Table 3.
Principal recent clinical trials regarding treatment of patients with GPP and PPP/PPPP.
| Drug | References | Study Type (Randomization Ratio, If Applicable) | Identifier Number, If Applicable | Participants * | Details of Treatment (AT in Placebo-Controlled Studies) | Main Efficacy Results (Primary Outcome, If Applicable) |
|---|---|---|---|---|---|---|
| Spesolimab (anti-IL-36 receptor mAb) |
[126] | Phase 1, proof-of-concept, OL, SA | ClinicalTrials.gov NCT02978690 | 7 patients with GPP flare | Single intravenous dose at 10 mg/kg | At week 4, GPPGA score of 0 or 1 (“clear” or “almost clear”) in all patients, and mean GPPASI improvement from baseline of 79.8% |
| [127] | Phase 2a, DB, RPC (1:1:1) |
ClinicalTrials.gov NCT03135548 | 59 PPP patients | 900 mg or 300 mg intravenously every 4 weeks at Day 1, 29, 57 and 85 | PPPASI50 response at week 16 in 31.6% in each of the two AT groups vs. 23.8% in the placebo group (N.S.) | |
| Adalimumab (anti-TNF-alpha mAb) |
[128] | Phase 3, OL, SA | ClinicalTrials.gov NCT02533375 | 10 Japanese GPP patients | 80 mg s.c. at week 0 followed by 40 mg every other week: last dose at week 50 (escalation to 80 mg every other week at week 8 or later, if necessary) | Clinical response [remission (TSS 0) or improvement (reduction of ≥1 point from a baseline TSS of 3 or ≥2 points from a baseline TSS of ≥4)] at week 16 in 70% (n = 10) |
| Infliximab (anti-TNF-alpha mAb) |
[129] | Phase 3, OL, SA SPREAD study |
ClinicalTrials.gov NCT01680159 | 7 Japanese GPP patients with loss of efficacy to standard-dose maintenance therapy | Escalation to 10 mg/kg (intravenous infusion) every 8 weeks | Severity graded as mild in 71% and moderate in 29% at week 0, and mild in all patients at weeks 24 and 40 |
| Secukinumab (anti-IL-17A mAb) |
[130] | Phase 3, OL, SA | ClinicalTrials.gov NCT01952015 | 12 Japanese GPP patients | 150 mg s.c. at week 0, 1, 2, 3 and 4, and then every 4 weeks until week 52 (300 mg in 2 non-responders) | At week 16, treatment success in 83.3% (n = 10) [CGI of “very much improved” (n = 9) or “much improved” (n = 1)] |
| [131] | Phase 3b, DB, RPC (1:1:1) 2PRECISE study |
ClinicalTrials.gov NCT02008890 | 237 patients with moderate-to-severe PPPP | 300 mg or 150 mg s.c. at weeks 0, 1, 2, 3, and 4, and then every 4 weeks until week 52 | At week 16, PPPASI75 response in 26.6% of patients with high-dose AT, 17.5% with low-dose AT and 14.1% of patients who received placebo (N.S.) | |
| [132] | Extension period for patients with meaningful clinical response after completion of the 2PRECISE study | ClinicalTrials.gov NCT02008890 | 94 PPPP patients in total |
Extension of AT after week 52 up to 148 weeks | At week 148, PPPASI75 response rates increased in all groups, with similar levels for placebo/low-dose AT (75%), placebo/high-dose AT (77.8%), and initial high-dose AT (78.3%), and 100% responders in the initial low-dose AT group | |
| Ixekizumab (anti-IL-17A mAb) |
[133,134] | Phase 3, OL, SA UNCOVER-J study |
ClinicalTrials.gov: NCT01624233 | 5 Japanese GPP patients | 160 mg at week 0, 80 mg every 2 weeks from week 2 to week 12, 80 mg every 4 weeks thereafter up to week 244 | GIS of “resolved” or “improved” in all patients from week 12 onward |
| Brodalumab (anti-IL-17 receptor A mAb) |
[135] | Phase 3, OL, SA | ClinicalTrials.gov NCT01782937 | 12 Japanese GPP patients | 140 mg s.c. at weeks 0, 1 and 2, and then every 2 weeks until week 52 (escalation to 210 mg at week 4 and beyond, if necessary) | CGI of “improved’ or ‘remission’ in 83.3% at week 12 and 91.7% at week 52 |
| Guselkumab (anti-IL-23p19 mAb) |
[136] | Phase 3, OL, SA | ClinicalTrials.gov NCT02343744 | 10 Japanese GPP patients (9 evaluable) | 50 mg s.c. at weeks 0, 4 and every 8 weeks until week 52 (beginning at week 20, escalation to 100 mg every 8 weeks, if necessary) | At week 16, treatment success in 77.8% [CGI of “very much improved” in 2 patients, “much improved” in 2, and “minimally improved” in 3 subjects) |
| [137] | Phase 2, proof-of-concept, DB, RPC (1:1) | ClinicalTrials.gov NCT01845987 | 49 Japanese PPP patients | 200 mg s.c. at weeks 0 and 4 | Reduction in mean PPSI total score from baseline at week 16 −3.3 in the AT group vs. −1.8 in the placebo group (difference in LS mean, −1.5; 95% CI, −2.9 to −0.2; p = 0.03) | |
| [138] | Phase 3, DB, RPC (1:1:1) | ClinicalTrials.gov NCT02641730 | 159 Japanese patients with refractory PPP | 100 mg or 200 mg s.c. at weeks 0, 4, and 12, and every 8 weeks thereafter | At week 16, LS mean change in PPPASI score from baseline −15.3 (p < 0.001) for the low-dose AT group and −11.7 (p = 0.02) for high-dose AT group vs. −7.6 for the placebo group | |
| [139] | Extension period | ClinicalTrials.gov NCT02641730 | 133 patients completed the study at week 84 |
Treatment until week 60. At week 16, re-randomization from the placebo group to AT 100 or 200 mg (1:1 ratio) |
Continuous improvements in the PPPASI and PPSI total scores through week 60 and sustained in the observational phase across all treatment groups, including the placebo-crossover groups | |
| Anakinra (recombinant IL-1 receptor antagonist) |
[140] | Phase IV DB, RPC (1:1) APRICOT study |
EudraCT 2015-003600-23 | 64 PPP patients | 100 mg/0.67 mL s.c. daily for 8 weeks | At week 8, mean difference in PPPASI -1.65 (95% CI −4.77 to 1.47) in favour of AT (but N.S.) |
| 308-nm Excimer laser | [141] | Randomized, comparative | - | 77 Chinese PPP patients | Three times weekly for 8 weeks, with different doses: low, medium or high (2-fold, 4-fold, or 6-fold of MED as initial dose, respectively) | Significant reduction of PPPASI score compared with the baseline in all groups, with a greater reduction in the high dose group |
| UVA1 | [142] | Assessor-blinded, SA | - | 62 Chinese PPP patients | Three times weekly for up to 30 sessions | At 30 sessions, PPPASI50 and PPPASI75 responses in 90.3% and 72.6% of patients, respectively |
| UVA1 or NB-UVB | [143] | Assessor-blinded, RC (random assignment according to a left-right randomization table) |
- | 66 Chinese PPP patients | Three times weekly for up to 30 sessions | At the end of the treatment period, significant improvement of the PPPASI score compared with baseline in both groups (p < 0.05), and mean PPPASI reduction of 6.0 (SD 2.4) in the UVA1-treated group vs. 4.4 (SD 1.4) for NB-UVB (p < 0.05) |
| FAE-PUVA or Re-PUVA | [144] | Assessor-blinded, RC (1:1) | Clinicaltrials.gov NCT00811005 | 21 PPP patients | Dimethylfumarate up to a 720 mg/day or acitretin 50 mg/day for 2 weeks, then addition of PUVA thrice weekly for 12 weeks or after achievement of the PPPASI90. In the maintenance 24-week phase, use of half of the last drug dose or until significant relapse, followed by another 24 weeks without any treatment |
At the end of clearing phase, PPPASI90 response rates of 81.8% in the FAE-PUVA group and 90% in the Re-PUVA group (N.S.). After the maintenance phase, PPPASI90 rates of 90.9% in the FAE-PUVA arm and 70% in the Re-PUVA group (N.S.). During the follow-up period, PPPASI90 rates of 90.9% in the FAE-PUVA group and 50% in the Re-PUVA group (p = 0.038) |
| Alitretinoin | [145] | Phase 2, DB, RPC (2:1) | Clinicaltrials.gov NCT01245140 | 33 patients with PPP refractory to topical therapy and standard skin care | 30 mg once daily for up to 24 weeks | Mean percentage change from baseline in PPPASI at week 24 (or last visit): −45.2 (SD 32.8) in the AT group vs. −44.6 (SD 45.9) in the placebo group (N.S.) |
| Apremilast | [146] | Phase 2, OL, SA APLANTUS study |
Clinicaltrials.gov NCT04572997 | 21 subjects with moderate-to-severe PPP | Treatment for 20 weeks (final dose of 30 mg twice daily, gradually increased from 10 mg/day) | Median PPPASI improvement at week 20 compared to baseline of 57.1% (p < 0.001) |
| Tofacitinib | [147] | OL, SA, pilot study (primary endpoint: response of nail lesions) | ChiCTR1900025941 | 13 Asian patients with SAPHO syndrome accompanied by nail lesions and active PPP | 5 mg, twice daily, for 12 weeks | At week 12, median improvement in PPPASI score of 71% (p < 0 .001) |
| Pamidronate disodium | [148] | OL, SA Assessment of PPP in a cohort of 30 patients with SAPHO syndrome |
Clinicaltrials.gov NCT02544659 (original study in SAPHO syndrome) | 25 Chinese PPP patients with SAPHO syndrome | 1 mg/kg/day intravenously for 3 days at baseline and again 3 months later | PPPASI reduction > 50% in a total of 13 and 11 patients after the first and second treatment, respectively |
| Maxacalcitol ointment | [149] | Phase 3, DB, RPC (1:1) | - | 188 Japanese patients with moderate-to-severe PPP | 2 applications per day for 8 weeks | Significant decrease in the total score of skin findings in the AT group vs. placebo at week 8 or at the last visit (p < 0.0001) |
| Betamethasone butyrate propionate ointment alone or combined with maxacalcitol ointment | [150] | RC (left-right comparison) |
- | 29 patients with PPP (27 evaluable) | Betamethasone ointment applied once daily or betamethasone ointment + maxalcitol ointment (both applied once daily) for 8 weeks | Improvement rates in skin symptoms at week 8 significantly higher with the combination therapy than with the monotherapy |
Full-text articles in English published from 1 January 2016 until 1 October 2021 were selected in the PubMed database. * For studies that recruited patients with different forms of psoriasis, only details of PP patients are reported. AT: active treatment; CGI: clinical global impression of improvement; CI: confidence interval; DB: double blind; GIS: Global Improvement Score; FAE-PUVA: fumaric acid ester + PUVA; GPP: generalized pustular psoriasis; GPPGA: Generalized Pustular Psoriasis Physician Global Assessment; GPPASI: Generalized Pustular Psoriasis Area and Severity Index; IL: interleukin; LS: least squares; mAb: monoclonal antibody; MED: minimal erythema dose; NB-UVB: narrowband ultraviolet B; N.S.: no statistically significant difference; OL: open label; PPP: palmoplantar pustulosis; PPPASI: Palmoplantar Pustulosis/Pustular Psoriasis Area and Severity Index; PPPASI50: at least 50% decrease from baseline of the PPPASI; PPPASI75: at least 75% improvement from baseline in PPPASI; PPPASI90: at least 90% reduction of the baseline PPPASI; PPSI: Palmoplantar Pustulosis Severity Index; PPPP: palmoplantar pustular psoriasis; PUVA: psoralen + ultraviolet A; RC: randomized controlled; Re-PUVA: retinoid + PUVA; RPC: randomized placebo-controlled; SA: single arm; s.c.: subcutaneously; SAPHO: synovitis, acne, pustulosis, hyperostosis, and osteitis; SD: standard deviation; TNF: tumor necrosis factor; TSS: total skin score; UVA: ultraviolet A.