Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa
Abstract
:1. Introduction
2. Pathogenesis
3. Current Biologics
4. TNF-α Inhibitors
4.1. Adalimumab
4.2. Infliximab
4.3. Etanercept
4.4. Golimumab
4.5. Certolizumab
5. IL-17 Inhibitors
5.1. Secukinumab
5.2. Ixekizumab
5.3. Bimekizumab
5.4. Brodalumab
5.5. CMJ112
6. IL-23 Inhibitors
6.1. Ustekinumab
6.2. Guselkumab
6.3. Risankizumab
7. IL-1 Inhibitors
7.1. Anakinra
7.2. Bermekimab
8. IL-36 Inhibitors
9. Other Biologic Agents
10. JAK Inhibitors
11. Conclusions and Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug | Study | Study Details | Study Results |
---|---|---|---|
TNF-α inhibitors | |||
Adalimumab | Kimball et al., 2016 [67] | PIONEER I (n = 307) Adalimumab 40 mg weekly SC (n = 153) | 41.8% achieved HiSCR at week 12 |
Placebo (n = 154) | 26.0% achieved HiSCR at week 12 | ||
PIONEER II (n = 326) Adalimumab 40 mg weekly SC (n = 163) | 58.9% achieved HiSCR at week 12 | ||
Placebo (n = 163) | 27.6% achieved HiSCR at week 12 | ||
Zouboulis et al., 2019 [68] | Open-label extension (OLE) (n = 151) Adalimumab 40 mg weekly | 52.3% met HiSCR at week 168 | |
Infliximab | Grant et al., 2010 [69] | Phase II RCT (n = 38) Infliximab 5 mg/kg IV at weeks 0, 2, 4, 6, 14, and 22 (n = 15) | 27% met ≥50% reduction in HSSI |
Placebo (n = 18) | 5% met ≥50% reduction in HSSI | ||
Ghias et al., 2020 [70] | Prospective open-label study (n = 42) Infliximab 7.5 mg/kg every 4 weeks | 47.6% achieved clinical response at week 4 and 70.8% at week 12 | |
Infliximab 10 mg/kg every 4 weeks | 37.5% achieved clinical response at week 4 and 50% at week 12 | ||
Etanercept | Lee et al., 2009 [71] | Phase II open-label trial (n = 15) Etanercept 50 mg weekly | 29% reported moderate improvement at 12 weeks |
Adams et al., 2010 [72] | Randomized, double-blind trial (n = 20) Etanercept 50 mg twice weekly (n = 10) Placebo (n = 10) | No significant difference in PGA, patient global assessment, or DLQI between etanercept and placebo groups at 12 or 24 weeks | |
Golimumab | Ramos et al., 2022 [73] | Case report (n = 2) | Successful response to golimumab |
Melendez-Gonzalez et al., 2021 [74] | Retrospective cohort study (n = 13) Golimumab 2 mg/kg or 200 mg every 4 weeks | 6/9 patients with available data for HiSCR calculation achieved HiSCR. IHS4 significantly improved, but other assessments did not show significant improvement | |
Certolizumab | Esme et al., 2022 [75] | Retrospective cohort study (n = 11) Certilizumab 400 mg every 2 weeks | 54.5% achieved HiSCR at week 12 with significant decreases in DLQI and IHS4 at weeks 12 and 24 |
IL-17 inhibitors | |||
Secukinumab | Prussick et al., 2019 [76] | Open-label trial (n = 9) Secukinumab 300 mg weekly for 5 weeks then every 4 weeks | 67% achieved HiSCR at 24 weeks |
Casseres et al., 2020 [77] | Open-label trial (n = 20) Secukinumab 300 mg weekly for 5 weeks then every 2 weeks (n = 11) or every 4 weeks (n = 9) | 70% achieved HiSCR by week 24, including 5/6 patients with prior exposure to TNF-α inhibitors | |
Kimball et al., 2023 [78] | SUNSHINE trial (n = 541) Secukinumab 300 mg every 2 weeks (n = 141) | 45% met HiSCR at 16 weeks | |
Secukinumab every 4 weeks (n = 180) | 42% met HiSCR at 16 weeks | ||
Placebo (n = 180) | 34% met HiSCR at 16 weeks Secukinumab every 4 weeks vs. placebo not statistically significant. Responses were sustained through week 52 | ||
SUNRISE trial (n = 543) Secukinumab 300 mg every 2 weeks (n = 180) | 42% met HiSCR at 16 weeks | ||
Secukinumab every 4 weeks (n = 180) | 46% met HiSCR at 16 weeks | ||
Placebo (n = 183) | 31% met HiSCR at 16 weeks Both comparator group results were significantly higher than placebo. Responses were sustained through week 52. | ||
Ixekizumab | Odorici et al., 2020 [79,80] Megna et al., 2020 [79,80] | Case reports (n = 2) | Successful response to ixekizumab |
Esme et al., 2022 [81]. | Case series (n = 5) Ixekizumab 160 mg once, then 80 mg every two weeks through week 12 | 4/5 patients achieved HiSCR | |
Bimekizumab | Glatt et al., 2021 [82] | Phase II RCT (n = 90) Bimekizumab 640 mg at week 0 then 320 mg every 2 weeks (n = 46) | 57% achieved HiSCR at week 12 |
Placebo (n = 21) | 26% achieved HiSCR at week 12 | ||
Adalimumab 160 mg at week 0, 80 mg at week 2, then 40 mg every week (n = 21) | 60% achieved HiSCR at week 12 | ||
NCT04242446, NCT04242498, NCT04901195 [83] | Phase III RCTs | Ongoing | |
Brodalumab | Yoshida et al., 2021 [84,85] Vagnozzi et al., 2023 [84,85] | Case reports (n = 2) | Successful response to brodalumab |
Frew et al., 2020 [86] | Open-label cohort study (n = 10) Brodalumab 210 mg at weeks 0, 1, and 2, then 210 mg every 2 weeks | 100% achieved HiSCR at week 12 | |
Frew et al., 2021 [86,87] | Open-label cohort study (n = 10) Brodalumab 210 mg weekly | 100% achieved HiSCR at week 4 | |
CMJ112 | Kimball et al., 2022 [88]. | Phase II RCT CMJ112 300 mg weekly for first five doses, then every 2 weeks until week 16 (n = 33) | 32.3% HS-PGA responders at week 16 |
Placebo (n = 33) | 12.5% HS-PGA responders at week 16 | ||
Izokibep | NCT05905783 [83] | Phase III RCT | Ongoing |
Sonelokimab | NCT05322473 [83] | Phase II RCT | Ongoing |
IL-23 inhibitors | |||
Ustekinumab | Hollywood et al., 2022 [89,90] Valenzuela-Ubiña et al., 2022 [89,90]. | Retrospective cohort study (n = 16) and case series (n = 10) | Successful response to ustekinumab |
Blok et al., 2016 [91] | Open-label cohort study (n = 17) Ustekinumab 45 mg or 90 mg (psoriasis dosing regimen; patients >100 kg received 90 mg) | 35% experienced ≥ 50% reduction in mSS and 47% achieved HiSCR at week 40. | |
Scholl et al., 2019 [92] | Case series Ustekinumab 90 mg every 8 to 12 weeks | Successful response to high-dose ustekinumab | |
Jiang et al., 2022 [93] | Ustekinumab 90 mg every 4 weeks | ||
Guselkumab | Kearney et al., 2020 [94,95,96] Berman et al., 2021 [94,95,96] Casseres et al., 2019 [94,95,96] | Case reports (n = 2) and retrospective cohort study (n = 8) | Successful response to guselkumab |
Dudink et al., 2023 [97] | Phase II open-label study (n = 20) Guselkumab 200 mg every 4 weeks | 65% achieved HiSCR at 16 weeks | |
Kimball et al., 2023 [98] | Phase II RCT (n = 184) Guselkumab 200 mg SC every 4 weeks (n = 59) | 50.8% achieved HiSCR at week 16 | |
Guselkumab 1200 mg IV every 4 weeks for 12 weeks then 200 mg SC every 4 weeks (n = 60) | 45.0% achieved HiSCR at week 16 | ||
Placebo (n = 62) | 38.7% achieved HiSCR at week 16 Results of treatment groups to placebo were not statistically significant. | ||
Risankizumab | Repetto et al., 2022 [99] | Case series (n = 6) Risankizumab 150 mg at week 0 and 4, then every 12 weeks thereafter (psoriasis dosing) | 3/6 achieved HiSCR at month 3, and all achieved HiSCR at month 6 |
Kimball et al., 2023 [100] | Phase II RCT (n = 243) Risankizumab 180 mg at weeks 0, 1, 2, 4, and 12 (n = 80) | 46.8% achieved HiSCR at week 16 | |
Risankizumab 360 mg at weeks 0, 1, 2, 4, and 12 (n = 81) | 43.4% achieved HiSCR at week 16 | ||
Placebo (n = 82) | 41.5% achieved HiSCR at week 16 The study was prematurely terminated due to poor efficacy results. | ||
IL-1 inhibitors | |||
Anakinra | Zarchi et al., 2013 [101,102] | Case report (n = 1) | Successful response to anakinra |
Russo and Alikhan, 2016 [101,102] | Case report (n = 1) | Unsuccessful response to anakinra | |
Tzanetakou et al., 2016 [103] | Phase II RCT (n = 20) Anakinra 100 mg daily (n = 10) | 78% achieved HiSCR at 12 weeks | |
Placebo (n = 10) | 30% achieved HiSCR at 12 weeks | ||
Leslie et al., 2014 [104] | Case series (n = 6) Anakinra 100 mg daily | Successful response to anakinra | |
Bermekimab (MABp1) | Kanni et al., 2018 [105] | Phase II RCT (n = 20) Bermekimab 7.5 mg/kg IV every 2 weeks (n = 10) | 60% achieved HiSCR at week 12 |
Placebo (n = 10) | 10% achieved HiSCR at week 12 | ||
Kanni et al., 2021 [106] | Phase II OLE (n = 8) | 75% achieved HiSCR at week 12 | |
Gottlieb et al., 2020 [107] | Phase II open-label study (n = 42) Bermekimab 400 mg weekly (n = 24) (participants who previously failed anti-TNF therapy) | 63% achieved HiSCR at 12 weeks | |
Bermekimab 400 mg weekly (n = 18) (anti-TNF naïve participants) | 61% achieved HiSCR at 12 weeks | ||
NCT04988308 [83] | Phase II RCT (n = 151) | Prematurely terminated due to meeting futility criteria | |
Lutikizumab | NCT05139602 [83] | Phase II RCT | Ongoing |
IL-36 inhibitors | |||
Spesolimab | NCT04762277 [83] | Phase II RCT | Ongoing |
Imsidolimab | NCT04856930 [83] | Phase II RCT | Ongoing |
CXCR1/2 inhibitors | |||
Eltrekibart | NCT06046729 [83] | Phase II RCT | Ongoing |
TNF-OX40L inhibitors | |||
SAR442970 | NCT05849922 [83] | Phase II RCT | Ongoing |
JAK inhibitors | |||
INCB054707 (povorcitinib) | Alavi et al., 2022 [108] | Study 1: open-label RCT (n = 10) INCB054707 15 mg once daily | 43% achieved HiSCR at week 8 |
Study 2: phase II RCT INCB054707 30 mg once daily (n = 9) | 56% achieved HiSCR at week 8 | ||
INCB054707 60 mg once daily (n = 9) | 56% achieved HiSCR at week 8 | ||
INCB054707 90 mg once daily (n = 8) | 88% achieved HiSCR at week 8 | ||
Placebo (n = 9) | 57% achieved HiSCR at week 8 | ||
Upadacitinib | Kozera et al., 2022 [109] | Retrospective cohort study (n = 20) Upadacitinib 15 mg daily for 4 weeks. Dose increased to 30 mg daily if clinical response was not sufficient after 4 weeks | 75% achieved HiSCR at week 4 and 100% achieved HiSCR at week 12 |
NCT04430855 [83] | Phase II RCT | Results not yet published | |
NCT05889182 [83] | Phase III RCT | Ongoing |
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Chen, R.; Guo, R.; Petty, A.J.; Jaleel, T. Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa. Immuno 2024, 4, 57-76. https://doi.org/10.3390/immuno4010004
Chen R, Guo R, Petty AJ, Jaleel T. Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa. Immuno. 2024; 4(1):57-76. https://doi.org/10.3390/immuno4010004
Chicago/Turabian StyleChen, Rene, Robyn Guo, Amy J. Petty, and Tarannum Jaleel. 2024. "Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa" Immuno 4, no. 1: 57-76. https://doi.org/10.3390/immuno4010004