ECCO 2017. P151. Shorter time to cessation of rectal bleeding with combined oral and topical mesalazine (PENTASA®) for ulcerative colitis: Results from the PINCE trial
P. Marteau, S. Lindgren, P. Broberg, C.S.J. Probert
Results: Rectal bleeding ceased in 40/52 patients (76.9%) in the mesalazine enema group, and in 16/30 patients (53.3%) in the placebo enema group (eight patients in the active group and 13 in the placebo group did not have rectal bleeding at baseline). The mesalazine enema group had a significantly shorter time to cessation of rectal bleeding than the placebo enema group (p = 0.0025). Mean duration of rectal bleeding was 21.0 days with mesalazine enema and 24.4 days with placebo enema (Table 1). In 35.0% and 25.0% of patients, rectal bleeding ceased within 7 days of study start in the mesalazine and placebo enema groups, respectively; rectal bleeding ceased later than day 28 in 32.5% and 37.5%, respectively. In 50% of mesalazine enema patients, there was cessation of rectal bleeding at ~28 days (from Kaplan–Meier analysis), whereas this was achieved after >56 days in the placebo enema group. The time to the cessation of rectal bleeding in patients with frank blood at baseline was also shorter with mesalazine enema and in these patients, there was cessation of rectal bleeding in 50% of the mesalazine enema group at ~21 days, whereas it took >56 days in the placebo enema group.
Table 1. Time to cessation of rectal bleeding (days), ITT population
Conclusion: Cessation of rectal bleeding was achieved by significantly more patients with mesalazine enema than with placebo enema. In addition, the time taken to cease rectal bleeding was significantly shorter in patients receiving combination oral and enema mesalazine than oral mesalazine alone, demonstrating improved efficacy of combination treatment in reducing the symptoms of UC.
CARE Faculty Perspective: The PINCE trial considered the impact of mono oral mesalazine (PENTASA®) therapy versus combination (oral and enema) mesalazine therapy in patients with mild-to-moderate UC. Results found that combination therapy was more effective in relieving rectal bleeding symptoms rapidly.
A supplemental analysis from this trial looked specifically at the QoL of patients taking combination vs. monotherapy and found a measurable benefit (using the Euro-Quality of Life Scoring System) in terms of mobility, usual activity and anxiety/depression in patients receiving combination therapy (oral PENTASA® & enema) with active UC. (ECCO 2017. P261; C.S.J. Probert et al.)
ECCO 2017. DOP018. Effect of adalimumab on extraintestinal manifestations among patients with ulcerative colitis in a clinical practice setting: results from INSPIRADA
Travis S., Feagan B., Peyrin-Biroulet L., Panaccione R., Danese S., Lazar A., Robinson A., Thakkar R., Pappalardo B., Petersson J., Bereswill M., Chen N., Skup M.
Results: Data from 461 patients were analysed. At BL, 88 patients (19.1%) had an extraintestinal manifestations (EIMs). The most commonly reported EIM was arthritis (84 of 88 patients). Pyoderma gangrenosum, erythema nodosum, and uveitis each were reported in <1% of patients at BL and at Weeks 2, 8, and 26. The overall percentage of patients with any EIM decreased significantly (p<0.001) from BL over time: 13.2%, 11.7%, and 10.8% had any EIMs at Weeks 2, 8, and 26, respectively. Similar decreasing percentages were seen for patients with arthritis: 13.0%, 11.7%, and 10.8% at Weeks 2, 8, and 26, respectively.
Among those with any EIM at BL, resolution of EIMs increased
over time: 39.8%, 52.3%, and 63.6% at Weeks 2, 8, and 26, respectively; durable resolution was 23.9% and 44.3% at Weeks 2 and 8, respectively.
Among those with arthritis at BL, resolution rates were 36.9%, 50.0%, and 61.9% at Weeks 2, 8, and 26, respectively; durable resolution was 20.2%, 41.7%, and 61.9%, respectively.
Conclusion: ADA therapy reduced EIMs among patients with moderate to severe UC in usual clinical practice, with EIM resolution in 60% by Week 26.
CARE Faculty Perspective: Extraintestinal manifestations (EIMs), such as arthritis, pyoderma gangrenosum, erythema nodosum, uveitis, etc., are common in patients with UC and can significantly impact quality of life and morbidity.
The INSPIRADA trial aimed to analyse the effect of adalimumab on the resolution of EIMs. Results suggest that adalimumab significantly increased patients’ resolution of all EIMs from Week 2 to Week 26.
ECCO 2017. P468. Etrolizumab treatment improves histological activity as assessed by the Robarts histopathology index
Feagan B.G., De Hertogh G., Peyrin-Biroulet L., Rubin D.T., Maciuca R., McBride J., Arulmani U., Scherl A.
Results: Analysis included 89 (of 119 efficacy-evaluable) patients with BL histological data and BL RHI >1. Mean week 10 RHI reduction was greater for etrolizumab- compared with PBO-treated patients regardless of previous aTNF experience, and a greater proportion of patients receiving etrolizumab achieved histological improvement compared with PBO. Of patients with an endoscopic subscore (ES) ≤1 at week 10, 89% experienced histological improvement. Mean (SD) RHI change was −14.2 (5.5) in patients with an ES ≤1 at week 10 versus −2.5 (9.5) in patients with an ES >1.
Figure 4. Histologic Improvement
Conclusion: RHI-measured histological activity improved after 10 weeks of etrolizumab treatment. Consistent with the clinical remission rates observed in EUCALYPTUS, the magnitude of histological improvement was greater in the aTNF-naive vs
aTNF-IR subgroup. RHI reductions are associated with improved ES at week 10.
CARE Faculty Perspective: Etrolizumab is an anti-β7 monoclonal antibody targeting α4β7 and αEβ7 integrins, being investigated for moderate-to-severe UC patients. This trial assessed the effect etrolizumab has on histological inflammation in mucosal biopsies using the Robarts histopathology index (RHI). Histological improvement was better with etrolizumab versus placebo in both anti-TNF naïve and experienced populations, however it was better among the former.