Table 1.

Overview of studies on targeted treatment in palmoplantar pustulosis

Study	Study type	Subjects (N)	Treatment	Treatment duration	Outcome	Adverse events/comment
ADA (TNF inhibitor)
Philipp et al. [107]	Retrospective study	2 PPPP	Case 1: SC ADA 40 mg every 2 wk (without a loading dose) + MTX 5–15 mg every wk	Case 1: 36 mo	Case 1: After 6 mo symptom-free, good clinical appearance until year 3; PGA 1 to PGA 0	Case 1: Recurrent oral candidiasis (improved after MTX dosage reduction)
			Case 2: SC ADA 40 mg every 10 days + ACI 25 mg/day		Case 2: concomitant ulcerative colitis. Good response. PGA 3 to PGA 1	Case 2: Headache
ANA (IL-1 inhibitor)
Tauber et al. [116]	Case report	2 PPPP	SC ANA 100 mg daily	Case 1: 3 mo	Partial clinical outcome Case 1: PPPASI 28.5 at baseline and 20.7 at wk 6. Improvement noticed in 2nd wk after treatment onset. Relapse after 3 mo
				Case 2: 2 mo	Case 2: PPPASI 19.2. Treatment was stopped in 2nd mo because of fever. One mo after interruption PPPASI was 13	Case 2: Acute fever
APR (PDE4 inhibitor)
Mikhailitchenko et al. [113]	Retrospective study	8	APR 30 mg BID. 2 pts + UST; 1 pt + MTX	4–30 mo	Response in all 8 pts as either monotherapy or combination therapy (MTX or UST)	Minimal AEs reported in 3/8 (loose stool); 1 pt more severe AEs
Alomran et al. [110]	Retrospective study	4 PPPP	APR + IXE (in 1 pt + MTX)	4–8 mo	Case 1: PPPGA 2 at baseline, PPPGA 3 on anti-IL-17A and PPPGA 1 on combination therapy Case 2: PPPGA 4 at baseline, PPPGA 3 on anti-IL-17A, PPPGA 1 on combination therapy Case 3: PPPGA 2 at baseline, PPPGA 3 on anti-IL-17A, PPPGA 0 on combination therapy Case 4: PPPGA 1 at baseline, PPPGA 0 on combination therapy	Case 1. Folliculitis, transient nausea and diarrhea
Eto et al. [111]	Case report	3	PO	8 mo	After 2 wk, all pts achieved near-complete symptom resolution. DLQI score showed significant improvement	One mild epigastric distress
BRO (IL-17 receptor inhibitor)
Pinter et al. [109]	Case series	4	BRO 210 mg at wk 0, 1; then every 2 wk	4–44 wk	Three of four pts showed lack of efficacy; one had worsening of PPP. One experienced moderate improvement but AEs led to discontinuation Case 1: PPPASI 10.5 at the start and PPPASI 12.0 at end Case 2: PPPASI 5.9 at the start and PPPASI 8.6 at end Case 3: PPPASI not done Case 4: PPPASI 12.8 at start and 6.3 at end	Case 1: worsening of plaque psoriasis Case 4: Worsening of arthritis, bad taste
ETA (TNF inhibitor)
Bissonnette et al. [106]	Randomized, prospective study	15	ETA 50 mg SC twice wkly for 24 wk vs. PL for 12 wk, then 50 mg SC twice wkly for 12–24 wk	24 wk	At wk 24: significant decrease in median PPPASI score for pts receiving ETA vs. PL (p = 0.038, n = 10)	Most common AEs: injection site reaction, headache, common cold
GUS (IL-23 inhibitor)
Terui et al. [104]	Randomized, double-blind, PL-controlled clinical trial	41 of 49	GUS 200 mg SC vs. PL at wk 0 and 4	24 wk	At wk 16, PPPASI scores reduced (− 5.65; 95% CI − 9.80 to − 1.50; p = 0.009). Wk 24 − PPPASI-50 responders (GUS, 16/25 [64%]; PL 8/24 [33%])	14 (29%) nasopharyngitis, 3 (6%) headache, 3 (6%) contact dermatitis, 3 (6%) injection site erythema
Terui et al. [105]	Phase III, multicenter, randomized, double-blind, PL-controlled study	159	GUS 100 mg SC, 200 mg SC vs. PL at wk 0, 4, 12 and every 8 wk	52 wk	At wk 16, (LSM change in PPPASI score from baseline was − 15.3 for GUS 100 mg vs. − 7.6 for PL; p < 0.001). PPPASI-75 response at wk 52 was reached in 55.6% of pts with GUS 100 mg and in 59.6% with GUS 200 mg	68 (43.3%) nasopharyngitis, 6 (3.8%) headache, 45 (28.7%) infections require oral or parenteral antibiotics treatment, 27 (17.2%) injection site reaction
HuMab 10F8 (IL-8 inhibitor)
Skov et al. [114]	Open-label multicenter study with single-dose dose-escalation setup	31 of 32	IV HuMab 0.15, 0.5, 1, 2, 4, and 8 mg/kg at 0, 4, 5, 6, 7 wk	8 wk	Reduction of 52.9% from baseline to wk 1 (p = 0.003); reduction of 55.9% from baseline to wk 8 (p = 0.0002)	Two serious AEs not related to HuMab 10F8; 25/31 pts (81%) had mild or moderate AEs (headache, fatigue, nasopharyngitis, nausea, hematuria)
SEC (IL-17A inhibitor)
Mrowietz et al. [108]	Multicenter, randomized, double-blind clinical trial; 2PRECISE	237 PPP	SEC 300 mg (n = 79) vs. 150 mg (n = 80) vs. PL (n = 78)	16 wk	At wk 16, PPPASI-75 response in 21/79 (26.6%) of pts with 300 mg vs. in 11/78 (14.1%) with PL (p = 0.0411) and in 14/80 (17.5%) with 150 mg (p = 0.5722). Primary endpoint of SEC superiority to PL at wk 16 not met	Nasopharyngitis and upper respiratory tract infections
UST (IL-12 and IL-23 inhibitor)
Bissonnette et al. [62]	Prospective randomized, PL-controlled study	13 PPP; 20 PPPP	UST 45 mg SC (< 100 kg) at wk 0 and 4 and subsequently at approximately 12‐wk intervals	16 wk	No statistically significant difference between UST and PL in PPPASI-50 at wk 16 in response for pts with PPPP (10%, 20%; p = 1.000) or PPP (20%, 37.5%; p = 1.000)	Cellulitis, pneumonia
Au et al. [98]	Single-center, open-label clinical trial	10 PPP, 10 hyperkeratotic PP	UST 45 mg SC (< 100 kg) or 90 mg SC (> 100 kg) wk 0, 4, 16	16 wk	At 16 wk: 7/20 (35%) achieved clinical clearance (palm-sole PGA of 0 or 1). But 6/9 (67%) subjects who received 90 mg vs. 1/11 (9%) who received 45 mg achieved clinical clearance (p = 0.02)	No serious AEs. 4/20 subjects (20%) developed an upper respiratory tract infection that resolved in < 2 wk. Two (10%) developed acne or acneiform eruptions and one acute bronchitis
Bertelsen et al. [102]	Observational descriptive study	5 PPP, 6 PPPP	UST 45 mg SC (< 100 kg) at wk 0 and 4 and subsequently at approximately 12‐wk intervals	> 3 years	Partial response (n = 6); complete resolution (n = 1); no response or aggravation of symptoms (n = 4)	Flu‐like symptoms, headache, fatigue
Hegazy et al. [100]	Retrospective study	9	UST 45 mg SC (< 100 kg) or 90 mg (> 100 kg). An increased dose to 90 mg every 12 wk was required in three pts to maintain efficacy	9 mo	Positive response initially in all pts about 4 wk after second dose. At wk 16, 5/9 pts experienced complete response; 4/9 experienced partial response (≥ 50% reduction in lesion counts)	One urinary tract infection
Morales-Múnera et al. [99]	Retrospective study	5 PPPP	UST 45 mg SC (< 100 kg) or 90 mg (> 100 kg) at 0, 4, then every 12 wk	11–23 mo	Positive response seen in all pts 2–3 wk after first dose. Complete resolution of PPPP achieved at wk 20	No AEs reported
Buder et al. [101]	Case series	9 PPPP	UST 45 mg SC (< 100 kg) or 90 mg SC (> 100 kg) at wk 0, 4, 12, 24	24–60 mo	Complete resolution (PPPASI 100; n = 2). 75% improvement of PPPASI (n = 4; 44.4%). Mean PPPASI improvement: 71.6% after 24 wk	No severe AEs; one local injection site reaction
Gerdes et al. [103]	Case series	4 PPPP	UST 45 mg SC (< 100 kg) or 90 mg SC (> 100 kg)	12 wk	Good but slow efficacy in only 1/4 pts with PPP. Treatment satisfactory in 2/4 pts. One pt had good clinical response of plaque psoriasis, but PPP lesions only slowly improved	No AEs reported

Inclusion criteria: recent studies and case reports involving two or more pts with PPP

ACI acitretin, ADA adalimumab, AE adverse events, ANA anakinra, APR apremilast, BID twice daily, BRO brodalumab, CI confidence interval, DLQI Dermatology Life Quality Index, ETA etanercept, GUS guselkumab, IL interleukin, IV intravenous, IXE ixekizumab, LSM least-squares mean, mo month(s), MTX methotrexate, PDE4 phosphodiesterase 4, PGA Physician Global Assessment, PL placebo, PO oral administration, PPP palmoplantar pustulosis, PPPASI Palmoplantar Pustulosis Area and Severity Index, PPPGA Palmoplantar Psoriasis Physician Global Assessment, PPPP palmoplantar pustular psoriasis, pt(s) patient(s), SC subcutaneous, SEC secukinumab, TNF tumor necrosis factor, UST ustekinumab, wk week(s)