Mia's treatment

In the video below, Professor Matthias Augustin explains some of major differences between treating young children and adolescents with psoriasis.

Topical treatments

So when topical agents are not enough, what comes next?

A retrospective study at 20 centres in North America and Europe assessed patterns of use for moderate-to-severe psoriasis in children over a 25-year period⁶ (Figure 1).

Figure 1. Percentages of children (n = 390) with moderate-to-severe psoriasis treated with systemic therapies (adapted from Bronckers et al.⁶ ). * Primarily etanercept

Let’s find out more about these treatments next.

Systemic treatments

In general, the goal with all systemic therapy use in children is to²:

• Control or clear the disease
• Maintain stability for several months
• Taper to the lowest effective dose
• Transition off or maintain at the lowest effective dose with the least toxic therapy

While no systemic treatments are specifically approved for children with moderate-to-severe psoriasis, a number are in routine use and have sufficient evidence to be recommended by paediatric guidelines². These treatments require regular monitoring (Figure 2).

Figure 2. Suggested monitoring for systemic paediatric psoriasis medications (adapted from Menter et al.²; van Geel et al.⁷; SmPC⁸). For all paediatric patients receiving long-term systemic therapy, growth parameters should also be monitored.
BUN, Blood urea nitrogen; CBC, complete blood count; diff, differential; LFT, liver function test; PPD, protein derivative test; TB, tuberculosis

Let’s now take a look at the efficacy data for these systemic treatments in children. Methotrexate has been evaluated relative to acitretin and ciclosporin (Figure 3).

Figure 3. Comparative study of systemic treatments for childhood psoriasis (adapted from Ergun et al.⁹). PASI, Psoriasis area and severity index

No treatment was found to be superior to another but it was noted that there were high rates of secondary loss of response (up to 16.5% of patients) which highlights the importance of assessing long-term efficacy⁹.

While there is limited data with fumaric acid esters (FAE) in children, a retrospective case series of 14 children treated with FAE showed >PASI 80 in 36% of patients¹⁰.

Regarding safety, a multicentre retrospective chart review of patients with childhood psoriasis which included a cohort of 19 patients treated with fumaric acid esters showed that thirteen (68%) of the patients developed adverse events which led to treatment discontinuation (including abdominal pain, diarrhoea, flushing and headache) with two patients (10%) discontinuing therapy because of serious adverse events (pericarditis and bone marrow suppression)¹¹. This suggests that adverse event rates are higher for fumaric acid esters relative to other systemic therapies despite shorter treatment durations².

Professor Paller comments on the effectiveness of phototherapy or methotrexate for paediatric patients and the safety concerns to address with parents of children with psoriasis.

Biologic treatments

Biologic therapies for moderate-to-severe psoriasis appear to be equally as effective in children as adults with a better safety profile and offer significant increases in quality of life for many patients. At least 25% of patients are now treated with biologics, especially tumour necrosis factor-α (TNFα) inhibitors and their use is expanding with increasing efficacy and safety data, availability, and physician experience¹².

Is it important to educate on new treatments for paediatric psoriasis? Professor Matthias Augustin, Director of the Institute for Health Services Research in Dermatology and Nursing, in Hamburg, Germany, speaks to the importance of educating healthcare professionals and parents on emerging treatments for paediatric psoriasis.

We asked Professor Torres his view on the use of anti-TNFs and if that was likely to change in the future.

There are differences in the approval status and indication for paediatric psoriasis biologic treatments in the US and Europe. Figures 4 and 5 give the details for each region, along with contraindications and side effects.

Figure 4. Biologics approved by the EMA for use in paediatric patients (adapted from Paller et al.¹³; SmPC^{14,15,16,17,18}; Landells et al.¹⁹; Thaci et al.²⁰). 

Figure 5. Biologics approved by the FDA for use in paediatric patients (adapted from Paller et al.¹³; Enbrel Prescribing Information^21,22,23; Landells et al.¹⁹; Paller et al.²⁴; Philipp et al.²⁵).

Professor Paller gave us her view on the safety profile of biologics over systemic agents.

Parents may be concerned about the use of biologics in their children while they are developing. We asked Professor Torres his view on any potential effects on growth, the immune system and fertility.

Let’s now take a look at the efficacy data for these biologics in children.

Secukinumab

The IL-17A inhibitor secukinumab has already been shown to be effective and safe in adults. In 2020 secukinumab gained European approval for the treatment of moderate-to-severe plaque psoriasis in children and adolescents following two international Phase III studies^18,26,27.

Table 1: Key efficacy outcomes for secukinumab in paediatric severe chronic Phase III studies (adapted from Bodemer et al²⁶). ^*Patients were stratified and randomised by weight and age to receive low-dose (LD; 75-150 mg) or high-dose (HD; 75-300 mg) secukinumab. CDLQI, Children’s dermatology life quality index; PASI, Psoriasis area and severity index; IGA mod 2011, Investigator’s global assessment modified 2011.

Table 2: Key efficacy outcomes for secukinumab in paediatric moderate-to-severe plaque psoriasis Phase III studies (adapted from Magnolo et al.²⁸). CDLQI, Children’s dermatology life quality index; PASI, Psoriasis area and severity index; IGA mod 2011, Investigator’s global assessment modified 2011.

Professor Matthias Augustin describes the results of his clinical trial investigations on secukinumab.

Etanercept

Table 3. Key efficacy outcomes for etanercept in paediatric Phase III studies (Adapted from Paller et al.^13,29). CDLQI, Children’s dermatology life quality index; P, Probability; PASI, Psoriasis area and severity index; PGA, Physician’s global assessment

Etanercept is approved for use in children in the US from 4 years²¹ and Europe from 6 years¹⁴.

Adalimumab

Table 4. Key efficacy outcomes for adalimumab in paediatric Phase III studies (Adapted from Thaci et al.²⁰). CDLQI, Children’s dermatology life quality index; NS, Not significant; P, Probability; PASI, Psoriasis area and severity index; PGA, Physician’s global assessment

Adalimumab is approved for use in children from 4 years in Europe¹⁵.

Ustekinumab

Table 5. Key efficacy outcomes for ustekinumab in paediatric Phase III studies (Adapted from Landells et al.¹⁹; Philipp et al.²⁵). CDLQI, Children’s dermatology life quality index; P, Probability; PASI, Psoriasis area and severity index; PGA, Physician’s global assessment

Ustekinumab is approved for use in children from 6 years in Europe¹⁶ and adolescents from 12 years in the US²².

Ixekizumab

Table 6. Key efficacy outcomes for ixekizumab in paediatric Phase III studies (Adapted from Paller et al.²⁴). CDLQI, Children’s dermatology life quality index; NS, Not significant; P, Probability; PASI, Psoriasis area and severity index; sPGA, static physician’s global assessment

Ixekizumab is approved for use in children from 6 years in the US and Europe^23,17.

Can the approved biologic treatments achieve complete skin clearance? We asked Professor Matthias Augustin to summarise current data.

What three factors are relevant when selecting a first-line biologic for paediatric psoriasis? Matthias Augustin gives his answer.

COVID-19

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) declared a pandemic by the World Health Organization on 11 March, 2020³⁰. In most cases SARS-CoV-2 infection is cleared by the primary immune response, however in a subgroup of patients the secondary immune response is exaggerated leading to inflammatory lung injury and other complications which can lead to death³¹. Several cutaneous immune-mediated diseases, including psoriasis, are treated with systemic and biologic immunosuppressive and immunomodulatory drugs and so both physicians and patients are concerned about how COVID-19 affects the management of psoriasis.

Find out the SARS-CoV-2 pandemic is affecting treatment and clinical research into childhood psoriasis from Professor Paller.

Efficacy and drug survival vs methotrexate

Hear Professor Tiago Torres describing a real world efficacy study in this short video clip.

The efficacy data here for biologics is similar to that achieved in the Phase III clinical trials. Drug survival is a factor of the rate and duration of adherence to a specific drug (Figure 6).

Figure 6. Drug survival of methotrexate and biologic agents in childhood psoriasis (adapted from Bronckers et al.³³).

Consistent with the efficacy results, biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR] 2.23; 95% CI 1.21–4.10; P=0.01). Interestingly, discontinuation owing to lack of response was comparable (HR 1.64; 95% CI 0.80–3.36; P=0.18)³³.

Quality of life

Only one randomised clinical trial has previously tested whether the degree of psoriasis area and severity index (PASI) response is associated with improvement in quality of life (QoL). In 106 children treated with etanercept a PASI 75 score at Week 12 correlated with improved QoL as measured by the Children’s Dermatology Life Quality Index (CDLQI)³⁴.

A 2020 prospective single-centre study conducted in the Netherlands over 10 years has since evaluated the association between degree of psoriasis improvement and QoL in 319 paediatric patients with 556 treatment episodes³².

The greatest improvements in CDLQI scores were seen in the PASI 90 and BSA 90 response categories, with an estimated marginal mean change in CDLQI score of −6.6 (95% CI, –7.5 to –5.7). This was achieved in patients treated with either systemic or biologic agents and supports that reaching PASI 90 or greater and decreasing BSA involvement by at least 90% may be clinically meaningful treatment goals³².

Both clinical trial and real world data show that systemic and biologic therapies offer both symptom control and improved quality of life. However, all these studies show a proportion of patients who do not achieve complete skin clearance or an effectively ‘normal’ QoL.

Unfortunately this is the case for our patient Mia who has tried many treatments over the past six years.