Insights into the Pathogenesis of HS and Therapeutical Approaches
Abstract
:1. Introduction
2. Insights into the Pathogenesis of HS
2.1. How Much Does Genetics Play a Role in HS?
2.2. Lifestyle
2.2.1. Obesity
2.2.2. Tobacco Smoking
2.3. The Role of Cutaneous Microbiome in HS
2.4. Sex Hormones
2.5. The Histopathological Findings
2.6. Innate Immunity
2.7. HS Cytokine Milieu
2.7.1. IL-1 Cytokine Family
2.7.2. TNF-α and IFNs
2.7.3. IL-17 Cytokine Family
2.7.4. IL-12 Cytokine Family
2.7.5. IL-10 Cytokine Family
2.7.6. IL-6
2.8. An Overview of the Pathogenetic Mechanisms in HS
3. (New Medical) Therapeutical Approaches in HS
3.1. TNF-α Inhibitors
3.1.1. Adalimumab
3.1.2. Infliximab
3.1.3. Etanercept
3.1.4. Golimumab
3.1.5. Certolizumab Pegol
3.2. IL-1 Inhibitors
3.2.1. Anakinra
3.2.2. Canakinumab
3.2.3. Bermekimab
3.3. IL-17 Inhibitors
3.3.1. Secukinumab
3.3.2. Ixekizumab
3.3.3. Brodalumab
3.3.4. Bimekizumab
3.3.5. CJM112
3.4. IL-12/-23 Inhibitors
Ustekinumab
3.5. IL-23 Inhibitors
3.5.1. Guselkumab
3.5.2. Risankizumab
3.5.3. Tildrakizumab
3.6. Complement 5a Inhibitors
FX-1
3.7. Phosphodiesterase 4 (PDE4) Inhibitors
Apremilast
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Intervention | Target | Primary Outcome | NCT Number | Phase | Status |
---|---|---|---|---|---|
CFZ533 (MA) LYS006 (SM) Placebo | CD40 LTA4H | HiSCR at 16 weeks | NCT03827798 [155] | Phase 2 | Recruiting |
Risankizumab (MA) Placebo | IL-23 | HiSCR at 16 weeks | NCT03926169 [156] | Phase 2 | Active, not recruiting |
Brodalumab (MA) | IL-17RA | IL-17RA saturation at week 12 | NCT04979520 [157] | Early Phase 1 | Recruiting |
Bimekizumab (MA) Placebo | IL-17A IL-17F | HiSCR at 16 weeks | NCT04242446 [158] | Phase 3 | Recruiting |
Bimekizumab (MA) Placebo | IL-17A IL-17F | HiSCR at 16 weeks | NCT04242498 [159] | Phase 3 | Recruiting |
Bimekizumab (MA) | IL-17A IL-17F | Percentage of participants with TEAEs up to week 120 | NCT04901195 [160] | Phase 3 | Enrolling by invitation |
Upadacitinib (SM) Placebo | JAK1/2 | HiSCR at 12 weeks | NCT04430855 [161] | Phase 2 | Active, not recruiting |
INCB054707 (SM) Placebo | JAK1 | Mean change in total AN count at 16 weeks | NCT04476043 [162] | Phase 2 | Recruiting |
Orismilast (SM) | PDE4 | Percent change in AN count at 16 weeks | NCT04982432 [163] | Phase 2 | Not yet recruiting |
Secukinumab (MA) | IL-17A | Time to LOR in HiSCR responders at weeks 52–104 | NCT04179175 [164] | Phase 3 | Recruiting |
Secukinumab (MA) Placebo | IL-17A | HiSCR at 16 weeks | NCT03713619 [165] | Phase 3 | Active, not recruiting |
Secukinumab (MA) Placebo | IL-17A | HiSCR at 16 weeks | NCT03713632 [166] | Phase 3 | Active, not recruiting |
Spesolimab (MA) Placebo | IL-36R | Percent change in total AN count at 12 weeks | NCT04762277 [167] | Phase 2 | Recruiting |
Spesolimab (MA) | IL-36R | Occurrence TEAEs up to week 120 | NCT04876391 [168] | Phase 2 | Not yet recruiting |
Imsidolimab (MA) Placebo solution | IL-36R | Change in AN count at 16 weeks | NCT04856930 [169] | Phase 2 | Not yet recruiting |
LY3041658 (MA) Placebo | ELR+CXC chemokine family | HiSCR at 16 weeks | NCT04493502 [170] | Phase 2 | Recruiting |
PF-06650833 (SM) PF-06700841 (SM) PF-06826647 (SM) Placebo | IRAK4 JAK1 TYK2 TYK2 | HiSCR at 16 weeks | NCT04092452 [171] | Phase 2 | Recruiting |
KT-474 (SM) | IRAK4 | Incidence and severity of TEAEs up to 28 days | NCT04772885 [172] | Phase 1 | Recruiting |
Guselkumab | IL-23 | Changes in levels of cytokines in the skin at week 0 and week 16 | NCT04061395 [173] | Phase 2 | Not yet recruiting |
Avacopan (SM) Placebo | C5aR | HiSCR at 12 weeks | NCT03852472 [174] | Phase 2 | Active, not recruiting |
Recombinant anti G-CSF receptor (MA) | G-CSF receptor | Incidence of TEAEs (up to 24 weeks) Incidence of AESIs | NCT03972280 [175] | Phase 1 | Recruiting |
Adalimumab (MA) Monotherapy Adalimumab + surgery | TNF-α | Cost-utility, 2 years | NCT03221621 [176] | Phase 4 | Recruiting |
Tofacitinib (SM) | JAK1 JAK3 | Number of SAEs up to week 18 Change in IFN scores (Baseline and 16 weeks) | NCT04246372 [177] | Phase 2 | Recruiting |
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Rosi, E.; Fastame, M.T.; Scandagli, I.; Di Cesare, A.; Ricceri, F.; Pimpinelli, N.; Prignano, F. Insights into the Pathogenesis of HS and Therapeutical Approaches. Biomedicines 2021, 9, 1168. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091168
Rosi E, Fastame MT, Scandagli I, Di Cesare A, Ricceri F, Pimpinelli N, Prignano F. Insights into the Pathogenesis of HS and Therapeutical Approaches. Biomedicines. 2021; 9(9):1168. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091168
Chicago/Turabian StyleRosi, Elia, Maria Thais Fastame, Ilaria Scandagli, Antonella Di Cesare, Federica Ricceri, Nicola Pimpinelli, and Francesca Prignano. 2021. "Insights into the Pathogenesis of HS and Therapeutical Approaches" Biomedicines 9, no. 9: 1168. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9091168