# Real-World Comparative Efficacy and Safety of Upadacitinib, Tofacitinib, and Filgotinib in Patients With Ulcerative Colitis

**Authors:** Fraz Ahmad, Tausif Hussain, Chamith H Gunaratne, Joseph Collum, Abdul Ghaffar, Khaled Gharbia

PMC · DOI: 10.7759/cureus.102069 · 2026-01-22

## TL;DR

This study compares the effectiveness and safety of three JAK inhibitors in treating ulcerative colitis, finding upadacitinib to have the strongest response.

## Contribution

A real-world comparative analysis of three JAK inhibitors in UC patients, highlighting upadacitinib's superior biochemical response.

## Key findings

- Upadacitinib showed the highest rate of biochemical response (86.4%) compared to tofacitinib (62.5%) and filgotinib (50%).
- All three JAK inhibitors improved inflammatory biomarkers, with minimal serious side effects observed.
- Endoscopic improvements were most notable in upadacitinib and tofacitinib groups.

## Abstract

Janus kinase (JAK) inhibitors, including upadacitinib, tofacitinib, and filgotinib, represent an emerging class of effective oral therapies for the treatment of moderate to severe ulcerative colitis (UC). We report a real-world retrospective study evaluating the comparative efficacy and safety of these three JAK inhibitors in 52 patients ranging from mild to severe UC. Significant improvements in inflammatory biomarkers were observed across all treatment groups, with biochemical response (reduction in faecal calprotectin (FCP)) achieved in 21/22 upadacitinib-treated patients, 22/24 tofacitinib-treated patients, and 5/6 filgotinib-treated patients. High-grade biochemical response (≥75% FCP reduction or normalization) was most frequently observed with upadacitinib (86.4%; N=19), followed by tofacitinib (62.5%; N=15) and filgotinib (50%; N=3). Endoscopic reassessment was available in a subset of patients, and the majority showed improvement or resolution of endoscopic inflammation, particularly in the upadacitinib and tofacitinib groups. The safety profile was consistent with recognized JAK inhibitor side effects, with hyperlipidemia being the most common adverse event and intermittent cytopenias noted in some patients; no serious opportunistic infections or thromboembolic events were recorded. These findings suggest that all three JAK inhibitors are effective therapeutic options in real-world practice, with upadacitinib demonstrating the strongest overall biochemical response among this treatment-experienced UC cohort. Larger prospective studies are warranted to confirm the long-term efficacy of these agents.

## Linked entities

- **Chemicals:** upadacitinib (PubChem CID 58557659), tofacitinib (PubChem CID 9926791), filgotinib (PubChem CID 49831257)
- **Diseases:** ulcerative colitis (MONDO:0005101), hyperlipidemia (MONDO:0021187)

## Full-text entities

- **Genes:** FCP1 (F-cell production 1) [NCBI Gene 2221] {aka FCP, FCPX, HBFQTL3}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}
- **Diseases:** metabolic abnormality (MESH:D008659), Hyperlipidemia (MESH:D006949), Leucopenia (MESH:C536227), colonic mucosal inflammation (MESH:D007249), dyslipidemia (MESH:D050171), opportunistic infections (MESH:D009894), hypercholesterolemia (MESH:D006937), Chronic idiopathic inflammatory bowel disease (MESH:D015212), thromboembolic (MESH:D013923), inflammatory intestinal damage (MESH:D007410), herpes zoster (MESH:D006562), UC (MESH:D003093), thrombotic (MESH:D013927), cytopenias (MESH:D006402), VTE (MESH:D054556), thrombocytopenia (MESH:D013921), indeterminate colitis (MESH:D003092), Crohn's disease (MESH:D003424)
- **Chemicals:** methotrexate (MESH:D008727), adalimumab (MESH:D000068879), infliximab (MESH:D000069285), ustekinumab (MESH:D000069549), Upadacitinib (MESH:C000613732), Tofacitinib (MESH:C479163), azathioprine (MESH:D001379), steroid (MESH:D013256), lipid (MESH:D008055), Filgotinib (MESH:C584571), Janus (-), hydroxychloroquine (MESH:D006886), 6-mercaptopurine (MESH:D015122), vedolizumab (MESH:C543529)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12925624/full.md

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Source: https://tomesphere.com/paper/PMC12925624