Persistence and Effectiveness of Nonbiologic Systemic Therapies for Moderate-to-Severe Psoriasis in Adults

A Systematic Review

K.J. Mason; S. Williams; Z.Z.N. Yiu; K. McElhone; D.M. Ashcroft; C.E. Kleyn; Z.K. Jabbar-Lopez; C.M. Owen; N.J. Reynolds; C.H. Smith; N. Wilson; R.B. Warren; C.E.M. Griffiths


The British Journal of Dermatology. 2019;181(2):256-264. 

In This Article

Materials and Methods

Literature Search

A literature search was completed utilizing Embase, MEDLINE, PubMed and the Cochrane Library. Searches were limited to humans and publications dated from 1 January 2007 to 1 November 2017 to account for research published within the past decade, as the introduction of biologic therapies has influenced systemic treatment prescribing. The full search strategy and complete study protocol are listed in Appendix S1 (see Supporting Information).

Inclusion Criteria

Longitudinal observational studies were eligible for review, including retrospective and prospective cohort studies. Study populations were to include ≥ 100 patients; age > 18 years; diagnosis of moderate-to-severe psoriasis; treatment with acitretin, ciclosporin, FAE or methotrexate; and follow-up time ≥ 3 months. A recent systematic review of observational studies in patients with psoriasis specified a minimum of 100 patients prescribed each therapy to increase statistical power, therefore the same requirement was applied in this review.[11]

Disease severity was ascertained through the inclusion criteria for each study (e.g. patients with moderate-to-severe psoriasis) or baseline measures of severity indicating moderate-to-severe diagnoses, namely Psoriasis Area and Severity Index (PASI) >10, involved body surface area > 10% and/or Dermatology Life Quality Index (DLQI) >10. Studies where > 50% of patients were diagnosed with psoriatic arthritis were excluded, as were studies with pooled cohorts of patients receiving systemic therapies. Case reports, RCTs and reviews were excluded.

Studies investigating persistence were included if therapy survival probabilities, mean or median time to therapy discontinuation, or the proportion of patients discontinuing therapy within the study follow-up period were reported. Studies investigating effectiveness were included if they reported absolute change in PASI, the proportion of patients achieving PASI 50, PASI 75 or PASI 90 at ≥ 3 months (50%, 75% and 90% reductions in PASI, respectively), improvements in Physician's Global Assessment (PGA) at ≥ 3 months, or the proportion of patients discontinuing therapy due to ineffectiveness.

Study Selection

After the removal of duplicate reports, titles and abstracts were independently screened by two reviewers (S.W. and K.J.M.). The remaining articles were read in full, with data extracted by one reviewer (S.W.) and corroborated by the second (K.J.M.); any articles found to meet the exclusion criteria were removed. Reference lists of reviews were also hand searched to identify additional publications.

Data Extraction

The study characteristics extracted from each included article were author, study design and time period, therapies studied, number of patients per therapy, mean age, sex, mean disease duration, the proportion of patients with psoriatic arthritis, the mean baseline PASI and DLQI, and the proportion of patients using combination therapy. The outcomes of interest were extracted into a separate table along with the number of patients at each follow-up, where possible.

Quality Assessment

Two reviewers (S.W. and K.J.M.) determined the quality of the included observational studies using the Newcastle–Ottawa Quality Assessment Scale for Cohort Studies.[12] There are nine items included in the scale, with four items under 'selection' and four items under 'outcome' scored a maximum of one star each, with the final item 'comparability of cohorts' scored a maximum of two stars. Definitions and ratings of the biases are provided in Appendix S2 (see Supporting Information).

This review is reported according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and is registered with PROSPERO (CRD42018099771; date 19 June 2018).