Third-line rescue treatment avoids colectomy in over half of patients with acute severe ulcerative colitis non responsive to corticosteroids and second-line treatment, making it a potentially effective therapeutic option, a study suggests.

But researchers say the risks are not negligible with one-third of patients experiencing at least one adverse event including death, making the therapy best suited for a select group of patients in specialist centres.

Published in Alimentary Pharmacology and Therapeutics [link here], their retrospective study included 78 patients from Spain with acute severe ulcerative colitis (ASUC) refractory to intravenous steroids who did not respond to infliximab (41%) or ciclosporin (59%) as second-line rescue treatment.

The patients received third-line therapy in the same hospitalisation: infliximab (58%), ciclosporin (22%), tofacitinib (17%) and ustekinumab (3.8%).

When it came to patient characteristics, a high proportion had severe anaemia (42%) and/or severe hypoalbuminaemia (65%), while 82% had documented severe endoscopic disease activity before third-line treatment.

Two patients developed toxic megacolon during hospitalisation.

During a median 21-weeks of follow-up, colectomy was performed in 29 patients, of which 86% occurred within the first month of third-line therapy.

Reasons for colectomy included primary non-response to third-line rescue treatment in 23 patients (79%), partial response (10%), loss of response (6.9%), and colonic perforation after hospital discharge (6.9%).

Colectomy risk factors included older age at hospital admission, ciclosporin as third-line salvage therapy and severe disease measured by partial Mayo score before the third-line therapy, multivariable analysis showed.

One third of patients treated with infliximab as third-line therapy underwent colectomy, while for ciclosporin, ustekinumab and tofacitinib, the proportion of patients undergoing colectomy were 53%, 33% and 31%, respectively.

Findings showed a clinical response to third-line rescue treatment seven days after initiation in 72% of patients. The median time of hospitalisation after initiation was also a week for patients who did not require colectomy.

Thirty-two patients achieved clinical remission at 12 weeks and 18 at 52 weeks.

At last study visit, some 25 patients were still being treated with a third-line rescue drug, while 12 had ceased during follow-up due to clinical remission.

Overall, 53 patients discontinued third-line treatment, almost half within the first 12 weeks. This was due to persistence of inflammatory activity (62%), clinical remission (23%) and adverse events (15%), noted the researchers.

Meanwhile, adverse events were reported in a third of patients, most of whom experienced resolution of the events without any sequela. Infections such as urinary and cytomegalovirus (15%) and infusion reactions (6.4%) were the most frequently reported adverse events, the researchers said.

Serious adverse events were observed in 14 patients.

Two patients exposed to ciclosporin as a third-line therapy died, including one following colectomy. Both patients were young with no associated comorbidities, underscoring the necessity of risk and benefit discussions in a multidisciplinary team, the researchers said.

“Our study reveals that a third-line avoids colectomy in more than half of the patients at week 52… Furthermore, the most frequent cause of colectomy was primary non-response; therefore, the likelihood of colectomy eight weeks after admission for ASUC was very low in our study,” they said.

“This result suggests that third-line rescue treatment might represent a promising bridging strategy in ASUC and therefore, other biologics or JAK inhibitors might be considered for UC management in the outpatient setting as well.”

The researchers concluded that close monitoring post rescue therapy and timely decision-making between continuing medical treatment or colectomy was essential for assessing response and minimising morbidity and mortality.

Some authors received financial support from pharmaceutical companies.