Ulcerative colitis

A multi-centred retrospective cohort study comparing JAK inhibitor therapies in moderate to severe ulcerative colitis (2025)

Posted on by

Type of publication:

Conference abstract

Author(s):

Kumar A.; Baxter J.; Rimmer P.; Noble B.; Makki M.; Chikhlia A.; Cheesbrough J.; Disney B.; *Muir J.; Karova M.; *Butterworth J.; Bower J.; Sagar N.; Al-Talib I.; Nahal J.; Hatta A.; Ali N.; Sagar V.; Varyani F.; Smith S.; Bourne S.; Hsu Y.K.; Eltahir A.; De silva S.; Harvey P.;

Citation:

Journal of Crohn's and Colitis. Conference: 20th Congress of ECCO. Berlin Germany. 19(Supplement 1) (pp i2143), 2025. Date of Publication: 01 Jan 2025.

Abstract:

Background: Tofacitinib, filgotinib and upadacitinib are JAK inhibitors (JAKi) that are licensed for treatment in moderate to severe ulcerative colitis (UC). Whilst these drugs have demonstrated efficacy against placebo, there is no head-to-head data. This study aims to compare the clinical efficacy between these drugs.

Method(s): This is a multi-centred, retrospective cohort study with data collected from January 2018 to June 2024. Patients with UC were recruited on their first JAKi, irrespective of previous advanced therapies. Clinical remission (faecal calprotectin (FCP) <250, Mayo 1, UCEIS 1, pMayo 2, SCCAI 2) and response (50% reduction in FCP from baseline, reduction in partial Mayo or UCEIS by 3 or more, or sustained <3) was measured at 3- and 6-months. If a patient stopped taking JAKi, they were considered to have failed both response and remission. Data was non-parametric and outcome measures were compared using Chi-squared tests.

Result(s): There was a total of 266 patients included in the final analysis. 70 (26%) were on upadacitinib, 47 (18%) on filgotinib and 149 (56%) on tofacitinib (Table 1). At least 87% (129/149) on tofacitinib had exposure to a previous biologic compared to 80% (56/70) for upadacitinib and 66% (31/47) for filgotinib. At 3-months, clinical response in upadacitinib, filgotinib and tofacitinib was demonstrated in 83%, 74% and 75% patients, respectively and clinical remission was seen in 69%, 64% and 52%, respectively. At 6-months, clinical response was demonstrated in 79%, 65% and 63%, respectively and remission was seen in 75%, 61% and 51%, respectively. Upadacitinib demonstrated significantly higher 3-months remission rate (p=0.019) and 6-months response (p=0.010) and remission rates (p= 0.001) compared to tofacitinib. In the bio-exposed cohorts, upadacitinib demonstrated greater 6-months remission rates (71%) compared to 64% on filgotinib (p=NS) and 52% tofacitinib (p= 0.022). In bio-naive cohorts (n=50), upadacitinib demonstrated greater 6-months remission rates (93%) compared to 56% on filgotinib (p=0.024) and 50% tofacitinib (p= 0.009). Combining the JAKi, 90% of patients were not on steroids at 3-months and 94% were not on steroids at 6-months. A total of 26 patients had a colectomy at the time of their JAKi, 17 on tofacitinib, 5 on filgotinib and 4 on upadacitinib.

Conclusion(s): This study demonstrates that upadacitinib is more likely to achieve 3- and 6-month remission compared to tofacitinib. In a small subgroup of bio-naive patients Upadacitinib was more likely to achieve 6-month remission compared to filgotinib and tofacitinib. JAKi were associated with minimal adverse events and importantly, the efficacy of JAKi does not appear diminished by prior biologic use.

Link to full-text [no password required]

A Complex Case of Adalimumab Induced Pleuropericarditis in a Patient with Underlying Ulcerative Colitis (2021)

Posted on by

Type of publication:
Journal article

Author(s):
*Abbasi A, *Day S, Subahani M, *Townson G

Citation:
Asploro Journal of Biomedical and Clinical Case Reports, 2021 Jan; 4(1) p.16-21

Abstract:
Introduction: Adalimumab is an anti-tumour necrosis factor (anti-TNF) monoclonal antibody and an important part of the treatment regime for autoimmune conditions including inflammatory bowel disease. We present a case of adalimumab induced pleuropericarditis and discuss the diagnosis challenges we faced.
Case History: A 22-year-old male presented to the emergency department with 3 days history of headache, malaise, fever and right-sided chest pain. He was diagnosed with ulcerative colitis 8 months ago but failed to respond to mesalazine, requiring high dose steroids to induce disease remission. His mesalazine was stopped after 4 months and he was initiated on adalimumab 2 months prior to the current presentation. At presentation, he had a temperature of 38.7 °C (101.6 °F) but no other physical signs. His inflammatory markers were raised, and the chest x-ray was clear. He was started on empirical intravenous antibiotics on suspicion of the underlying infective process. On day 4 the patient developed a new pleural rub and crepitations on both lung bases. An urgent echocardiogram and computed tomography scan of the thorax abdomen and pelvis revealed pleural effusion and a 1.8 cm diameter pericardial effusion. Extensive investigation including virology screen, autoimmune screen and pleural fluid analysis were normal.
Diagnosis, Management and Outcome: This case was discussed in a multidisciplinary meeting. A diagnosis of pleuropericarditis secondary to adalimumab was made. Adalimumab and antibiotics were stopped, and he was started on a course of oral steroids. The patient responded well to the treatment and his symptoms resolved.
Conclusion: Rare drug toxicity should be part of differential diagnosis, especially in young patients with unusual presentation. An early multidisciplinary approach is crucial for a positive outcome. The patient should be actively involved in decision making to improve long term outcome.

Link to full-text [no password required]

A randomised, multi-centre, double-blind, placebo-controlled study of a targeted release oral cyclosporine formulation in the treatment of mild-to-moderate ulcerative colitis: Efficacy results (2019)

Posted on by

Type of publication:
Conference abstract

Author(s):
Bloom S.; Iqbal T.; Nwokolo C.; *Smith M.; O'Donoghue D.; Hall J.; Dzyngel B.

Citation:
Journal of Crohn's and Colitis; Mar 2019; vol. 13

Abstract:
Background: Cyclosporine (CsA) is an effective treatment for patients with acute severe ulcerative colitis (UC), and studies have shown that it has an impact on disease activity comparable to the anti-TNF agent,
infliximab.1,2 Concerns regarding systemic toxicities have limited its role to short-term induction therapy and as a bridge to other therapies. ST-0529 is a novel low dose, controlled release formulation of CsA. A Phase 1 dose-ranging study demonstrated that tissue concentrations improved when it is given twice daily (BID).3
Methods: A total of 118 subjects with mild (baseline DAI < 6) or moderate (baseline DAI >= 6) UC were
randomised 1:1 to receive 75 mg ST-0529 once daily or placebo (53 and 65 patients, respectively) for 4 weeks in a multi-centre, randomised, double-blind, placebo-controlled, Phase IIa study. Patients using UC medications (eg low-dose steroids, 5-aminosalicylates, and immunomodulatory agents) on screening could continue them if agreed to maintain a stable dosing regimen during the study. The primary objective was to evaluate the efficacy of ST-0529 in inducing clinical remission (DAI score <=2, with no individual score >1 and rectal bleeding subscore of 0 or 1). The secondary objectives included clinical response, mucosal and histological healing, safety, and tolerability.
Result(s): A numerical although not statistically significant advantage of ST-0529 over placebo was found for rates of clinical remission (ST-0529: 13.2%; placebo: 6.3%, p = 0.2211) and clinical response (ST-0529: 30.2%; placebo: 18.8%, p = 0.1923). There were no differences between the treatment groups for mucosal and histological healing. ST-0529 was safe and well-tolerated. A post hoc subgroup analysis was performed to evaluate effects by disease severity. Clinical remission and clinical response rates in subjects with moderate (baseline DAI >=6) and mild (baseline DAI <6) disease (ITT, N = 118)
Conclusion(s): In this pilot study, ST-0529 given once daily, was safe, well tolerated, and showed a numerically higher, but not statistically significant difference in remission rate in patients with mild-to-moderate UC compared with placebo after 4 weeks of treatment. In the post hoc analysis, differences in the clinical response between treatment subgroups achieved statistical significance in some subgroups, the largest clinical response rate in moderate UC patients taking 5-aminosalicylates and/or steroids. These preliminary data, added to the data from a Phase 1 study, support further development of ST-0529 as a treatment for the induction and maintenance of remission in UC patients with moderate to severe disease. (Table Presented).

Link to full-text [NHS OpenAthens account required]