Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?
Abstract
:1. Introduction
2. JAK–STAT Pathway
2.1. Mechanism of JAK-STAT Signaling Pathway
2.2. Inhibition of JAK-STAT Signaling Pathway
2.3. Main Inhibitors of JAK/STAT Pathway
2.3.1. Tofacitinib
2.3.2. Baricitinib
2.3.3. Other New Therapies under Study
Ruxolitinib
Solcitinib
R333
Brepocitinib
Filgotinib
Upadacitinib
Deucravacitinib
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Disease | Drug | Study ID/Ongoing Trials | Trial Phase Study Design | Number of Patients | Study Duration | Disease Activity Score | Dosage of JAK Inhibitor/day | Concomitant Immuno-Suppressive Agents |
---|---|---|---|---|---|---|---|---|
SLE | TOFACITINIB | Hasni et al., 2021 (NCT02535689) [35,36] | Phase Ib Double blind Controlled | 30 | 8 weeks + followed 4 weeks | SLEDAI 2K BILAG 2004 DAS28-ESR, PGA, SF-36, CLASI | 5 mg × 2 | NO |
SLE/CLE | TOFACITINIB | NCT03288324 [49] | Phase Ib/II Open label | 20 | 76 weeks | CLASI SLEDAI BILAG | 5 mg × 2 | YES |
SLE/DLE | TOFACITINIB | NCT03159936 [50] | Phase I/II | 5 | 6 months | CLASI | 5 mg × 2 | YES |
SLE | TOFACITINIB | You et al., 2019 [45] | Case series | 10 | 4 weeks to 12 months | SLEDAI | 5 mg × 2 | YES |
CLE | TOFACITINIB | Bonnardeaux et al., 2022 [46] | Case series | 3 | 1 to 7 months | CLASI | 5 mg × 2 | YES |
Disease Drug Study ID/Ongoing Trials | Primary Endpoints | Secondary Endpoints | Results |
---|---|---|---|
SLE TOFACITINIB Hasni et al., 2021 (NCT02535689) [35,36] |
|
|
|
SLE/CLE TOFACITINIB (NCT03288324) [49] |
|
| Estimated study completion date: June 2024. |
DLE TOFACITINIB (NCT03159936) [50] |
| - | Stopped due to an insufficient number of subjects. |
SLE TOFACITINIB You et al., 2019 [45] |
| - |
|
CLE TOFACITINIB Bonnardeaux et al., 2022 [46] |
|
|
|
Disease | Drug | Study ID/Ongoing Trials | Trial Phase Study Design | Number of Patients | Study Duration | Disease Activity Score | Dosage of JAK Inhibitor | Concomitant Immuno-Suppressive Agents |
---|---|---|---|---|---|---|---|---|
SLE/CLE | BARICITINIB | Wallace et al., 2018 [3] (NCT02708095) Study JAHH [54] | Phase 2 trial Double blind Controlled | 314 | 24 weeks | SLEDAI-2K | BARICITINIB 2 mg/day, or BARICITINIB 4 mg/day | YES |
SLE/CLE | BARICITINIB | BRAVE I (NCT03616912) Study JAHZ [67] | Phase III Double blind Controlled | 750 | 52 weeks | CLASI | BARICITINIB 2 mg/day, or BARICITINIB 4 mg/day | YES |
SLE/CLE | BARICITINIB | BRAVE II (NCT03616964) Study JAIA [68] | Phase III Double blind Controlled | 777 | 52 weeks | LLDAS CLASI | BARICITINIB 2 mg/day, or BARICITINIB 4 mg/day | YES |
SLE | BARICITINIB | SLE-BRAVE X (NCT03843125) [69] | Phase III Double blind | 1100 | 156 weeks | LLDAS CLASI | BARICITINIB 2 mg/day, or BARICITINIB 4 mg/day | YES |
CLE | BARICITINIB | Zimmermann et al., 2019 [64] | Case series | 3 | 3 months | R-CLASI VAS | BARICITINIB 4 mg/day | NO |
Disease Drug Study ID/Ongoing Trials | Primary Endpoints | Secondary Endpoints | Results |
---|---|---|---|
SLE/CLE BARICITINIB Wallace et al., 2018 [3] (NCT02708095) [54] |
|
|
|
SLE/CLE BARICITINIB BRAVE I (NCT03616912) [67] |
|
| Study completion: March 2022 -study was stopped due to the insufficient data to support a positive benefit risk ratio. |
SLE/CLE BARICITINIB BRAVE II (NCT03616964) [68] |
|
| Completed -no results yet published. |
SLE BARICITINIB SLE-BRAVE X (NCT03843125) [69] |
|
| Study completion: March 2022 -study terminated as there was no enough data to support a positive benefit risk ratio. |
CLE BARICITINIB Zimmermann et al., 2019 [64] |
| - |
|
Disease Drug Study ID/Ongoing trials | Number of Patients Study Duration Disease Activity Score | Dosage of JAK Inhibitor | Results |
---|---|---|---|
SLE SOLCITINIB Kahl et al., 2019 [75] (NCT01777256) [77] |
| Solcitinib 50/100/200/400 mg × 2/day vs. PBO |
|
SLE BREPOCITINIB (NCT03845517) [80] |
| Brepocitinib 15 mg/30 mg/45 mg vs. PBO | Estimated study completion date: August 2023; -no results yet published. |
SLE UPADACITINIB (NCT03978520) SLEek [83] |
| Upadacitinib dose A or dose B vs. PBO vs. Elsubrutinib | Estimated completion date: July 2022; -no results yet published. |
SLE/DLE R333 (NCT01597050) [79] |
| R333 6% (60 mg/g) × 2/day | Presto et al. concluded that R333 treatment did not show a significant improvement in dermal modifications [78]. |
CLE FILGOTINIB (NCT03134222) [81] |
| Filgotinib 200 mg/day vs. Lanraplenib 30 mg /day PBO | Completed -primary endpoint (CLASI activity score) not met [87]. |
LMN FILGOTINIB (NCT03285711) [82] |
| Filgotinib 200 mg/day vs. Lanraplenib 30 mg/day | Completed -limited results due to the small number of patients [88]. |
SLE DEUCRAVACITINIB (NCT03252587) [85] |
| Deucravacitinib dose 1 or dose 2 or dose 3 vs PBO | Completed -no results yet published. |
SLE DEUCRAVACITINIB (NCT03920267) [86] |
| Deucravacitinib dose 1 or dose 2 or dose 3 | Estimated study completion date: November 2023. |
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Richter, P.; Cardoneanu, A.; Burlui, A.M.; Macovei, L.A.; Bratoiu, I.; Buliga-Finis, O.N.; Rezus, E. Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus? Int. J. Mol. Sci. 2022, 23, 11788. https://doi.org/10.3390/ijms231911788
Richter P, Cardoneanu A, Burlui AM, Macovei LA, Bratoiu I, Buliga-Finis ON, Rezus E. Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus? International Journal of Molecular Sciences. 2022; 23(19):11788. https://doi.org/10.3390/ijms231911788
Chicago/Turabian StyleRichter, Patricia, Anca Cardoneanu, Alexandra Maria Burlui, Luana Andreea Macovei, Ioana Bratoiu, Oana Nicoleta Buliga-Finis, and Elena Rezus. 2022. "Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?" International Journal of Molecular Sciences 23, no. 19: 11788. https://doi.org/10.3390/ijms231911788