Tofacitinib and Baricitinib in Type 2 Diabetic Patients with Rheumatoid Arthritis
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Traves, P.G.; Murray, B.; Campigotto, F.; Galien, R.; Meng, A.; Di Paolo, J.A. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann. Rheum. Dis. 2021, 80, 865–875. [Google Scholar] [CrossRef] [PubMed]
- Smolen, J.S.; Landewé, R.B.M.; Bergstra, S.A.; Kerschbaumer, A.; Sepriano, A.; Aletaha, D.; Caporali, R.; Edwards, C.J.; Hyrich, K.L.; E Pope, J.; et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann. Rheum. Dis. 2023, 82, 3–18. [Google Scholar] [CrossRef] [PubMed]
- Dodington, D.W.; Desai, H.R.; Woo, M. JAK/STAT—Emerging Players in Metabolism. Trends Endocrinol. Metab. 2018, 29, 55–65. [Google Scholar] [CrossRef] [PubMed]
- Thirone, A.C.; JeBailey, L.; Bilan, P.J.; Klip, A. Opposite effect of JAK2 on insulin-dependent activation of mitogen-activated protein kinases and Akt in muscle cells: Possible target to ameliorate insulin resistance. Diabetes 2006, 55, 942–951. [Google Scholar] [CrossRef] [PubMed]
- Collotta, D.; Franchina, M.P.; Carlucci, V.; Collino, M. Recent advances in JAK inhibitors for the treatment of metabolic syndrome. Front. Pharmacol. 2023, 14, 1245535. [Google Scholar] [CrossRef] [PubMed]
- Waibel, M.; Wentworth, J.M.; So, M.; Couper, J.J.; Cameron, F.J.; MacIsaac, R.J.; Atlas, G.; Gorelik, A.; Litwak, S.; Sanz-Villanueva, L.; et al. Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes. N. Engl. J. Med. 2023, 389, 2140–2150. [Google Scholar] [CrossRef] [PubMed]
- Gurzov, E.N.; Stanley, W.J.; Pappas, E.G.; Thomas, H.E.; Gough, D.J. The JAK/STAT pathway in obesity and diabetes. FEBS J. 2016, 283, 3002–3015. [Google Scholar] [CrossRef] [PubMed]
- European Medicines Agency—EMA. Tofacitinib: EPAR—Product Information. 2023. Available online: https://www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf (accessed on 20 December 2023).
- European Medicines Agency—EMA. Baricitinib: EPAR—Product Information. 2023. Available online: https://www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_en.pdf (accessed on 20 December 2023).
- Aletaha, D.; Neogi, T.; Silman, A.J.; Funovits, J.; Felson, D.T.; Bingham, C.O., 3rd; Birnbaum, N.S.; Burmester, G.R.; Bykerk, V.P.; Cohen, M.D.; et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann. Rheum. Dis. 2010, 69, 1580–1588. [Google Scholar] [CrossRef] [PubMed]
- England, B.R.; Tiong, B.K.; Bergman, M.J.; Curtis, J.R.; Kazi, S.; Mikuls, T.R.; O’Dell, J.R.; Ranganath, V.K.; Limanni, A.; Suter, L.G.; et al. 2019 Update of the American College of Rheumatology Recommended Rheumatoid Arthritis Disease Activity Measures. Arthritis Care Res. 2019, 71, 1540–1555. [Google Scholar] [CrossRef] [PubMed]
- Van Lint, J.A.; van Hunsel, F.P.A.M.; Tas, S.W.; Vonkeman, H.E.; Hoentjen, F.; A van Doorn, M.B.; Hebing, R.C.F.; Nurmohamed, M.T.; Bemt, B.J.F.v.D.; van Puijenbroek, E.P.; et al. Hypoglycaemia following JAK inhibitor treatment in patients with diabetes. Ann. Rheum. Dis. 2022, 81, 597–599. [Google Scholar] [CrossRef] [PubMed]
- Collotta, D.; Hull, W.; Mastrocola, R.; Chiazza, F.; Cento, A.S.; Murphy, C.; Verta, R.; Alves, G.F.; Gaudioso, G.; Fava, F.; et al. Baricitinib counteracts metaflammation, thus protecting against diet-induced metabolic abnormalities in mice. Mol. Metab. 2020, 39, 101009. [Google Scholar] [CrossRef] [PubMed]
- Bako, H.Y.; Ibrahim, M.A.; Isah, M.S.; Ibrahim, S. Inhibition of JAK-STAT and NF-κB signalling systems could be a novel therapeutic target against insulin resistance and type 2 diabetes. Life Sci. 2019, 239, 117045. [Google Scholar] [CrossRef] [PubMed]
- Bates, S.H.; Stearns, W.H.; Dundon, T.A.; Schubert, M.; Tso, A.W.K.; Wang, Y.; Banks, A.S.; Lavery, H.J.; Haq, A.K.; Maratos-Flier, E.; et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 2003, 421, 856–859. [Google Scholar] [CrossRef] [PubMed]
Parameters | TOFA (n = 6; 46.2%) | BARI (n = 7; 53.8%) | p-Value |
---|---|---|---|
Age (years), median [IQR] | 74 [62–80] | 71 [58–73] | 0.566 |
Sex (female), n (%) | 5 (83.3) | 4 (57.1) | 0.559 |
RA disease activity score | |||
DAS28-ESR, median [IQR] | 4.8 [3.6–5.1] | 5.1 [4.3–5.1] | 0.721 |
DAS28-CRP, median [IQR] | 4.6 [4.2–4.6] | 4.2 [3.6–4.5] | 0.391 |
CDAI, median [IQR] | 21.5 [15.0–23.0] | 16.0 [15.0–22.0] | 0.614 |
SDAI, median [IQR] | 21.2 [16.2–26.2] | 16.4 [14.1–25.8] | 0.668 |
Previous bDMARDs | |||
Adalimumab, n (%) | 2 (33.3) | 1 (14.29) | 0.559 |
Certolizumab, n (%) | 3 (50.0) | 2 (28.6) | 0.573 |
Etanercept, n (%) | 4 (66.7) | 3 (42.9) | 0.592 |
Golimumab, n (%) | 1 (16.7) | 0 (0.0) | 0.462 |
Infliximab, n (%) | 6 (100) | 7 (100) | - |
Tocilizumab, n (%) | 4 (66.7) | 3 (42.9) | 0.592 |
Sarilumab, n (%) | 0 (0.0) | 2 (28.6) | 0.453 |
Abatacept, n (%) | 2 (33.3) | 1 (14.29) | 0.559 |
Rituximab, n (%) | 0 (0.0) | 1 (14.29) | 1.000 |
RA treatment | |||
GC, n (%) | 4 (66.7) | 4 (57.1) | 1.000 |
PDN dose equivalent (mg/day), median [IQR] | 5.0 [0.0–5.0] | 5.0 [0.0–5.0] | 0.735 |
csDMARD | |||
MTX, n (%) | 2 (33.3) | 2 (28.6) | 1.000 |
MTX dose (mg/week), median [IQR] | 0.0 [0.0–5.0] | 0.0 [0.0–5.0] | 0.859 |
Other csDMARD, n (%) | 0 (0.0) | 0 (0.0) | - |
T2DM monitoring | |||
HbA1c (%), median [IQR] | 7.1 [6.1–8.2] | 7.6 [6.5–7.9] | 0.774 |
T2DM treatment | |||
OAD use, n (%) | 5 (83.3) | 5 (71.4) | 1.000 |
OAD use + insulin use, n (%) | 1 (16.7) | 2 (28.6) | 1.000 |
BMI (kg/m2), median [IQR] | 26.9 [22.6–32.2] | 28.7 [26.8–34.0] | 0.520 |
Parameters | TOFA-1 | TOFA-2 | TOFA-3 | TOFA-4 | TOFA-5 | TOFA-6 | p-Value |
---|---|---|---|---|---|---|---|
Sex | F | F | F | F | M | F | |
Age (years) | 80 | 53 | 62 | 71 | 77 | 82 | |
HbA1c (%) | |||||||
Prior to TOFA | 6.2 | 9.7 | 6.1 | 8.2 | 7.9 | 5.7 | 0.416 |
At 6 months | 6.2 | 8.6 | 6.2 | 8.1 | 6.4 | 5.8 | |
AD dosage | NA | NA | NA | NA | NA | NA | |
Prior to TOFA | M850/24 | M1/12 + S50/12 | M850/12 | M850/24 + E10/24 + IAI | M850/12 + S50/12 | M850/12 | |
At 6 months | M850/24 | M1/12 + S50/12 | M850/12 | M850/24 + E10/24 + IAI | M850/12 + S50/12 | M850/12 | |
BMI (kg/m2) | |||||||
Prior to TOFA | 24.0 | 29.7 | 32.2 | 34.0 | 20.7 | 25.6 | 0.159 |
At 6 months | 24.0 | 30.4 | 32.2 | 34.0 | 21.9 | 25.6 | |
RA disease activity | |||||||
Prior to TOFA | MDA | MDA | MDA | MDA | HDA | HDA | - |
DAS28-ESR | 3.61 | 4.52 | 5.05 | 3.55 | 5.10 | 5.51 | |
DAS28-CRP | 4.17 | 4.60 | 4.53 | 3.03 | 4.62 | 4.62 | |
CDAI | 22.00 | 21.00 | 15.00 | 11.00 | 33.00 | 23.00 | |
SDAI | 16.20 | 25.10 | 17.30 | 12.10 | 38.60 | 26.20 | |
At 6 months | Rem | LDA | Rem | Rem | LDA | LDA | |
DAS28-ESR | 1.19 | 3.15 | 2.49 | 1.81 | 3.17 | 2.90 | |
DAS28-CRP | 1.75 | 2.75 | 1.17 | 1.52 | 2.28 | 2.16 | |
CDAI | 2.00 | 10.00 | 1.00 | 2.00 | 8.00 | 8.00 | |
SDAI | 3.10 | 10.20 | 0.80 | 3.30 | 10.60 | 10.50 | |
RA treatment | |||||||
GC (mg/day) | |||||||
Prior to TOFA | 0.0 | 0.0 | 5.0 | 5.0 | 5.0 | 5.0 | 0.157 |
At 6 months | 0.0 | 0.0 | 2.5 | 2.5 | 5.0 | 5.0 | |
MTX (mg/week) | |||||||
Prior to TOFA | 5.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 | - |
At 6 months | 5.0 | 0.0 | 5.0 | 0.0 | 0.0 | 0.0 |
Parameters | BARI-1 | BARI-2 | BARI-3 | BARI-4 | BARI-5 | BARI-6 | BARI-7 | p-Value |
---|---|---|---|---|---|---|---|---|
Sex | F | F | M | M | F | M | F | |
Age (years) | 58 | 54 | 71 | 73 | 80 | 63 | 73 | |
HbA1c (%) | ||||||||
Prior to BARI | 8.2 | 7.6 | 7.4 | 6.5 | 6.4 | 7.6 | 7.9 | 0.035 |
At 6 months | 6.8 | 6.5 | 6.6 | 6.4 | 6.0 | 7.6 | 6.8 | |
AD dosage | NA | DD | NA | NA | DD | NA | NA | |
Prior to BARI | M850/12 | M850/12 | P15/24 + IAI | M1/24 + P30/24 + LAI | M850/12 | M850/24 | M850/24 | |
At 6 months | M850/12 | M850/24 | P15/24 + IAI | M1/24 + P30/24 + LAI | M850/24 | M850/24 | M850/24 | |
BMI (kg/m2) | ||||||||
Prior to BARI | 28.4 | 30.7 | 35.6 | 28.7 | 22.2 | 26.8 | 34.0 | 0.022 |
At 6 months | 28.7 | 33.0 | 36.4 | 30.0 | 22.6 | 27.2 | 34.0 | |
RA disease activity | ||||||||
Prior to BARI | MDA | HDA | MDA | MDA | MDA | MDA | MDA | - |
DAS28-ESR | 5.08 | 6.44 | 5.06 | 4.31 | 3.93 | 4.50 | 5.05 | |
DAS28-CRP | 4.48 | 7.14 | 4.39 | 3.14 | 4.07 | 3.59 | 4.23 | |
CDAI | 22.00 | 54.00 | 15.00 | 14.00 | 16.00 | 16.00 | 15.00 | |
SDAI | 25.80 | 55.00 | 15.90 | 14.10 | 18.40 | 16.40 | 12.80 | |
At 6 months | Rem | LDA | Rem | LDA | LDA | LDA | LDA | |
DAS28-ESR | 2.28 | 3.17 | 0.28 | 3.05 | 2.96 | 3.10 | 3.06 | |
DAS28-CRP | 2.28 | 2.29 | 1.89 | 2.44 | 2.63 | 2.49 | 2.59 | |
CDAI | 2.00 | 10.00 | 2.00 | 7.00 | 8.00 | 8.00 | 5.00 | |
SDAI | 2.70 | 10.50 | 2.50 | 7.20 | 8.70 | 8.20 | 6.20 | |
RA treatment | ||||||||
GC (mg/day) | ||||||||
Prior to BARI | 0.0 | 0.0 | 5.0 | 0.0 | 5.0 | 5.0 | 5.0 | 0.317 |
At 6 months | 0.0 | 0.0 | 5.0 | 0.0 | 2.5 | 5.0 | 5.0 | |
MTX (mg/week) | ||||||||
Prior to BARI | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 | - |
At 6 months | 5.0 | 0.0 | 0.0 | 0.0 | 0.0 | 5.0 | 0.0 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Martinez-Molina, C.; Diaz-Torne, C.; Park, H.S.; Feliu, A.; Vidal, S.; Corominas, H. Tofacitinib and Baricitinib in Type 2 Diabetic Patients with Rheumatoid Arthritis. Medicina 2024, 60, 360. https://doi.org/10.3390/medicina60030360
Martinez-Molina C, Diaz-Torne C, Park HS, Feliu A, Vidal S, Corominas H. Tofacitinib and Baricitinib in Type 2 Diabetic Patients with Rheumatoid Arthritis. Medicina. 2024; 60(3):360. https://doi.org/10.3390/medicina60030360
Chicago/Turabian StyleMartinez-Molina, Cristina, Cesar Diaz-Torne, Hye S. Park, Anna Feliu, Silvia Vidal, and Hèctor Corominas. 2024. "Tofacitinib and Baricitinib in Type 2 Diabetic Patients with Rheumatoid Arthritis" Medicina 60, no. 3: 360. https://doi.org/10.3390/medicina60030360
APA StyleMartinez-Molina, C., Diaz-Torne, C., Park, H. S., Feliu, A., Vidal, S., & Corominas, H. (2024). Tofacitinib and Baricitinib in Type 2 Diabetic Patients with Rheumatoid Arthritis. Medicina, 60(3), 360. https://doi.org/10.3390/medicina60030360