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 |
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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