Background

Psoriasis is an immune-mediated chronic inflammatory disease that affects the skin and/or joints of a person. Although the exact cause of psoriasis has not been determined, it is thought to be caused by a combination of genetic and environmental factors. Environmental factors, including stress, injury and infections, trigger an inflammatory immune response involving dendritic cells, T cells, keratinocytes, neutrophils and cytokines in those predisposed to the disease.1 The prevalence of the disease ranges from 0.91% in the United States to 8.5% in Norway.

There are several types of psoriasis, including plaque, pustular, inverse and erythrodermic, with plaque psoriasis the most common, affecting 90% of sufferers.2 The signs and symptoms of this type of psoriasis include raised erythematous and well-demarked areas of inflamed skin, covered by silvery white, scaly skin, typically located on the elbows, knees, scalp, lower back and periumbilical region.2,3 The severity of symptoms varies, ranging from exacerbations of the disease that can involve the whole body, to minor localized patches of inflammation and remission.4 A psychological impact has also been reported, with impairment of quality of life and stigma associated with symptomology.5

No cure exists for psoriasis and treatment involves symptom management. Treatment regimes are, typically long term in nature and involve two discrete phases: induction therapy, leading to short-term remission and maintenance therapy, leading to long-term remission. Topical agents are the first line of treatment; however in moderate-to-severe cases a second-line therapy may be required, for example phototherapy and the use of conventional systemic agents such as cyclosporine or methotrexate. Progress in physiological comprehension led to the emergence of biologic treatments and offered new therapeutic possibilities for patients. Biologic treatments work by suppressing the immune system.

Objective/s

The primary objective of this review was to compare the efficacy and safety of conventional systemic agents, small molecules and biologics in the treatment of moderate-to-severe psoriasis.6 The results would then be used to rank these treatments according to efficacy and safety.

Intervention/methods

The review included randomized controlled trials that included adults over the age of 18, clinically diagnosed with moderate-to-severe plaque psoriasis.

The interventions involved the use of systemic and biologic treatments, irrespective of dose and duration, compared with placebo or each other.

The primary outcomes included:

1. The proportion of participants who achieved clear or almost clear skin, according to the Psoriasis Area and Severity Index (PASI 90);

2. Serious adverse effects (SAE).

Secondary outcome measures considered were:

1. Proportion of participants who achieved clear or almost clear skin (PASI of 75) at induction phase:

2. Proportion of participants who achieved a Physicians Global Assessment value of 0 or 1;

3. Quality of life;

4. Adverse effects;

5. Relapses in maintenance phase (between 52 and 104 weeks).

Outcomes were evaluated for two discrete durations of therapy, induction therapy and maintenance therapy.

Results

There were 109 studies included in this review, representing a total of 39 882 participants, 68% of whom were male. All studies utilized a parallel group design. Over two-thirds of the studies compared an intervention to a placebo (n = 73) with 25 head to head and 11 multiarmed studies. A total of 74 studies (n = 35 454 participants) were included in the network meta-analysis for at least one of the outcomes.

All interventions were found to be superior to placebo in treating psoriasis with induction therapy (evaluation between weeks 12 and 16), based on PASI score of 90. At class level, the biologic agents, specifically anti-IL17, anti-IL12/23, anti-IL23 and anti-TNF alpha, were found to be the most effective treatments followed by small molecules and conventional systemic agents.

In terms of individual drugs, the biologic agent ixekizumab was identified as the most effective medication for reaching PASI 90, based on high-certainty evidence. Other drugs of significance (in order of efficacy) were secukinumab (high-certainty evidence), brodalumab, guselkumab and certolizumab (all moderate-certainty evidence) and ustekinumab (high-certainty evidence). The authors noted that the results were very similar for the outcome measure PASI 75.

No significant differences were identified between any interventions compared with placebo for the risk of SAE, with the drug methotrexate reported to have the best safety profile. When both efficacy (PASI 90 outcome) and acceptability (SAE outcome) were considered, it was noted that highly effective treatments had more SAEs than other treatments. Based on this information the drugs ustekinumab, infliximab and certolizumab were identified as the best compromise between effectiveness and side effects.

Conclusion

Biologic agents were found to be the most effective class of drug in the treatment of plaque psoriasis. The authors identified and ranked six individual drugs based on their efficacy in the treatment of those with moderate-to-severe psoriasis, based on moderate-to-high certainty evidence: these were ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab and ustekinumab. The authors noted that results were based only on induction therapy, and that information on long-term efficacy, critical given the chronic nature of the disease, and safety data were lacking.

Implications for practice

Plaque psoriasis is a chronic disease that leads to periods of remission and exacerbation of symptoms in patients. As there is no cure for psoriasis, treatment is aimed at symptom management, at alleviating symptoms during flare-ups as well as increasing the length of periods of remission. The current guidelines for pharmacological treatment are lacking and conventional systemic agents were not found to be the most effective treatments in this review. Nurses should ensure that they consider the psychological impact of the disease on their patients, to ensure that their quality of life is not negatively impacted.

Acknowledgements

Conflicts of interest

The author reports no conflicts of interest.

References