Abstract
Introduction
Scalp psoriasis affects up to 80% of patients with plaque-type psoriasis and is often resistant to topical and conventional systemic agents. There is a lack of consensus on a “gold standard” treatment.
Objective
This comprehensive review and network meta-analysis aimed to compare the efficacy and safety of studied interventions.
Methods
The Ovid MEDLINE(R), Embase, and Cochrane databases were searched from 01 January 2000 to 05 October 2022. All English-language randomized controlled trials evaluating an intervention for scalp psoriasis were included if they reported one of the following clinical outcomes: Psoriasis Scalp Severity Index (PSSI), scalp Physician Global Assessment (ScPGA), scalp-specific Investigator or Physician Global Assessment (IGA/PGA), and Total Sign Score (TSS), and adverse events. A random effects network meta-analysis was performed where possible, and network plots were generated.
Results
Of 1,046 studies identified, 35 met the inclusion criteria, with seven in the PSSI analysis and 16 in the IGA analysis. All interventions led to an improvement in all outcomes when compared to placebo in the PSSI and PGA/IGA. For the PSSI response, secukinumab 300 mg every four weeks (Q4W) was the most effective (SUCRA 0.991). For the PGA/IGA response, bimekizumab 320 mg Q4W was the most effective (SUCRA 0.975).
Conclusions
Several systemic therapies are superior to placebo in improving clinical outcomes, with secukinumab 300 mg Q4W and bimekizumab 320 mg Q4W deemed the most effective among biologic agents analyzed. Efforts to enhance research standardization, including head-to-head trials with standardized outcome measures, diverse patient recruitment, and long-term follow-up, are crucial next steps in assessing treatment efficacy and adverse events.
Keywords: scalp psoriasis, treatment outcome, biologic agents, antipsoriatic agents, network meta-analysis, randomized controlled trials, comparative efficacy, systematic review
Introduction
Up to 80% of patients with plaque-type psoriasis have scalp involvement [1]. Scalp psoriasis can cause significant physical and social distress, with up to 97% reporting that the condition interferes in their daily life [2]. Many individuals experience intense pruritus and pain associated with their disease, and the shedding of scale as dandruff can cause significant social embarrassment for affected individuals [3]. Notably, patients have reported significant psychosocial distress and withdrawal from social activities as a result of embarrassment from not being able to hide their lesions [1, 4–6]. Scalp psoriasis is also often refractory to topical agents [1, 7, 8]. Overall, scalp psoriasis continues to pose a significant challenge for dermatologists due to the lack of effective therapies and the severe physical and psychosocial impact on affected patients.
Additionally, outcome measures to quantify the severity of scalp psoriasis are heterogeneous and have varied across various clinical studies. Commonly-used scalp psoriasis tools include the Psoriasis Scalp Severity Index (PSSI), scalp Physician Global Assessment (ScPGA), scalp-specific Investigator or Physician Global Assessment (IGA/PGA), and Total Sign Score (TSS). The PSSI score is calculated by assessing erythema, scaliness, induration, and extent of scalp psoriasis involvement [5]. ScPGA is a seven-point scale assessing plaque elevation, scaling, and erythema [9]. The TSS has been used differently in the studies, with some including only erythema, scaling, and thickness, and others also including pruritus [8]. Instruments that measure patient-reported outcomes such as quality of life and symptom burden also exist but are less often used. These include the Dermatology Life Quality Index (DLQI) and Scalpdex [5].
Previous reviews and meta-analyses on scalp psoriasis found a therapeutic benefit among biologics and small molecule agent (SMAs) treatments compared to placebo [4, 7]. There is a lack of consensus on the optimal or most effective treatment for scalp psoriasis mostly due to the limited number of head-to-head trials comparing biologics and SMAs. We conducted a systematic review and network meta-analysis on systemic therapies for scalp psoriasis.
Objectives
The objective of this study was to compare the efficacy of various therapies for the treatment of scalp psoriasis.
Methods
Search Strategy and Selection Criteria
A systematic review of the literature was conducted of the Ovid MEDLINE(R), Embase, and Cochrane Central Register of Controlled Trials databases from 01 January 2000 to 05 October 2022. All full-text works published in English were included in the analysis if they answered the research question outlined using the Population, Intervention, Comparison, and Outcome (PICO) method: P) patients with any severity of scalp psoriasis; I and C) any therapy type (topical agents, SMAs, biologics, phototherapy, and other); and O) change in scalp psoriasis as determined by improvement and changes in PSSI score, IGA score, ScPGA, modified Psoriasis Area and Severity Index (mPASI) score, or TSS [10]. Works were excluded for the following reasons: only reporting outcomes beyond 24 weeks from baseline (denoted as “remission therapy”), non-randomized studies, abstract-only studies, non-English language, pediatric populations, or non-human models. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, two authors (TB and RPL) screened all titles and abstracts independently for eligibility and discussed any discrepancies [11]. All full texts of studies were then for eligibility, and all extracted data were cross-referenced by two reviewers (TB and RPL) to ensure accuracy. For each outcome, data were only extracted between baseline and the 24-week time point, which was denoted as “induction therapy.”
Data Collection
Across studies included, data were extracted on demographics, sample size, publication year, treatment characteristics (dosing, frequency), comparison group, timing of outcome assessment, key findings, and others. PSSI, IGA/PGA, ScPGA, mPASI, TSS, and adverse event outcome data were also extracted. Outcomes assessed at 12 weeks were included in the analysis. For studies that did not report 12-week data, the time point closest to 12 weeks was included for analysis purposes (ranging from four to sixteen weeks). The risk of bias of each trial was also assessed in accordance with the Cochrane Risk of Bias Tool for Randomized Controlled Trials (RoB 2) [12].
Statistical Analysis
A random-effects network meta-analysis was performed using R statistical software (Netmeta package). Within the outcome domain, standardized mean differences (SMD) were employed to combine different scales to allow for the consideration of all the studies reporting a given outcome. Studies of four to sixteen weeks of treatment were pooled, and the analysis was conducted using intention-to-treat (ITT) data. In these analyses, dosing schedules were treated as their own network nodes (i.e., results of different administration schedules of medications were not pooled). Network plots were generated for the analysis. Summary results are presented as SMDs with a 95% confidence interval (CI). Effect estimates for all pairwise comparisons in the network were also calculated.
Results
Characteristics of Included Studies
Through an initial search of the databases, 1,046 studies were identified, of which 702 remained after duplicates were removed (Figure 1); 184 studies were assessed for eligibility, and a total of 35 RCTs were selected for inclusion in the systematic review, of which 19 were included in the network meta-analysis [9, 13–46]. The study characteristics for all included RCTs are summarized in Table S1. Across included studies, there was only sufficient evidence available on systemic agents to include PSSI and scalp or scalp-specific IGA outcomes in a network meta-analysis. Twenty-two studies included a biologic as part of the treatment arm (62.3%), with guselkumab being the most commonly used (N=4, 11.4%). A similar number of studies had nonsteroidal topical therapy as part of at least one treatment arm (N=25, 71.4%). Fifteen studies included a topical corticosteroid as part of the treatment arms (42.9%), with betamethasone dipropionate used in almost half of these trials (N=7, 20%). Placebo was used as the control arm in the majority of the studies (N=23, 65.7%). Of the studies for which the blinding status was known, the majority of the studies were double-blinded (N=23, 65.7%). Detailed baseline demographic characteristics for each included study are included in Table 1. Of note, studies that reported on topical therapies only were not included in the network meta-analysis. In total, 11 studies examined only these agents, which included betamethasone valerate, betamethasone dipropionate, calcipotriol, calcipotriene, and combinations of these therapies [9, 23–25, 27–32, 40].
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.
Table 1.
Baseline Characteristics of Included Studies.
| Author | Arms | Caucasian (%) | Male (%) | Age [min-max] (years) | Mean BMI | Psoriasis Duration (Years) | Scalp involvement (%) | PSSI | TSS | IGA/PGA score of 3–5 (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| Bagel J [13] | Secukinumab 300 mg | 86.3 | 52.9 | 42.7* | 31.2* | 14.4* | 61.6* | 33.4* | NR | 84.3, 70.6, NR |
| Placebo | 74.5 | 41.2 | 41.1* | 31.9* | 15.4* | 59.3* | 33* | NR | 15.7, 29.4, NR | |
| Buckley C [23] | Calcipotriol/ene+ Betamethasone Dipropionate | 97.2 | 43.5 | 48.4* | NR | 16* | NR | NR | 6.79* | NR |
| Betamethasone Dipropionate | 98.2 | 46.4 | 48.4* | NR | 13.2* | NR | NR | 6.81* | NR | |
| Elewski B [14] | Brodalumab 210 mg | NR | NR | NR | NR | 20.4* | NR | 16.7- | NR | NR |
| Placebo | NR | NR | NR | NR | 20.7* | NR | 20* | NR | NR | |
| Bagel J [15] | Etanercept 50 mg | 69.5 | 53.2 | 39- [18–71] | 30.2- | 17.5- | 72.5- | 35- | NR | NR |
| Placebo | 75.8 | 58.1 | 42- [18–70] | 30.1- | 11.9- | 60- | 30- | NR | NR | |
| Bahraini P [41] | Turmeric tonic | NR | 40 | 29- [27–35] | NR | NR | NR | NR | NR | NR |
| Placebo | NR | 20 | 44- [29–50] | NR | NR | NR | NR | NR | NR | |
| Feldman SR [9] | Betamethasone valerate BID | NR | 45.57 | 50* [17–90] | NR | NR | NR | NR | 7.7* | NR |
| Betamethasone valerate QD | NR | 45.57 | 50* [17–90] | NR | NR | NR | NR | 8.1* | NR | |
| Jemec GBE [24] | Calcipotriol/ene+ Betamethasone Dipropionate | 95.7 | 47.9 | 47.9* [18–83] | NR | 15.4* | NR | NR | 6.7* | 56.2, 28.2, 6.3 |
| Calcipotriene/ol | 97.4 | 44.5 | 50.1* [17–91] | NR | 16.7* | NR | NR | 6.8* | 57.4, 32, 4.8 | |
| Betamethasone Dipropionate QD | 96.8 | 41.9 | 49.5*[18–91] | NR | 17.4* | NR | NR | 6.9* | 57, 32.9, 5.6 | |
| Placebo | 94.9 | 44.9 | 49.6* [18–97] | NR | 16.3* | NR | NR | 7* | 50.7, 36, 5.9 | |
| Jury CS [42] | Itraconazole | NR | 42.85 | 47- | NR | NR | NR | NR | NR | NR |
| Placebo | NR | 42.85 | 47- | NR | NR | NR | NR | NR | NR | |
| Kragballe K [25] | Calcipotriol/ene+ Betamethasone Dipropionate | 99 | 43.5 | 50.8* [18–91] | NR | 18.4* | NR | NR | 7.4* | 54.6, 37.7, 7.7 |
| Calcipotriene/ol | 99 | 41.9 | 51.4* [24–85] | NR | 19.3* | NR | NR | 7.1* | 61, 32.4, 6.7 | |
| Liu L [26] | Calcipotriol/ene+ Betamethasone Dipropionate | 0 | 67.6 | 40.9* [18–81] | 24.05* | 8.278* | NR | NR | NR | 56.7, 27.1, 1.8 |
| Calcipotriene/ol | 0 | 66.1 | 39.9* [18–76] | 24.05* | 7.517* | NR | NR | NR | 56, 23.6, 1 | |
| Ma L [27] | Calcipotriol/ene+ Betamethasone Dipropionate | NR | 60.8 | 39.9* | NR | 7.4* | 54.1* | NR | 6.8* | 69.2, 24.4, 6.7 |
| Calcipotriene/ol | NR | 55.6 | 38.7* | NR | 7.5* | 48.6* | NR | 6.9* | 70.2, 25.8, 4 | |
| Okubo Y [40] | Betamethasone butyrate propionate + maxacalcitol (8 weeks) | NR | 87.5 | 49.6* [24–78] | NR | 14.1* | NR | NR | 5.6* | NR |
| Betamethasone butyrate propionate + maxacalcitol (4 weeks) | NR | 80 | 46.1* [26–76] | NR | 7.3* | NR | NR | 5.4* | NR | |
| van de Kerkhof PC [28] | Calcipotriol/ene+ Betamethasone Dipropionate | 98.4 | 41.9 | 48.5* [18–92] | NR | 15.7* | NR | NR | 6.8* | 54.8, 29.9, 5.5 |
| Betamethasone Dipropionate QD | 96.8 | 46.2 | 47.9* [18–85] | NR | 16.1* | NR | NR | 6.9* | 53.6, 33.6, 4.8 | |
| Calcipotriene/ol | 95.8 | 47.9 | 48.7* [18–88] | NR | 15.8* | NR | NR | 6.8* | 51.4, 32.9, 3.5 | |
| Patel DS [29] | Calcipotriol/ene+ Betamethasone Dipropionate | 93 | 53 | 47.4* [20–81] | NR | 14.6* | NR | NR | NR | 65, 17, NR |
| Calcipotriene/ol | 91.1 | 60.4 | 50.7* [21–85] | NR | 18.4* | NR | NR | NR | 62.4, 14.9, NR | |
| Betamethasone Dipropionate QD | 82.2 | 55.4 | 49* [20–85] | NR | 16.2* | NR | NR | NR | 71.3, 9.9, NR | |
| Rattanakaemakorn P [21] | Excimer lamp + 10% LCD cream | NR | 46.7 | 35.53* | 27.15* | NR | NR | 12- | NR | NR |
| Excimer lamp | NR | 40 | 47* | 29.1* | NR | NR | 18- | NR | NR | |
| Reich K [16] | Etanercept 50 mg | 92.4 | 68.7 | 45.4* | NR | 18.6* | NR | 19.9* | NR | NR |
| Ixekizumab Q2W | 93.2 | 65.3 | 44.8* | NR | 18.7* | NR | 20.3* | NR | NR | |
| Ixekizumab Q4W | 92.2 | 67.9 | 45.2* | NR | 18.7* | NR | 20.1* | NR | NR | |
| Placebo | 91.4 | 71.2 | 46* | NR | 18.8* | NR | 20.8* | NR | NR | |
| Reygagne P [30] | Clobetasol propionate shampoo | NR | 49 | 44.9* | NR | NR | 46* | NR | 4.86* | NR |
| Calcipotriene/ol | NR | 45 | 45.7* | NR | NR | 44* | NR | 4.95* | NR | |
| Rich P [43] | Apremilast 30 mg | NR | 65.2 | 44.9* | NR | 19.14* | NR | NR | NR | 64.7, 35.3, NR |
| Placebo | NR | 65.1 | 45.1* | NR | 17.41* | NR | NR | NR | 62.4, 37.6, NR | |
| Apremilast 30 mg | NR | 58.5 | 44.7* | NR | 17.78* | NR | NR | NR | 68.8, 31.3, NR | |
| Placebo | NR | 75.3 | 44.1* | NR | 17.52* | NR | NR | NR | 58.1, 41.9, NR | |
| Saraceno R [31] | Calcipotriol/ene+ Betamethasone Dipropionate | NR | 51 | 44.1* [18–85] | NR | NR | 37.3* | NR | 6.9* | NR |
| Calcipotriol/ene+ Betamethasone Dipropionate | NR | 59.2 | 45.7* [18–84] | NR | NR | 36.8* | NR | 6.8* | NR | |
| Tyring S [32] | Calcipotriol/ene+ Betamethasone Dipropionate | 0 | 62.2 | 44.4* [18–75] | NR | 10.5* | NR | NR | 6.3* | 81.5, NR, NR |
| Placebo | 0 | 66.7 | 45.8* [22–76] | NR | 11.8* | NR | NR | 6.2* | 76.2, NR, NR | |
| Van Voorhees S [33] | Apremilast 30 mg | 76.6 | 62.2 | 47* | 30.7* | 15.7* | 61.9* | NR | NR | 76.1, 23.9, NR |
| Placebo | 73.5 | 60.8 | 46.7* | 31.7* | 14.8* | 58.2* | NR | NR | 74.5, 25.5, NR | |
| Zhou J [22] | UVA1 phototherapy | NR | 61.76 | 32.7* [21–53] | NR | 3.02* | NR | 15.28* | NR | NR |
| Narrow band UVB phototherapy | NR | 61.76 | 32.7* [21–53] | NR | 3.02* | NR | 15.5* | NR | NR | |
| Thaçi D [20] | Risankizumab 150 mg | NR | NR | 42* [18–73] | NR | NR | NR | 23.1* | NR | NR |
| Fumaric acid esters | NR | NR | 42.5* [19–69] | NR | NR | NR | 20.2* | NR | NR | |
| Blauvelt A [44] | Placebo | NR | NR | NR | NR | NR | NR | NR | NR | 59.3, 16.7, NR |
| Guselkumab 100 mg | NR | NR | NR | NR | NR | NR | NR | NR | 58.8, 19.6, NR | |
| Adalimumab 80 mg | NR | NR | NR | NR | NR | NR | NR | NR | 59.3, 19.3, NR | |
| Reich K [34] | Placebo | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Guselkumab 100 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Adalimumab 80 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Ohtsuki M [35] | Placebo | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Guselkumab 50 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Guselkumab 100 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Thaçi D [36] | Guselkumab 100 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Fumaric acid esters | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Seo SJ [17] | Placebo | NR | NR | NR | NR | NR | NR | 28* | NR | NR |
| Brodalumab 210 mg | NR | NR | NR | NR | NR | NR | 24.6* | NR | NR | |
| Nakagawa H [18] | Placebo | NR | NR | NR | NR | NR | NR | 26.2* | NR | NR |
| Brodalumab 70 mg | NR | NR | NR | NR | NR | NR | 25.8* | NR | NR | |
| Brodalumab 140 mg | NR | NR | NR | NR | NR | NR | 26.5* | NR | NR | |
| Brodalumab 210 mg | NR | NR | NR | NR | NR | NR | 24.3* | NR | NR | |
| Reich K [37] | Bimekizumab | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Ustekinumab 45 or 90 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Placebo | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Gordon KB [38] | Bimekizumab 320 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Placebo | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Langley RG [19] | Ixekizumab 10 mg | NR | NR | NR | NR | NR | NR | 19.5* | NR | NR |
| Ixekizumab 25 mg | NR | NR | NR | NR | NR | NR | 20.5* | NR | NR | |
| Ixekizumab 75 mg | NR | NR | NR | NR | NR | NR | 13.8* | NR | NR | |
| Ixekizumab 150 mg | NR | NR | NR | NR | NR | NR | 20.1* | NR | NR | |
| Placebo | NR | NR | NR | NR | NR | NR | 18.8* | NR | NR | |
| Lebwohl MG [39] | Calcipotriol/ene+ Betamethasone Dipropionate | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Calcipotriene/ol | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Betamethasone Dipropionate QD | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Bergstrom KB [45] | Clobetasol propionate foam | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Clobetasol propionate solution | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Stein Gold L [46] | Apremilast 30 mg | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Placebo | NR | NR | NR | NR | NR | NR | NR | NR | NR |
Abbreviations: BID: twice a day; Calcipotriol/ene: combination therapy of calcipotriol and calcipotriene; Calcipotriene/ol: combination therapy of calcipotriene and calcipotriol; QD; once daily,
indicates this value is a mean,
indicates this value is a median
Network Meta-Analysis Results
PSSI Response
From all studies measuring PSSI response as an outcome, seven studies were included in the analysis [13–19]. One study was excluded due to a lack of information on the standard deviation of the mean PSSI [20], and two additional studies were excluded for including three treatments that formed a separate subnetwork which was not connected to the other treatments in the network [21, 22]. The treatments included in the analysis were: etanercept 50 mg twice weekly, secukinumab 300 mg every four weeks (Q4W), brodalumab 210 mg every two weeks (Q2W), ixekizumab 150 mg Q2W, ixekizumab 160 mg followed by 80 mg Q2W, and ixekizumab 160 mg followed by 80 mg Q4W. The treatment network formed by the included studies is depicted in Figure 2A. All interventions led to a statistically significant improvement in PSSI response compared to placebo, indicating a potentially beneficial effect in reducing the extent and severity of psoriasis involvement (Figure 2B and Table S1). When compared to each other, secukinumab 300 mg Q4W was found to be the safest and most effective (SUCRA 0.991) followed by ixekizumab 160 mg Q2W, (SUCRA 0.701), ixekizumab 150 mg Q2W, (SUCRA 0.671), ixekizumab 160 mg Q4W (SUCRA 0.605), brodalumab 210 mg Q2W, (SUCRA 0.302), and etanercept 50 mg twice weekly (SUCRA 0.230).
Figure 2.
(A) Network plot of studies reporting the PSSI response. (B) Forest plot of network meta-analysis results for studies reporting the PSSI response. (PSSI = Psoriasis Scalp Severity Index.)
Scalp or Scalp-Specific PGA/IGA Response
Seven studies were included in the analysis for the outcome of the IGA response [9, 13, 16 23–39]. Guselkumab 50 mg every eight weeks (Q8W), guselkumab 100 mg Q8W, adalimumab 80 mg Q2W, apremilast 30 mg twice daily, secukinumab 300 mg Q4W, bimekizumab 320 mg Q4W, and ustekinumab 90 mg Q12W were the treatments included in the analysis (Figure 3A).
Figure 3.
(A) Network plot of studies reporting the IGA response. (B) Forest plot of network meta-analysis results for studies reporting the IGA response. (IGA = scalp-specific Investigator Global Assessment).
In comparison to the placebo, all interventions led to a reduction in IGA, indicating a potentially beneficial effect in improving symptoms (Figure 3B and Table S1). Aside from guselkumab 50 mg Q8W, all interventions had a statistically significant benefit when compared to placebo. According to the SUCRA analysis, bimekizumab 320 mg Q4W had the highest likelihood of improving IGA scores (SUCRA 0.975), followed by ustekinumab 90 mg Q12W (SUCRA 0.7050), secukinumab 300 mg Q4W (SUCRA 0.6374), guselkumab 100 mg Q8W (SUCRA 0.5194), apremilast 30 mg twice daily (SUCRA 0.5071), adalimumab 80 mg Q2W, (SUCRA 0.4384), and guselkumab 50 mg Q8W (SUCRA 0.2023).
Risk of Bias Assessment
The risk of bias assessment for the included studies in the network meta-analysis revealed varying degrees of methodological quality across different trials. Overall, most studies exhibited a low risk of bias in random sequence generation, blinding of participants and personnel, blinding of outcome assessment, and incomplete outcome data. However, there were instances of unclear or high risk of bias in certain domains, particularly in the allocation concealment, selective reporting, and other biases domains. In total, six out of 24 studies had a high risk of bias in at least one domain, while 20 studies had an unclear risk of bias in at least one domain.
Conclusions
Though corticosteroids are commonly used in the treatment of scalp psoriasis, they are suboptimal in severe or resistant cases, and long-term use is associated with adverse side effects, including skin lesions and atrophy, highlighting a need for newer, systemic therapeutic modalities [6, 47, 48]. In this analysis, all included therapies showed significant efficacy when compared to placebo through various measures, including PSSI response and IGA response. When all interventions were compared against each other, secukinumab 300 mg and bimekizumab 320 mg were found to be the most effective in improving the PSSI and PGA/IGA scores, respectively.
Among biologics compared in the PSSI and IGA response analyses, biologic agents outperformed other small molecules, aside from a 50-mg dosing of guselkumab, which is not used in real life. In the PSSI analysis, the biologic agents (secukinumab 300 mg Q4W, brodalumab 210 mg Q2W, and ixekizumab 150/160 mg Q2–4W) had a higher likelihood of being more effective than etanercept 50 twice weekly, which is consistent with previous studies [7, 16]. In the IGA response analysis, bimekizumab 320 mg Q4W, ustekinumab, secukinumab 300 mg Q4W, and the 100 mg dosing of guselkumab Q8W were deemed to be more effective than other biologic and small molecule therapies, including apremilast 30 mg twice daily and adalimumab 80 mg Q2W. This is consistent with previous head-to-head comparative studies [49]. These results, consistent with previous research, indicate that the use of newer biologics may be linked to better clinical performance and control of scalp psoriasis symptoms, thus improving quality of life [47].
Scalp psoriasis treatment is greatly expanding, including over 10 different biologic drugs and one small molecule. Scalp psoriatic plaques are particularly refractory to topical and phototherapeutic treatments due to the presence of hair, and patients often struggle with adherence due to poor cosmetic results [1, 7, 8]. However, current clinical decisionmaking tools still endorse topical corticosteroids as the first-line treatment for patients, and agents such as ciclosporin, methotrexate, fumaric esters, and acitretin as second-line agents for moderate-severe or treatment-resistant psoriasis [50]. Despite their clear advantages, the widespread adoption of biologics in psoriasis treatment is constrained by cost, administration challenges, and uncertainties surrounding long-term efficacy and safety. Foremost among these is the substantial cost associated with biologics, far exceeding that of traditional medications. Despite efforts such as patient assistance programs and savings coupons, cost-related barriers persist, leading to discontinuation of treatment and hindering cost-effective care. Moreover, the need for injections or infusions adds another layer of inconvenience, impacting adherence and posing logistical challenges particularly for travelers who must navigate storage and transportation requirements. Additionally, while biologics offer promise for long-term maintenance due to their lower toxicity compared to alternatives, uncertainties remain regarding their efficacy and safety over extended periods. Limited long-term clinical data and the potential for patients to develop anti-drug antibodies raise concerns about treatment durability and effectiveness [51].
Limitations
The strengths of this review include its comprehensive nature, encompassing a wide range of treatments and outcome measures for scalp psoriasis, the use of a network meta-analysis methodology to compare these simultaneously, and a systematic approach enhancing the reliability and validity of the findings. However, this study was not without limitations. Due to the heterogeneity in the timing of outcome reporting, trials with durations between 8 and 12 weeks were pooled, and trials beyond 12 weeks were included, which may have favored treatments with longer trial durations and thus increased time to improve psoriasis. Combining different dosing regimens of treatments to incorporate more information may also have introduced limitations due to heterogeneity and comparability issues across the different treatment groups. This analysis was further limited by differences in trial design and heterogeneity in the populations involved. For example, though most studies that reported race-/ethnicity-based data had a majority of Caucasian populations, there were some studies with only racial minorities and significant heterogeneity in the country of study completion. The generalizability of these results is also limited in populations underrepresented in the included clinical trials, such as racial minorities and older patients.
In summary, this systematic review and network meta-analysis offer new insights into the range of treatments for scalp psoriasis. There is a critical need for effective therapies for scalp psoriasis given its significant impact on patients’ quality of life. The findings of this study highlight the efficacy of various treatments in improving symptoms, with secukinumab 300 mg Q4W and bimekizumab 320 mg Q4W deemed most effective in improving PSSI and IGA, respectively. These interventions were deemed most effective among biologic agents analyzed, indicating that they may be helpful among patients with moderate-to-severe scalp psoriasis that is refractory to traditional first-line treatments. To address these limitations, future studies should conduct head-to-head trials comparing various treatments directly, using standardized outcome measures and consistent timing of assessments. In this study, certain studies found in the systematic review could not be included as they did not use an outcome that was being assessed for the network meta-analysis. Thus, standardization is not only crucial for the generalizability of the results but also to facilitate evidence synthesis. Furthermore, there should be efforts to recruit a more diverse patient population for clinical trials to increase the generalizability of findings to underrepresented groups. Lastly, studies with long-term follow-up are needed to assess adverse events associated with prolonged therapy and the durability of treatment responses over time.
Supplementary Information
Acknowledgements
Ms. Behroozian received funding support for this project as a recipient of the McMaster Medical Student Research Excellence Scholarships.
Footnotes
Competing Interests: TB, HK PL, SC, and DC declare no conflict of interest. MAH has been speaker, advisor, and/or received honoraria from: AbbVie, Biojamp, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Hikma Pharmaceuticals, Incyte, Janssen, Leo, L’Oreal, La Roche Posay, Medexus, Novartis, Pfizer, Recordati, Sanofi Regeneron, Sun Pharma.
Authorship: All authors have contributed significantly to this publication.
Funding: None.
References
- 1.van de Kerkhof PC, de Hoop D, de Korte J, Kuipers MV. Scalp psoriasis, clinical presentations and therapeutic management. Dermatology. 1998;197(4):326–34. doi: 10.1159/000018026. [DOI] [PubMed] [Google Scholar]
- 2.Crowley J. Scalp psoriasis: an overview of the disease and available therapies. J Drugs Dermatol. 2010;9(8):912–8. [PubMed] [Google Scholar]
- 3.Mrowietz U, Macheleidt O, Eicke C. Effective treatment and improvement of quality of life in patients with scalp psoriasis by topical use of calcipotriol/betamethasone (Xamiol®-gel): results. J Dtsch Dermatol Ges. 2011;9(10):825–31. doi: 10.1111/j.1610-0387.2011.07695.x. [published Online First: 20110512] [DOI] [PubMed] [Google Scholar]
- 4.Wang TS, Tsai TF. Managing Scalp Psoriasis: An Evidence-Based Review. Am J Clin Dermatol. 2017;18(1):17–43. doi: 10.1007/s40257-016-0222-4. [DOI] [PubMed] [Google Scholar]
- 5.Blakely K, Gooderham M. Management of scalp psoriasis: current perspectives. Psoriasis (Auckl) 2016;6:33–40. doi: 10.2147/ptt.S85330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Chan CS, Van Voorhees AS, Lebwohl MG, et al. Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2009;60(6):962–71. doi: 10.1016/j.jaad.2008.11.890. [DOI] [PubMed] [Google Scholar]
- 7.Alsenaid A, Ezmerli M, Srour J, Heppt M, Illigens BM, Prinz JC. Biologics and small molecules in patients with scalp psoriasis: a systematic review. J Dermatolog Treat. 2022;33(1):473–82. doi: 10.1080/09546634.2020.1770167. [published Online First: 20200619] [DOI] [PubMed] [Google Scholar]
- 8.Schlager JG, Rosumeck S, Werner RN, et al. Topical treatments for scalp psoriasis. Cochrane Database Syst Rev. 2016;2(2):Cd009687. doi: 10.1002/14651858.CD009687.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Feldman SR, Ravis SM, Fleischer AB, Jr, et al. Betamethasone valerate in foam vehicle is effective with both daily and twice a day dosing: a single-blind, open-label study in the treatment of scalp psoriasis. J Cutan Med Surg. 2001;5(5):386–9. doi: 10.1007/s10227-001-0005-1. [DOI] [PubMed] [Google Scholar]
- 10.Aslam S, Emmanuel P. Formulating a researchable question: A critical step for facilitating good clinical research. Indian J Sex Transm Dis AIDS. 2010;31(1):47–50. doi: 10.4103/0253-7184.69003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898. [DOI] [PubMed] [Google Scholar]
- 13.Bagel J, Duffin KC, Moore A, et al. The effect of secukinumab on moderate-to-severe scalp psoriasis: Results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study. J Am Acad Dermatol. 2017;77(4):667–74. doi: 10.1016/j.jaad.2017.05.033. [published Online First: 20170802] [DOI] [PubMed] [Google Scholar]
- 14.Elewski B, Rich P, Lain E, Soung J, Lewitt GM, Jacobson A. Efficacy of brodalumab in the treatment of scalp and nail psoriasis: results from three phase 3 trials. J Dermatolog Treat. 2022;33(1):261–65. doi: 10.1080/09546634.2020.1749546. [DOI] [PubMed] [Google Scholar]
- 15.Bagel J, Lynde C, Tyring S, Kricorian G, Shi Y, Klekotka P. Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept. J Am Acad Dermatol. 2012;67(1):86–92. doi: 10.1016/j.jaad.2011.07.034. [published Online First: 20111020] [DOI] [PubMed] [Google Scholar]
- 16.Reich K, Leonardi C, Lebwohl M, et al. Sustained response with ixekizumab treatment of moderate-to-severe psoriasis with scalp involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2, UNCOVER-3) J Dermatolog Treat. 2017;28(4):282–87. doi: 10.1080/09546634.2016.1249820. [DOI] [PubMed] [Google Scholar]
- 17.Seo SJ, Shin BS, Lee JH, Jeong H. Efficacy and safety of brodalumab in the Korean population for the treatment of moderate to severe plaque psoriasis: A randomized, phase III, double-blind, placebo-controlled study. J Dermatol. 2021;48(6):807–17. doi: 10.1111/1346-8138.15733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Nakagawa H, Niiro H, Ootaki K. Brodalumab, a human anti-interleukin-17-receptor antibody in the treatment of Japanese patients with moderate-to-severe plaque psoriasis: Efficacy and safety results from a phase II randomized controlled study. J Dermatol Sci. 2016;81(1):44–52. doi: 10.1016/j.jdermsci.2015.10.009. [DOI] [PubMed] [Google Scholar]
- 19.Langley RG, Rich P, Menter A, et al. Improvement of scalp and nail lesions with ixekizumab in a phase 2 trial in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol. 2015;29(9):1763–70. doi: 10.1111/jdv.12996. [DOI] [PubMed] [Google Scholar]
- 20.Thaçi D, Eyerich K, Pinter A, et al. Direct comparison of risankizumab and fumaric acid esters in systemic therapy-naïve patients with moderate-to-severe plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2022;186(1):30–39. doi: 10.1111/bjd.20481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Rattanakaemakorn P, Triyangkulsri K, Iamsumang W. Suchonwanit P308-nm Excimer Lamp vs. Combination of 308-nm Excimer Lamp and 10% Liquor Carbonis Detergens in Patients With Scalp Psoriasis: A Randomized, Single-Blinded, Controlled Trial. Front Med (Lausanne) 2021;8:677948. doi: 10.3389/fmed.2021.677948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Zhou J, Yi X, Li Y, Ding Y. Efficacy assessment of UVA1 and narrowband UVB for treatment of scalp psoriasis. Lasers Med Sci. 2018;33(9):1979–82. doi: 10.1007/s10103-018-2564-z. [DOI] [PubMed] [Google Scholar]
- 23.Buckley C, Hoffmann V, Shapiro J, Saari S, Cambazard F, Milsgaard M. Calcipotriol plus betamethasone dipropionate scalp formulation is effective and well tolerated in the treatment of scalp psoriasis: a phase II study. Dermatology. 2008;217(2):107–13. doi: 10.1159/000130425. [DOI] [PubMed] [Google Scholar]
- 24.Jemec GBE, Ganslandt C, Ortonne J-P, et al. A new scalp formulation of calcipotriene plus betamethasone compared with its active ingredients and the vehicle in the treatment of scalp psoriasis: A randomized, double-blind, controlled trial. J Am Acad Dermatol. 2008;59(3):455–63. doi: 10.1016/j.jaad.2008.04.027. [DOI] [PubMed] [Google Scholar]
- 25.Kragballe K, Hoffmann V, Ortonne JP, Tan J, Nordin P, Segaert S. Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulation compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized controlled trial. Br J Dermatol. 2009;161(1):159–66. doi: 10.1111/j.1365-2133.2009.09116.x. [DOI] [PubMed] [Google Scholar]
- 26.Liu L, Zhang C, Wang J, et al. Comparison of safety and efficacy between calcipotriol plus betamethasone dipropionate gel and calcipotriol scalp solution as long-term treatment for scalp psoriasis in Chinese patients: a national, multicentre, prospective, randomized, active-controlled phase 4 trial. Eur J Dermatol. 2020;30(5):580–90. doi: 10.1684/ejd.2020.3876. [DOI] [PubMed] [Google Scholar]
- 27.Ma L, Yang Q, Yang H, et al. Calcipotriol plus betamethasone dipropionate gel compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized, controlled trial investigating efficacy and safety in a Chinese population. Int J Dermatol. 2016;55(1):106–13. doi: 10.1111/ijd.12788. [DOI] [PubMed] [Google Scholar]
- 28.van de Kerkhof PC, Hoffmann V, Anstey A, et al. A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. Br J Dermatol. 2009;160(1):170–6. doi: 10.1111/j.1365-2133.2008.08927.x. [DOI] [PubMed] [Google Scholar]
- 29.Patel DS, Veverka KA, Hansen JB, Yamauchi PS, Alonso-Llamazares J, Lebwohl M. Efficacy of Fixed-combination Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Foam for Scalp Plaque Psoriasis: Additional Analysis of a Phase II, Randomized Clinical Study. J Clin Aesthet Dermatol. 2020;13(5):12–18. [PMC free article] [PubMed] [Google Scholar]
- 30.Reygagne P, Mrowietz U, Decroix J, et al. Clobetasol propionate shampoo 0.05% and calcipotriol solution 0.005%: a randomized comparison of efficacy and safety in subjects with scalp psoriasis. J Dermatolog Treat. 2005;16(1):31–6. doi: 10.1080/09546630410024853. [DOI] [PubMed] [Google Scholar]
- 31.Saraceno R, Camplone G, D’Agostino M, et al. Efficacy and maintenance strategies of two-compound formulation calcipotriol and betamethasone dipropionate gel (Xamiol® gel) in the treatment of scalp psoriasis: results from a study in 885 patients. J Dermatolog Treat. 2014;25(1):30–3. doi: 10.3109/09546634.2013.800182. [DOI] [PubMed] [Google Scholar]
- 32.Tyring S, Mendoza N, Appell M, et al. A calcipotriene/betamethasone dipropionate two-compound scalp formulation in the treatment of scalp psoriasis in Hispanic/Latino and Black/African American patients: results of the randomized, 8-week, double-blind phase of a clinical trial. Int J Dermatol. 2010;49(11):1328–33. doi: 10.1111/j.1365-4632.2010.04598.x. [DOI] [PubMed] [Google Scholar]
- 33.Van Voorhees AS, Stein Gold L, Lebwohl M, et al. Efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis of the scalp: Results of a phase 3b, multicenter, randomized, placebo-controlled, double-blind study. J Am Acad Dermatol. 2020;83(1):96–103. doi: 10.1016/j.jaad.2020.01.072. [DOI] [PubMed] [Google Scholar]
- 34.Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3):418–31. doi: 10.1016/j.jaad.2016.11.042. [DOI] [PubMed] [Google Scholar]
- 35.Ohtsuki M, Kubo H, Morishima H, Goto R, Zheng R, Nakagawa H. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J Dermatol. 2018;45(9):1053–62. doi: 10.1111/1346-8138.14504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Thaçi D, Pinter A, Sebastian M, et al. Guselkumab is superior to fumaric acid esters in patients with moderate-to-severe plaque psoriasis who are naive to systemic treatment: results from a randomized, active-comparator-controlled phase IIIb trial (POLARIS) Br J Dermatol. 2020;183(2):265–75. doi: 10.1111/bjd.18696. [DOI] [PubMed] [Google Scholar]
- 37.Reich K, Papp KA, Blauvelt A, et al. Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial. Lancet. 2021;397(10273):487–98. doi: 10.1016/s0140-6736(21)00125-2. [DOI] [PubMed] [Google Scholar]
- 38.Gordon KB, Foley P, Krueger JG, et al. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet. 2021;397(10273):475–86. doi: 10.1016/s0140-6736(21)00126-4. [DOI] [PubMed] [Google Scholar]
- 39.Lebwohl M, Tyring S, Bukhalo M, et al. Fixed Combination Aerosol Foam Calcipotriene 0.005% (Cal) Plus Betamethasone Dipropionate 0.064% (BD) is More Efficacious than Cal or BD Aerosol Foam Alone for Psoriasis Vulgaris: A Randomized, Double-blind, Multicenter, Three-arm, Phase 2 Study. J Clin Aesthet Dermatol. 2016;9(2):34–41. [PMC free article] [PubMed] [Google Scholar]
- 40.Okubo Y, Natsume S, Usui K, Muro M, Tsuboi R. Combination therapy using maxacalcitol and corticosteroid lotions preliminary to monotherapy with maxacalcitol lotion for scalp psoriasis. J Dermatolog Treat. 2014;25(1):34–7. doi: 10.3109/09546634.2012.687087. [DOI] [PubMed] [Google Scholar]
- 41.Bahraini P, Rajabi M, Mansouri P, Sarafian G, Chalangari R, Azizian Z. Turmeric tonic as a treatment in scalp psoriasis: A randomized placebo-control clinical trial. J Cosmet Dermatol. 2018;17(3):461–66. doi: 10.1111/jocd.12513. [DOI] [PubMed] [Google Scholar]
- 42.Jury CS, McHugh L, Shankland GS, Burden AD. A randomized, placebo-controlled trial of oral itraconazole in scalp psoriasis. J Dermatol Treat. 2000;11(2):85–89. doi: 10.1080/09546630050517469. [DOI] [Google Scholar]
- 43.Rich P, Gooderham M, Bachelez H, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to-treat nail and scalp psoriasis: Results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2) J Am Acad Dermatol. 2016;74(1):134–42. doi: 10.1016/j.jaad.2015.09.001. [DOI] [PubMed] [Google Scholar]
- 44.Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405–17. doi: 10.1016/j.jaad.2016.11.041. [DOI] [PubMed] [Google Scholar]
- 45.Bergstrom KG, Arambula K, Kimball AB. Medication formulation affects quality of life: a randomized single-blind study of clobetasol propionate foam 0.05% compared with a combined program of clobetasol cream 0.05% and solution 0.05% for the treatment of psoriasis. Cutis. 2003;72(5):407–11. [PubMed] [Google Scholar]
- 46.Stein Gold L, Papp K, Pariser D, et al. Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2022;86(1):77–85. doi: 10.1016/j.jaad.2021.07.040. [DOI] [PubMed] [Google Scholar]
- 47.Camela E, Ocampo-Garza SS, Cinelli E, Villani A, Fabbrocini G, Megna M. Therapeutic update of biologics and small molecules for scalp psoriasis: a systematic review. Dermatol Ther. 2021;34(2):e14857. doi: 10.1111/dth.14857. [DOI] [PubMed] [Google Scholar]
- 48.Takeda K, Arase S, Takahashi S. Side effects of topical corticosteroids and their prevention. Drugs. 1988;36(Suppl 5):15–23. doi: 10.2165/00003495-198800365-00005. [DOI] [PubMed] [Google Scholar]
- 49.Fotiadou C, Lazaridou E, Sotiriou E, Kyrgidis A, Apalla Z, Ioannides D. Scalp psoriasis and biologic agents: a retrospective, comparative study from a tertiary psoriasis referral centre. J Eur Acad Dermatol Venereol. 2016;30(12):2091–96. doi: 10.1111/jdv.13780. [DOI] [PubMed] [Google Scholar]
- 50.Feldman SR. Treatment of psoriasis in adults. 2023 [Google Scholar]
- 51.Hoffman MB, Hill D, Feldman SR. Current challenges and emerging drug delivery strategies for the treatment of psoriasis. Expert Opin Drug Deliv. 2016;13(10):1461–1473. doi: 10.1080/17425247.2016.1188801. [DOI] [PubMed] [Google Scholar]
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