Background In recent years the use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered daily practice.In vitro studies they have shown a different selectivity ^[1], which however has not yet been confirmed in real life studies. Furthermore, considering recent developments, an in-depth study regarding the global safety of these drugs is needed.

Objectives To address potential differences in the safety of Janus kinase inhibitors and short-term efficacy on disease activity we characterized their safety profile in RA patient population.

Methods Single center retrospective observational study. The sample consisted of 68 patients receiving any of the following JAK-is: Tofacitinib, Upadacitinib, Filgotinib, Baricitinib, with a mean of 19.3 months of therapy and a diagnosis of RA according to the ACR/EULAR 2010 criteria. We collected and recorded the clinical features; any infections or adverse reactions during therapy; clinimetry at time 0 and at 6 months. For the statistical analysis, the χ2 (chi-square) test was used to evaluate whether there were statistical differences with respect to categorical variables, Anova one-way to evaluate any statistical difference with respect to continuous variables; mixed effects model and paired t-test for clinimetry comparison.

Results We found no statistically significant differences between JAK-Is in the following outcomes: symptomatic Covid, p=0.388, new malignancies p=0.348, cardiovascular events p=0.788, thrombocytosis p=0.681, neutropenia p=0.962, lymphopenia p=0.935, anemia p=0.227, need to use glucocorticoids p=0.13, need to use Dmards p= 0.217, permanent discontinuation of therapy = 0.353. In our sample we had only development of 2 cardiovascular events, 1 DVT and a new diagnosis of cancer. Anova one-way showed no difference in the number zoster episodes (p=0.587), or other serious infections (p=0.193). The paired t-test showed that there was a class effect on the reduction of activity indices already after 6 months of therapy (DAS 28 pcr p=0.017, SDAI p=0.054, CDAI p=0.021). However, the mixed effects model showed that there was no molecule more effective in reducing disease activity considering the outcomes at 6 months (DAS 28 pcr p=0.445, SDAI p=0.639, CDAI p=0.467).

Conclusion The originality of our study was to compare the four different molecules in a real-life study. We prove that JAK inhibition is effective in a real-world population of RA patients. The lack of diversity between JAK-Is in efficacy outcomes, adverse reactions and infections could be explained by considering that their selectivity has only been demonstrated in vitro-studies. Meta-analyses performed on clinical trials confirmed lack of diversity in outcomes ^[2]. Furthermore, JAK is known to dimerize when activated in biological systems, but the percentage of different dimers is unknown. Therefore, further comparative studies are needed to verify their selectivity in real-life studies.

References

1. Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis. 2021 Jul;80(7):865-875. doi: 10.1136/annrheumdis-2020-219012. Epub 2021 Mar 19. PMID: 33741556; PMCID: PMC8237188.
2. Ho Lee Y, Gyu Song G. Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for active rheumatoid arthritis. J Clin Pharm Ther. 2020 Aug;45(4):674-681. doi: 10.1111/jcpt.13142. Epub 2020 Jun 3. PMID: 32495356.

Acknowledgements: NIL.

Disclosure of Interests None Declared.

Keywords: Rheumatoid arthritis, Targeted synthetic drugs, Safety

DOI: 10.1136/annrheumdis-2023-eular.467