Introduction
Methods
Eligibility Criteria
Study Selection and Data Extraction
Compliance with Ethics Guidelines
Results
Reference, type of study | Number of subjects | Treatment | Treatment duration | Outcome | Safety/comments |
---|---|---|---|---|---|
Adalimumab | |||||
Leonardi 2011 [14], Double-blind randomized placebo-controlled trial | 72 | 2:1 adalimumab 80 mg SC at week 0 and 40 mg SC q 2 weeks thereafter vs. placebo | 16 weeks | 30.6% (15) adalimumab-treated subjects achieved hfPGA of 0 or 1 at week 16 vs. 4.3% (1) placebo-treated subject (p = 0.01) | No AEs reported |
Alefacept | |||||
Myers 2005 [21], case report | 2 | Alefacept (15 mg IM once weekly) | 12 weeks | (1) complete resolution at 5 weeks; (2) improvement at 10 weeks, reduced scaling, redness, inflammation, plaque thickness | No AEs reported; 2 = some recurrence when alefacept stopped, requiring restarting treatment for 10 additional weeks |
Etanercept | |||||
Meyer 2011 [25], case report | 1 | Alitretinoin 30 mg PO daily + etanercept 50 mg SC weekly | 13 months | Marked reduction within 4 weeks, complete resolution in 8 weeks | No AEs reported |
Guselkumab | |||||
Blauvelt 2017 [15], VOYAGE1 RCT | 100 (subset of 837 psoriasis patients) | Guselkumab (2:1:2 randomization, 100 mg at week 0, 4, then q 8 weeks) or placebo to guselkumab (placebo weeks 0, 4, 12 then guselkumab weeks 16, 20 then q8 weeks), or adalimumab 80 mg week 0, then 40 mg week 1, then 40 mg q 2 weeks) | 16a, 24, or 48 weeksa
| At week 16, guselkumab 73.3% reached IGA 0/1 vs. adalimumab 55.8%, vs. placebo 14%; week 24, guselkumab IGA 0/1 78.9% vs. adalimumab 56.8%; week 48, guselkumab IGA 0/1 75.6% vs. adalimumab 62.1% | Overall cohort: Nasopharyngitis, URI, cellulitis (2 in adalimumab group), basal cell carcinoma (1 in guselkumab group), 2 myocardial infarctions |
Infliximab | |||||
Bissonnette 2011 [13], double-blind randomized placebo-controlled trial | 24 | 1:1 infliximab 5 mg/kg IV at week 0, 2, 6, 14, 22 vs. placebo at weeks 0, 2, 6, then infliximab at weeks 14, 16, 20 | 14a or 22 weeks | At week 14, 33.3% achieved m-PPPASI-75 and 66.7% achieved m-PPPASI-50 vs. 8.3% for either (p = 0.317 and p = 0.009); 50.3% reduction in mean surface area vs. 14.9% increase with placebo | 3 SAEs: 1 hepatitis, 1 cellulitis, 1 sternum fracture |
Brunasso 2012 [33], case series | 5 | Infliximab 5 mg/kg at weeks 0, 2, 6, and every 8 weeks thereafter | 30 weeks | At week 14, mean m-PPPASI improved 27.69%; at week 30, mean m-PPPASI improved 41.2% | No AEs reported; compared changes in m-PPPASI with PASI: PASI improved 86.8% and 89.11% at weeks 14 and 30, respectively |
Ixekizumab | |||||
Menter 2017 [17], UNCOVER RCT | 206 | Ixekizumab (1:1:1 randomization, 160 mg at week 0, 80 mg every 2 or 4 weeks); etanercept (2:2:2:1 randomization, 160 mg ixekizumab at week 0, then 80 mg every 2 or 4 weeks, 50 mg etanercept twice weekly) | 12a, 48, or 60 weeks | At week 12, PPASI improvement of 80% with ixekizumab vs. placebo (28.1%) or vs. etanercept (53%) (p < 0.05 for all comparisons) Greater PPASI-50 improvement with ixekizumab (80%) vs. placebo (32.9%) or vs. etanercept (67.8%). Greater PPASI-75 improvement with ixekizumab (70%) vs. placebo (18.8%) or vs. etanercept (44.1%), (p < 0.05 for all comparisons) | No AEs reported |
Secukinumab | |||||
Gottlieb 2017 [16], GESTURE RCT | 137 | Secukinumab (1:1:1 randomization, 300 mg, 150 mg or placebo) | 16 weeks | PPIGA 0 (clear) or 1 (minimal): 33.3% with 300 mg regimen, 22.1% with 150 mg regimen, 1.5% on placebo (p < 0.001 and p = 0.002, respectively vs. placebo). DLQI 0/1 higher w secukinumab 300 mg (26.6%) and 150 mg (16.9%) vs. placebo (1.5%), p < 0.0001 and p < 0.005 | SAEs: 150 mg 5.9%, 300 mg 2.9%, placebo 2.9%; AEs (40): Headache (17), naropharyngitis (11), URI (10), Candida (3) |
Paul 2014 [18], RCT | 103 (46 patients in early regimen) | Secukinumab (1:2:2:1 randomization, 150 mg SC of either single (week 0), monthly (weeks 0, 4, 8), early (weeks 0, 1, 2, 4) or placebo) | 12 weeks | IGA response of 0 (clear) or 1 (minimal) + improvement of ≥ 2 points; Early regimen response: 54.0% | No AEs reported |
Ustekinumab | |||||
Heinecke 2013 [41], case series | 2 (subset of 22 psoriasis patients) | Ustekinumab 45 mg or 90 mg SC at weeks 0, 4, and every 12 weeks thereafter + acitretin PO | Not described | Both patients demonstrate “excellent control” with only mild scaling | No AEs related to PP subjects reported |
Nuno-Gonzalez 2012 [42], case report | 1 | Ustekinumab 45 mg SC at weeks 0, 4, and every 12 weeks thereafter | 12 months | Complete resolution at 16 weeks, maintained clear at 12 months | No AEs reported |
Bulai Livideanu 2010 [43], case series | 2 | Ustekinumab 45 mg and 90 mg SC respectively at weeks 0, 4, and every 12 weeks thereafter | (1) 7 months (2) 4 months | (1) Dramatic improvement at 7 months, localized PPASI improved by 85%; (2) Palms cleared at 1 month, good clinical improvement and localized PPASI improved 65% at 4 months | No AEs reported |
Reference, type of study | Number of subjects | Treatment | Treatment duration | Outcome | Safety/comments |
---|---|---|---|---|---|
Adalimumab | |||||
Ghate 2009 [24], case report | 1 | Adalimumab 40 mg SC q 2 weeks | 6 months | At week 16, BSA decreased from 4 to 1%, resolution of PsA symptoms; 8 months after d/c, no joint symptoms or PP | No SAEs reported; mild, diffuse scalp alopecia (leading to d/c at 6 months) |
Etanercept | |||||
Ahmad 2007 [27], case series | 1 (subset of 49 psoriasis patients) | Etanercept 25 mg or 50 mg SC BIW | Total mean 58.2 weeks | Failed | Unclear |
Floristan 2011 [28], case report | 1 | Etanercept 0.4 mg/kg SC BIW for 8 months increased to 0.6 mg/kg SC BIW | 12 months | Slow but progressive improvement over first month; at 12 months “striking improvement” of plantar lesions | No AEs reported |
Kitamura 2009 [30], case report | 1 | Etanercept 50 mg SC BIW + efalizumb 80 mg weekly | ≥ 11 months | Psoriasis and PsA “very well- controlled” (but pustular PP not responsive to etanercept alone) | 1 SAE: reactivation TB |
Infliximab | |||||
Kamili 2011 [35], case series | 6 (subset of 120 psoriasis patients) | Infliximab 5 mg/kg IV at weeks 0, 2, and 6 and every 8 weeks thereafter | At least 1 year | 2 patients with “complete responses” | Unclear |
Wozel 2008 [37], case report | 1 | Infliximab 5 mg/kg IV at week 0, 2, and 6 and every 8 weeks thereafter | 8 months | “Marked improvement” 4 days after staring infliximab, with “severe” relapse at 8 months | No SAEs reported |
Ahmad 2006 [39], case series | 1 (series of 12 psoriasis patients) | Infliximab 5 mg/kg IV at week 0, 2, 6 and every 8 weeks thereafter | Not described | Excellent improvement after third infusion | No SAEs reported; discontinued due to elevated liver function tests |
Ustekinumab | |||||
Morales-Munera 2013 [45], case series | 5 | Ustekinumab 45 mg SC at weeks 0, 4, and every 12 weeks thereafter | Mean 15.2 months, range 11–23 months | All patients with positive response 2-3 weeks after first dose, all with complete resolution at week 20 maintained to date with no flares | No AEs reported |
Buder 2016 [51], case series | 9 | Ustekinumab (45 mg if < 100 kg body weight, 90 mg if > 100 kg body weight at weeks 0, 4, 12, 24) | 24 weeks | After 24 weeks, 44.4% reached PPASI-75, 22.2% reached PPASI-100, PPASI improvement was 71.6%; goal: improve PPASI by 75% after 12 weeks or improve DLQI by 5 points | No AEs reported; recurrence in 1 patient required stopping treatment and switching to golimumab with improvement |
Reference, type of study | Number of subjects | Treatment | Treatment duration | Outcome | Safety/comments |
---|---|---|---|---|---|
Adalimumab | |||||
Olazagasti 2017 [22], retrospective cohort study | 8 | Adalimumab, etanercept, infliximab | 1996–2013 | Partial response to adalimumab (2; no response to adalimumab (2); no response to etanercept (3); partial response to infliximab (1) | No AEs reported |
He 2012 [23], case report | 1 | Adalimumab 40 mg SC q 2 weeks + methotrexate 15 mg weekly | 1 month | Response of PP not described | No SAEs reported; acneiform eruption, alopecia areata, and urticaria after third injection leading to d/c |
Etanercept | |||||
Bissonnette 2008 [12], Double-blind randomized placebo-controlled trial | 15 | 2:1 etanercept 50 mg SC BIW week 0-24 vs. placebo weeks 0–12 then etanercept 50 mg SC BIW weeks 12–24 | 6 vs. 3 months | Significant decrease in median PPPASI at week 24 in etanercept group; no significant difference between groups at 12 weeks (primary end point) (p = 0.426) | No SAEs reported; Decreased PPPASI in 3/3 nonsmokers (increased PPPASI in 4/7 smokers) in etanercept group at 12 weeks |
Lopez-Estebaranz 2010 [29], case report | 1 | Etanercept 50 mg SC BIW for 12 weeks, then weekly for 12 weeks | 6 months | At week 12, complete resolution; maintained clearance for 6 months after discontinuation of etanercept | No AEs reported |
Kasche 2007 [31], case report | 1 | Etanercept 25 mg SC BIW | 7 months | “Sudden and dramatic improvement” at 2 weeks; restarted due to flare after d/c with “dramatic and rapid improvement” after 1 week | No SAEs reported |
Weinberg 2003 [32], Case report | 1 | Etanercept 25 mg SC BIW | 19 weeks | At 19 weeks, “almost total clearing” of hands with “mild to moderate scaling” of feet, resolution of PsA symptoms | No AEs reported |
Abourazzak 2014 [49], case report | 1 | Etanercept 25 mg twice weekly | 12 months | Resolved; “good improvement within the first month” | No AEs reported |
Infliximab | |||||
Burgemeister 2012 [20], case series | 2 (subset of 3 PPP) | Infliximab (5 mg/kg q 8 weeks) | Not reported | complete resolution | No AEs reported |
Aljuhani 2015 [50], case series | 2 (subset of 20 PPP) | (1) Infliximab; (2) adalimumab, etanercept | (1) 3 years; (2) 9 months | (1) completely resolved; (2) no response to adalimumab, then switched to etanercept with no response | No AEs reported |
Yawalkar 2009 [36], Case report | 1 | Infliximab 5 mg/kg IV at weesk 0, 2, 6; then at week 14 adalimumab 40 mg SC q 2 weeks then 40 mg SC weekly | 6 weeks infliximab, then ≥ 3 months adalimumab | “Marked improvement” at 2 weeks with recurrence at week 14; slower but satisfactory clinical response with adalimumab | 1 SAE: infusion related reaction with polyarthalgia, myalgia and fever at week 6 leading to discontinuation |
Fairhurst 2008 [38], Case report | 1 | Infliximab 5 mg/kg IV at weesk 0, 2, 6 | 6 weeks | “Dramatic improvement” after first 2 infusions, “deterioration” after third infusion | 1 SAE: autoimmune hepatitis |
Barland 2003 [40], Case report | 1 | Infliximab 5 mg/kg IV monthly months 0–4, infliximab 10 mg/kg IV monthly months 5-6, then infliximab 10 mg/kg IV monthly + methotrexate 7.5 mg PO weekly | Not reported | Initial “dramatic response” followed by relapse; addition of methotrexate led to “virtually absent” lesions within 2 weeks with “lasting remission” | No AEs reported |
Ustekinumab | |||||
Torre 2017 [53], case report | 1 | Adalimumab (40 mg SC every other week × 4 months then 40 mg weekly × 6 months) + mycophenolate + Ustekinumab (90 mg on day after 10 months at days 1, 28, then q 3 months) | 14 months | 95% clearance after 14 months | No AEs reported |
Pinto-Almeida 2013 [46], Case report | 1 | Ustekinumab 45 mg SC at weeks 0, 4, and every 12 weeks thereafter | 12 months | Clinical improvement noted at 3 weeks and clearance achieved at 16 weeks; sustained response at 12 months | No AEs reported |
de Unamuno-Bustos 2011 [47], Case report | 1 | Ustekinumab 45 mg SC q 12 weeks | 8 months | After 2 doses “almost complete clearance”; remained clear of lesions at 8 months | No AEs reported |
Gerdes 2010 [48], case series | 4 | Ustekinumab 45 mg or 90 mg (if ≥ 100 kg) SC q 12 weeks | 2 months to unclear | Failure in 2 subjects (1 and 2); slow improvement in 1 subject (palms clear but soles still affected at 3 months); decreased pustules and involved area of both soles at 3 months in 1 subject | No AEs reported |
Reference, type of study | Number of subjects | Treatment | Treatment duration | Outcome | Safety/comments |
---|---|---|---|---|---|
Adalimumab | |||||
Richetta 2012 [19], open label study | 11 (hyperkeratotic or pustular PP; variant not reported) | Adalimumab (40 mg q 2 weeks) | 12 weeks | PGA improvement 54.5%, mean PGA: 1.09, PGA 0 36.1%; DLQI improvement: 72.3%, mean DLQI: 7.45, ≥ 50% DLQI improvement 45.5% | No AEs reported |
Anakinra | |||||
Tauber 2014 [52], case report | (1) pustular PP, (2) hyperkeratotic PP | Anakinra (100 mg SC) | (1) 3 months; (2) 1 month | (1) Partial response to PPASI 20.7 and DLQI 13 at 2 weeks but relapsed at 3 months, stopped due to lack of efficacy/recurrence (2) Partial response to PPASI 13.5 at 1 mo, stopped due to fever without cause | (1) relapse of pustular lesions; (2) AE of fever |
Etanercept | |||||
Spuls 2003 [26], Case series | 1 (etanercept) and 1 (infliximab) (subset of 26 patients with PP; hyperkeratotic or pustular variant not reported) | (1) Etanercept; (2) infliximab | Not described | (1) Complete resolution (2) Complete resolution | No AEs reported |
Infliximab | |||||
Di Lernia 2010 [34], Case series | 3 (hyperkeratotic PP), 1 (PPP) | Infliximab 5 mg/kg IV at weesk 0, 2, 6 and every 8 weeks thereafter | 10–16 months | At 16 weeks, (1) PPPAS- 100; (2) and (3) PPPASI-75; (4) PPPASI-50 | 1 SAE: infusion-related urticarial reaction in patient 2 at week 46 leading to discontinuation |
Ustekinumab | |||||
Bissonnette 2013 [11], Double-blind randomized placebo-controlled trial | 10 (pustular PP), 5 (PPP) | 1:1 ustekinumab 45 mg SC at weeks 0, 4, and 16 vs. placebo at weeks 0 and 4, then ustekinumab 45 mg SC at weeks 16 and 20 | 28 weeks (primary endpoint at week 16) | At week 16, 10% of subjects with pustular PP achieved PPPASI-50 vs. 20% in placebo group (p = 1.00); 20% of subjects with PPP achieved PPPASI-50 vs. 37.5% in placebo group (p = 1.00) | No SAEs reported; 1 leg cellulitis (possibly related) and 1 pneumonia (unrelated) |
Au 2013 [10], Open-label prospective trial | 10 (hyperkeratotic PP), 10 (pustular PP) | Ustekinumab 45 mg for body weight < 100 kg, 90 mg for body weight ≥ 100 kg SC at weeks 0, 4, 16 | 16 weeks | At week 16, 35% (7/20) achieved clinical clearance, 60% (12) Palm-Sole PGA improved ≥ 2 points | No related SAEs reported; 67% receiving 90 mg achieved clinical clearance vs. 9% of those on 45 mg |
Bertelsen 2014 [54], Case series | 6 (pustular PP), 5 (PPP) | Ustekinumab 45 mg SC at weeks 0, 4, and every 12 weeks thereafter | Up to 44 months | Pustular PP: 1 Complete resolution (1), partial response (3), no response (1), progression (1); PPP: Partial response (3), no response (1), progression (1) | Flu-like symptoms, headache, fatigue (1); no difference reported in response between patients with palmoplantar pustular psoriasis and palmoplantar pustulosis |
Efficacy
Medication | Variant treated | Total number of cases | Cases in which patients demonstrated improvementa
| Serious adverse events |
---|---|---|---|---|
Adalimumab | 150 | 142 (94.7%) | No SAEs reported | |
Pustular PP [24] | 1 | 1 (100.0%) | No SAEs reported | |
7 | 2 (28.6%) | No SAEs reported | ||
Totalb
| 169 | 152 (89.9%) | ||
Alefacept | Hyperkeratotic PP [21] | 2 | 2 (100.0%) | No SAEs reported |
Pustular PP | 0 | 0 | ||
PPP | 0 | 0 | ||
Total | 2 | 2 (100.0%) | ||
Anakinra | Hyperkeratotic PP [52] | 1 | 1 (100.0%) | No SAEs reported |
Pustular PP [52] | 1 | 1 (100.0%) | No SAEs reported | |
PPP | 0 | 0 | ||
Total | 2 | 2 (100.0%) | ||
Etanercept | 60 | 41 (68.3%) | No SAEs reported | |
3 | 2 (66.7%) | Reactivation of latent TB | ||
23 | 13 (56.5%) | No SAEs reported | ||
Totalb
| 87 | 57 (65.5%) | ||
Guselkumab | Hyperkeratotic PP [15] | 100 | 90 (90.0%) | No SAEs reported |
Pustular PP | 0 | 0 | ||
PPP | 0 | 0 | ||
Total | 100 | 90 (90.0%) | ||
Infliximab | 32 | 24 (75.0%) | Cellulitis, hepatitis, infusion-related urticarial reaction | |
8 | 4 (50.0%) | |||
8 | 8 (100.0%) | Serum sickness-like infusion reaction, autoimmune hepatitis | ||
Totalb
| 49 | 37 (75.5%) | ||
Ixekizumab | Hyperkeratotic PP [17] | 206 | 170 (82.5%) | No SAEs reported |
Pustular PP | 0 | 0 | ||
PPP | 0 | 0 | ||
Total | 206 | 170 (82.5%) | ||
Secukinumab | 183 | 63 (89.1%) | 150 mg 5.9% SAE, 300 mg 2.9% SAE, placebo 2.9% SAEc
| |
Pustular PP | 0 | 0 | ||
PPP | 0 | 0 | ||
Total | 183 | 63 (89.1%) | ||
Ustekinumab | 15 | 13 (86.7%) | No SAEs reported | |
40 | 22 (55.0%) | No SAEs reported | ||
17 | 10 (58.8%) | No SAEs reported | ||
Total | 72 | 45 (62.5%) |