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

Disclosures

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

In This Article

Results

The initial search produced 656 articles, with 411 remaining after deduplication (n = 245; Figure 1). After excluding 335 articles by title screening, 76 abstracts remained. Fifty-seven articles were excluded by abstract. Two additional articles were found through hand searching the reference lists of the included studies, with 21 articles read in full and assessed for eligibility. Of the 13 articles next excluded, three studies were removed by title or abstract due to having a cohort of < 100 patients (Appendix S3; see Supporting Information)[13–15] and 10 articles were excluded for ineligibility (Appendix S4; see Supporting Information).[16–25] No studies were excluded based on outcome definition alone. The remaining eight articles were included in the systematic review (Table 1).

Figure 1.

Flowchart of the article selection. Studies were identified by searching Embase, MEDLINE, PubMed and the Cochrane Library then filtered according to title, abstract and eligibility. Additional articles were identified by manually searching reference lists.

Study Characteristics

Acitretin, ciclosporin and methotrexate were included in one study,[26] FAE and methotrexate in one study,[27] methotrexate in two studies[28,29] and FAE in four[30–33] (Table 1). Four studies were retrospective and performed at a single centre,[27,28,30,31] while four were multicentre studies, three of which were prospective[26,29,33] and one retrospective.[32] All eight studies were European, with follow-up conducted from 2003 to 2014 and published in 2009–2017.

One study reported only the number of treatment cycles instead of the number of patients (158 cycles of FAE, 174 cycles of methotrexate)[27] and one study reported the baseline characteristics for the entire cohort instead of patients registering to each therapy.[29] Four studies reported the proportions of patients with no previous exposure to systemic psoriasis therapy (incident users).[26,28,31,32] Two of these four studies investigated FAE and reported 60%[31] and 81%[32] of the cohort as incident users, one study reported 67% of a methotrexate cohort as incident users[28] and one study reported the proportions of incident users of acitretin, ciclosporin and methotrexate as 54%, 46% and 51%, respectively.[26] One article reported the number of first-line treatment cycles for FAE (n = 116, 73%) and methotrexate (n = 70, 40%) as opposed to the number of systemic-naive patients.[27]

Seven of the eight articles examined therapy discontinuation time,[26–29,31–33] with six also reporting the proportion of patients discontinuing therapy (Table 2).[26–28,31–33] All eight studies reported effectiveness outcomes (Table 2 and Table S1; see Supporting Information), with six studies reporting the proportion of patients discontinuing therapy due to ineffectiveness[26–28,31–33] and the other two studies reporting the mean PASI, PASI 75 and PASI 90;[29] and PASI 50, PASI 75 and PASI 90 at 3-, 6- and 12-month time points.[30]

Persistence

Davila-Seijo et al. reported the probability of drug survival at 1 year as 42·3% for acitretin [95% confidence interval (CI) 36·9–47·6], 23·3% for ciclosporin (95% CI 19·0–27·8) and 50·3% for methotrexate (95% CI 46·3–54·2), with median discontinuation times of 0·72, 0·45 and 1·01 years, respectively (Table 2).[26] Over the 5-year study period 34%, 26% and 30% of patients discontinuing acitretin, ciclosporin and methotrexate, respectively, did so for ineffectiveness (Table S1), with 14%, 18% and 17% discontinuing for adverse events.[26]

One study reported mean treatment durations of 35·6 months (95% CI 27·8–43·5) and 22·3 months (95% CI 17·6–27·1) for FAE and methotrexate, respectively; the most common reasons for discontinuation during the 5-year study period were adverse events and ineffectiveness (42% and 21%, respectively, for FAE; 22% and 21% for methotrexate; Table S1).[27] Two studies reported the mean duration of FAE therapy as 28 months (range 1 week to 106 months)[31] and 50 months (no range),[32] with another two studies reporting mean durations of methotrexate therapy of 17·2 ± 13·6 months[28] and 7·7 months (range 0–36;[29]Table S1). The most common reasons for discontinuation among studies reporting the proportion of patients discontinuing FAE were adverse events (46% over 4 years;[31] 43% over 1 year)[33] and ineffectiveness (22% over 36 months),[32] and adverse events for methotrexate (22% over 48 weeks;[28] Table S1).

Effectiveness

Mean PASI values at baseline and 12 months were reported in two studies; Walker et al. reported mean PASI of 16·8 and 5·6, respectively, for patients receiving FAE,[33] while Maul et al. reported mean PASI of 11·4 and 2·2, respectively, for patients receiving methotrexate (Table 2).[29] Two studies reported that 76% of FAE patients on therapy at 1 year achieved PASI 75[30] and PGA of markedly improved or clear.[32] Two studies reported that 53%[28] and 59%[29] of patients on methotrexate remaining on therapy at 1 year achieved PASI 75 (Table 2). Two studies also reported discontinuations due to ineffectiveness for FAE (40% over 4 years;[31] 11% over 1 year)[33] and one for methotrexate (21% over 48 weeks;[28] Table S1). Effectiveness outcomes with PASI or PGA were not reported for ciclosporin or acitretin.

Quality Assessment

Two studies were rated as 'high quality'[26,27] (scored > 7), with the remaining six studies rated 'medium quality'[28–33] (scored 4–6). None of the six studies rated as 'medium quality' adjusted for age, sex or any other confounding factors in their persistence or effectiveness analyses.[28–33] A meta-analysis was not conducted due to the diverse study designs, outcome definitions and analytical approaches used (Table 3).

Comments

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