second drug to target IL17a, which has been implicated in the pathogenesis of psoriasis. In common with other biologic therapies, ixekizumab is recommended as an option for treating plaque psoriasis in adults when the following conditions are fulfilled:

• The disease is severe, as defined by a total PASI score of ≥ 10, and DLQI > 10
• The disease has not responded to standard systemic therapies, or these treatments are contraindicated or not tolerated.
• The company provides the drug with the discount agreed in the patient access scheme.

Ixekizumab treatment should be stopped at 12 weeks if the psoriasis has not responded adequately. An adequate response is defined as:

• a 75% reduction in the PASI score (PASI 75) from when treatment started or
• a 50% reduction in the PASI score (PASI 50) and a 5-point reduction in DLQI from when treatment started.

Ixekizumab is given by subcutaneous injection, which patients can self-administer after appropriate training. Initially the drug is given every two weeks for 12 weeks, and then reduced to every four weeks. Dose reductions are not required in elderly patients, or in patients with hepatic or renal impairment. In clinical trials, response was rapid, with clinically relevant improvement noted as early as two weeks in many patients.

Ixekizumab was generally found to be well tolerated, with the most common adverse reactions being upper respiratory tract infections and injection site reactions. As IL17 is integral in fighting bacterial and fungal infections, it is important that serious infections are treated prior to initiation, in particular TB, and that live vaccines are avoided. A further caution is inflammatory bowel disease, because exacerbations and new cases have been reported during treatment.

NICE considered the evidence from the UNCOVER trials and concluded that ixekizumab was more effective than etanercept. In addition, meta-analysis data suggested it was also more efficacious than adalimumab and ustekinumab, with a similar efficacy to its fellow IL17a inhibitor, secukinumab.⁸ However, dermatologists will need to balance this information against the clinical experience with the older drugs, and the longer-term safety data available. It is therefore unlikely that ixekizumab will be widely used as a first line biologic in the near future, but will be an option for when the more established drugs are ineffective, contraindicated or not tolerated.

• Dr Elizabeth Roberts is a Clinical fellow in dermatology in Nottingham
• Dr Shanti Ayob is a Consultant dermatologist in Nottingham

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References

1. Springate DA, Parisi R, Kontopantelis E et al. Incidence, prevalence and mortality of patients with psoriasis: a U.K population- based cohort study. British Journal of Dermatology 2017;176:650-8.
2. NICE. Psoriasis: assessment and management. CG153. October 2012.
3. Lind M, Nielsen KT, Schefe LH et al. Supersaturation of calcipotriene and betamethasone dipropionate in a novel aerosol foam formulation for topical treatment of psoriasis provides enhanced bioavailability of the active ingredients. Dermatol Ther (Heidelb) 2016;6:413–25.
4. Leonardi C, Bagel J, Yamauchi P et al. Efficacy and safety of calcipotriene plus betamethasone dipropionate aerosol foam in patients with psoriasis vulgaris – a randomized phase III study (PSO- FAST). J Drugs Dermatol 2015;14:1468–77.
5. Koo J, Tyring S, Werschler WP et al. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris – A randomized phase II study. J Dermatolog Treat 2016;27:120–7.
6. Paul C, Stein Gold L, Cambazard F et al. Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO-ABLE study. J Eur Acad Dermatol Venereol 2016. doi: 10.1111/jdv.13859.
7. NICE. Apremilast for treating moderate to severe plaque psoriasis. Technology appraisal guidance [TA419] 23 November 2016
8. NICE. Ixekizumab for treating moderate to severe plaque psoriasis. Technology appraisal guidance [TA442] 26 April 2017