Efficacy and Safety of Maintenance Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension

Abstract

Background and Aims The UNIFI long-term extension (LTE) study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through three years of maintenance therapy. Methods Patients randomized to ustekinumab q12w or q8w at maintenance baseline (N=348) and randomized ustekinumab-treated patients in the LTE (N=284) were evaluated. Symptomatic remission (Mayo stool frequency=0/1, rectal bleeding=0) was assessed. Safety included all LTE patients (N=188 placebo and N=457 ustekinumab). Results Among patients randomized to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at week 152. Overall, 20% of patients discontinued ustekinumab, 10% of biologicnaïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at year 3, 94.6% and 98.0% of patients were also corticosteroid free. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at week 152. Remission rates were higher for biologic-naïve patients than those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased CRP and fecal calprotectin measurements over 3 years. From weeks 96-156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma (BCC) reported 2 BCC. One patient in the q8w ustekinumab group who was receiving concomitant 6-mercaptopurine experienced SAEs of neutropenic sepsis and oral herpes. Conclusion Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.

Novedades en colitis ulcerosa: a propósito de la aprobación en México de un nuevo mecanismo de acción anti-interleucinas 12 y 23 (ustekinumab)

“…Las alternativas de tratamiento para la CU se han ampliado cada vez más últimamente, derivado de una mejor comprensión de la patogenia y la identificación de citocinas clave que promueven la inflamación intestinal 1,3,5,12,13,15,16 . Las IL 12 y 23 son dos citocinas clave en la patogenia de la inflamación intestinal.…”

“…El ustekinumab es un anticuerpo monoclonal humanizado IgG1 Kappa dirigido contra la subunidad P40 común para las IL 12 y 23 10 . Se aprobó por primera vez en 2019 como tratamiento para la CU moderada a grave tras el estudio UNIFI, que demostró su eficacia y seguridad 9,[12][13][14][15] . Y posteriormente el estudio UNIFI LTE demostró la persistencia de la eficacia a largo plazo, así como su adecuado perfil de seguridad en el seguimiento hasta 156 semanas y la baja Figura 6.…”

“…Hasta la semana 156 de la extensión a largo plazo, el 5.5% de los pacientes que recibieron ustekinumab dieron positivo para la formación de anticuerpos y del total solo un 22.7% para anticuerpos neutralizantes. El estudio concluye que la eficacia de ustekinumab en los pacientes con CU se confirmó a lo largo de los tres años sin nuevas señas de seguridad 13 .…”

“…A: población general. B: subgrupos de antecedente de tratamiento biológico (tomada de Abreu et al, 2022 13 ).…”

Targeting IL12/23 in ulcerative colitis: update on the role of ustekinumab

“…At week 152, 54.1% and 56.3% of patients were in symptomatic remission in the ustekinumab q12w and q8w groups, respectively ( p = ns). 48 …”