Table 1.
Randomized controlled trials (RCTs), cohort studies, case series, case reports on biologic therapy in HS.
| Drug | Study | Patients and Dose | Results |
|---|---|---|---|
| TNFα | |||
| Adalimumab | |||
| Kimball et al., 2016 [86] |
PIONEER I (n = 307) Adalimumab 40 mg/week s.c. (n = 153) Placebo s.c. (n = 154) PIONEER II (n = 326) Adalimumab 40 mg/week s.c. (n = 163) Placebo s.c. (n = 163) |
41.8% reached an HiSCR after 12 weeks 26.0% reached an HiSCR after 12 weeks 58.9% reached an HiSCR after 12 weeks 27.6% reached an HiSCR after 12 weeks |
|
| Zouboulis et al., 2019 [87] |
Open-label extension (OLE) trial (n = 151) Adalimumab 40 mg/week s.c. |
An HiSCR was achieved in 52% of patients at week 168 |
|
| Marzano et al., 2021 [25] |
Retrospective, real-life multicenter cohort study (n = 389) Adalimumab 160 mg s.c. at week 0, 80 mg at week 2 and 40 mg weekly starting at week 4 |
An HiSCR was achieved in 43.7% at week 16 and in 53.9% at week 52 |
|
| Infliximab | |||
| Grant et al., 2010 [89] |
Phase II placebo-controlled, double-blind RCT (n = 38) Infliximab 5 mg/kg i.v. at weeks 0, 2, 4, 6, 14 and 22 (n = 15) Placebo i.v. (n = 23) |
>50% decrease in HSSI reached in 27% at week 8 >50% decrease in HSSI reached in 5% at week 8 |
|
| Mekkes et al., 2008 [90] |
Long-term efficacy study (n = 10) Single course of infliximab (three intravenous infusions at weeks 0, 2 and 6) |
3/10 reported no relapse at 2-year follow-up 7/20 showed recurrence after 8.5 months |
|
| Oskardmay et al., 2019 [91] |
Retrospective cohort study (n = 52) Infliximab 10 mg/kg i.v. every 6 or 8 weeks |
67% of the patients achieved HS stability |
|
| Van Rappard et al., 2012 [92] |
Retrospective comparative study (n = 20) Infliximab i.v., 3 infusions of 5 mg/kg at weeks 0, 2 and 6 Adalimumab s.c. 40 mg every other week |
Average Sartorius score was reduced to 54% of baseline Average Sartorius score was reduced to 66% of baseline |
|
| Certolizumab pegol | |||
| Sand et al., 2015 [94] |
Retrospective study (n = 2) Certolizumab pegol 200 mg s.c. every 2 weeks |
Inefficacy with low dosage certolizumab |
|
| Holm et al., 2020 [95]; Esme et al., 2020 [95]; Wohlmuth-Wieser et al., 2020 [97] |
Case reports (n = 3) Certolizumab pegol 400 mg every other week or 200 mg every week |
Satisfactory response to certolizumab |
|
| Etanercept | |||
| Giamarellos-Bourboulis et al., 2008 [99] |
Prospective open-label phase II study (n = 10) Etanercept 50 mg s.c. once weekly for 12 weeks |
>50% decrease in disease activity in 7 patients at week 24 |
|
| Pelekanou et al., 2010 [100] |
Open-label phase II prospective trial (long term efficacy study) (n = 10) Etanercept 50 mg s.c. once weekly for 12 weeks |
3/10 did not report any disease recurrence 7/10 needed a second course of treatment, of which 5 had favorable response and 2 were not successfully treated |
|
| Cusack et al., 2006 [101] |
Open-label study (n = 6) Etanercept 25 mg s.c. twice weekly |
Mean reduction of 61% in self-reported disease activity at 24 weeks Mean reduction of 64% in DLQI scores at 24 weeks |
|
| Sotiriou et al., 2009 [102] |
Open label study (n = 4) Etanercept 25 mg s.c. twice weekly |
68.75% mean self-reported improvement at 6 months follow-up Mean reduction of 66.5% in DLQI scores at 6 months follow-up |
|
| Adams et al., 2010 [103] |
Randomized double-blind trial (n = 20) Etanercept s.c. 50 mg every other week (n = 10) Placebo s.c. (n = 10) |
No statistically significant difference between etanercept and placebo groups in PGA and DLQI |
|
| Golimumab | |||
| van der Zee et al., 2013 [105];; Tursi et al., 2016 [106]; Ramos et al., 2022 [107] |
Case reports (n = 4) Golimumab 50 mg s.c. every 4 weeks Golimumab 200 mg s.c. at week 0 and 100 mg every 4 weeks |
No clinical improvement Successful results with decrease in IHS4 |
|
| IL-17 | |||
| Secukinumab | |||
| Thorlacius et al., 2018 [120]; Schuch et al., 2018 [121]; Jørgensen et al., 2016 [122]; Głowaczewska et al., 2020 [123]; Villegas-Romero et al., 2020 [124]; Chiricozzi et al., 2020 [125] |
Case reports (n = 8) Secukinumab 300 mg s.c. weekly for 5 weeks, then every 4 weeks |
Successful response to secukinumab |
|
| Prussick et al., 2019 [126] |
Open-label, single-arm, pilot trial (n = 9) Secukinumab 300 mg s.c. weekly for 5 weeks, then every 4 weeks |
An HiSCR was achieved in 67% at week 24 |
|
| Casseres et al., 2020 [127] |
Open-label, single-arm pilot trial (n = 20) Secukinumab 300 mg s.c. weekly for 5 weeks, then for 9 patients 300 mg s.c. every 4 weeks, and for 11 patients 300 mg s.c. every 2 weeks |
An HiSCR was achieved in 70% at week 24 |
|
| Reguiaï et al., 2020 [128] |
Retrospective study (n = 20) Secukinumab 300 mg s.c. weekly for 5 weeks, then every 4 weeks |
An HiSCR was achieved in 75% at week 16 |
|
| Ribero et al., 2021 [129] |
Multicentric retrospective study (n = 31) Secukinumab 300 mg s.c. weekly for 5 weeks, then every 4 weeks |
An HiSCR was achieved in 41% at week 28 |
|
| NCT03713619 [130], NCT03713632 [131], NCT04179175 [132] | Phase III RCTs | Still ongoing | |
| Brodalumab | |||
| Tampouratzi et al., 2019 [134]; Yoshida et al., 2021 [135]; Arenbergerova et al., 2020 [136] |
Case reports (n = 3) Brodalumab 210 mg s.c. at weeks 0, 1 and 2, then 210 mg every 2 weeks |
Successful response to brodalumab |
|
| Frew et al., 2020 [137] |
Open-label cohort study (n = 10) Brodalumab 210 mg s.c. at weeks 0, 1 and 2, then 210 mg every 2 weeks |
100% achieved an HiSCR at week 12 |
|
| Frew et al., 2021 [138] |
Open-label cohort study (n = 10) Brodalumab 210 mg s.c. every 2 weeks |
100% achieved an HiSCR at week 4 |
|
| NCT04979520 [139] | Phase III RCTs | Still ongoing | |
| Ixekizumab | |||
| Odorici et al., 2020 [141]; Megna et al., 2020 [142]; Reardon et al., 2021 [143] |
Case reports (n = 3) Ixekizumab 160 mg s.c. at week 0; 80 mg at weeks 2, 4, 6, 8, 10 and 12 and then every 4 weeks |
Successful response to ixekizumab |
|
| Esme et al., 2022 [144] |
Case series (n = 5) Ixekizumab 160 mg s.c. at week 0; 80 mg at weeks 2, 4, 6, 8, 10 and 12 |
80% achieved an HiSCR at week 12 |
|
| Bimekizumab | |||
| Glatt et al., 2021 [146] |
Phase II, double-blind, placebo-controlled randomized clinical trial (n = 90) Bimekizumab 640 mg s.c. at week 0 and 320 mg every 2 weeks Placebo s.c. Adalimumab 160 mg at week 0, 80 mg at week 2 and 40 mg every week after |
57.3% achieved an HiSCR at week 12 26.1% achieved an HiSCR at week 12 60% achieved an HiSCR at week 12 |
|
| NCT04242446 [147]; NCT04242498 [148]; NCT04901195 [149] | Phase III RCTs | Still ongoing | |
| IL-12/23 | |||
| Ustekinumab | |||
| Montero-Vilchez et al., 2022 [158]; Valenzuela-Ubiña et al., 2020 [159] |
Case series (n = 20) Ustekinumab 90 mg s.c. every 2 months |
Successful response to ustekinumab |
|
| Blok et al., 2016 [115] |
Phase II open-label study (n = 17) Ustekinumab 45 mg s.c. if <90 kg and 90 mg s.c. if >90 kg at weeks 0, 4, 16 and 28 |
47% achieved an HiSCR at week 40 |
|
| Romaní et al., 2020 [160] |
Retrospective multicenter study (n = 14) Ustekinumab i.v. weight-adjusted induction dose (≤55 kg, 260 mg; 56–85 kg, 390 mg; ≥86 kg, 520 mg) then 90 mg s.c. every 8 weeks |
50% achieved an HiSCR at week 16 |
|
| Sánchez-Martínez et al., 2020 [161] |
Retrospective unicenter study (n = 6) Ustekinumab i.v. weight-adjusted induction dose (≤55 kg, 260 mg; 56–85 kg, 390 mg; ≥86 kg, 520 mg), then 90 mg s.c. every 8 weeks |
50% achieved an HiSCR at week 12 |
|
| IL-23 | |||
| Guselkumab | |||
| Kearney et al., 2020 [163]; Kovacs et al., 2019 [164]; Casseres et al., 2019 [165]; Berman et al., 2021 [166]; Jørgensen et al., 2020 [167] |
Case reports and case series (n = 14) Guselkumab 100 mg s.c. at week 0 and week 4 then every 8 weeks |
Successful response to Guselkumab |
|
| Melgosa Ramos et al., 2022 [168] |
Retrospective bicentric study (n = 11) Guselkumab 100 mg s.c. at week 0 and week 4 then every 8 weeks; then, for 6 patients, 100 mg every 6 weeks to maintain an HiSCR |
63.6% achieved an HiSCR at week 16 |
|
| Montero-Vilchez et al., 2020 [169] |
Case series (n = 4) Guselkumab 100 mg s.c. at week 0 and then every 4 weeks |
50% had moderate reduction in IHS4, VAS for pain and DLQI |
|
| NCT0368924 [170] |
Phase II placebo-controlled, double-blind study Guselkumab 200 mg at weeks 0, 4, 8 and 12 Guselkumab 1200 mg i.v. at weeks 0, 4 and 8, then 200 mg s.c. starting from week 12 Placebo |
50% achieved an HiSCR at week 16 45% achieved an HiSCR at week 16 38% achieved an HiSCR at week 16 |
|
| Risankizumab | |||
| Marques et al., 2021 [172]; Caposiena et al., 2021 [173]; Licata et al., 2021 [174] |
Case reports (n = 4) Risankizumab 150 mg s.c. at weeks 0 and 4, followed by 150 mg s.c. every 12 weeks |
Successful response to Risankizumab |
|
| Repetto et al., 2022 [175] |
Case series (n = 6) Risankizumab 150 mg s.c. at weeks 0 and 4, followed by 150 mg s.c. every 12 weeks |
50% achieved an HiSCR at month 3 and 100% achieved an HiSCR at month 6 |
|
| NCT03926169 [176] | Phase II placebo-controlled study | Still ongoing | |
| Tildrakizumab | |||
| Kok et al., 2020 [178]; Kok et al., 2021 [179] |
Case series (n = 9) Tildrakizumab 100 mg s.c. at weeks 0 and 4 and then 200 mg every 4 weeks |
100% achieved an HiSCR Reduction in mean AN count of 23.50 from baseline observed at month 15 |
|
| IL-1 | |||
| Anakinra | |||
| Tzanetakou et al., 2016 [193] |
Double-blind, randomized, placebo-controlled prospective clinical trial (n = 20) Anakinra 100 mg s.c. daily for 12 weeks (n = 10) Placebo s.c. (n = 10) |
78% achieved an HiSCR at week 12 30% achieved an HiSCR at week 12 After a 12-week observation period, the HiSCR difference between the groups was not significant |
|
| Leslie et al., 2014 [194] |
Open-label phase II study (n = 6) Anakinra 100 mg s.c. daily for 8 weeks |
Mean decrease of 34.8 points in modified Sartorius score. All patients experienced a rebound during an 8-week follow-up off-therapy period. |
|
| Zarchi et al., 2013 [195]; van der Zee et al., 2013 [105]; Russo et al., 2016 [196]; Menis et al., 2015 [197] |
Case reports (n= 5) Anakinra 100 mg s.c. daily |
1 successful response to anakinra 4 failures in response to anakinra |
|
| Bermekimab | |||
| Kanni et al., 2018 [199] |
Phase II placebo-controlled, double-blind RCT (NCT02643654) (n = 10) Bermekimab 7.5 mg/kg i.v. every other week Placebo i.v. |
60% achieved an HiSCR at week 12 10% achieved an HiSCR at week 12 |
|
| Kanni et al., 2021 [200] |
Open-label extension of NCT02643654 (n = 8) Bermekimab 7.5 mg/kg i.v. every other week |
75% achieved an HiSCR at week 12 |
|
| Gottlieb et al., 2020 [201] |
Phase II multicenter open label study (n = 42) Bermekimab 400 mg s.c. weekly |
61% of anti-TNF naïve patients achieved an HiSCR at week 12 63% of anti-TNF failure patients achieved an HiSCR at week 12 |
|
| NCT04988308 [202] | Phase IIa/IIb, multicenter, randomized, placebo- and active comparator-controlled, double-blind, dose-ranging study | Still ongoing | |
| Canakinumab | |||
| Houriet et al., 2017 [204]; Jaeger et al., 2013 [205]; Tekin et al., 2017 [206]; Sun et al., 2017 [207] |
Case reports (n = 6) Canakinumab 150 mg s.c. at day 1, then monthly Canakinumab 150 mg s.c. at day 1, day 15, then monthly Canakinumab 150 mg every week/4 weeks/8 week |
3 successful responses to canakinumab 3 failures in response to canakinumab |
|
| IL-36 | |||
| Spesolimab | |||
| NCT04762277 [218] | Phase II placebo-controlled, double-blind RCT | Still ongoing | |
| Imsidolimab (ANB019) | |||
| NCT04856930 [219] | Phase II placebo-controlled, double-blind RCT | Still ongoing | |