Comparative efficacy of antitumor necrosis factor agents and tacrolimus in naïve steroid-refractory ulcerative colitis patients

Abstract

While retrospective studies have compared the efficacy of anti-tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short-and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent-and TAC-naïve steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients. Ulcerative colitis (UC) is a disabling chronic inflammatory condition of the large intestine of unknown aetiology. Moreover, UC markedly impairs patients' quality of life due to its symptoms such as diarrhoea, bloody stool, abdominal cramps, and faecal urgency 1,2. Conventional therapeutic options including 5-aminosalicylates as first-line therapy and corticosteroids as second-line therapy, are effective in inducing remission in the majority of UC patients. However, 20-50% of patients are either resistant to or dependent on steroids 3-5. Additionally, a subset of the patients is not able to tolerate steroid therapy due to side effects such as worsening of diabetes, osteoporosis, and high blood pressure.

The efficacy and safety of infliximab and calcineurin inhibitors in steroid-refractory UC patients: A meta-analysis

“…After reading the titles and abstracts and reviewing the full texts, 19 publications including 1,323 steroid-refractory UC patients were included in the meta-analysis. [ 9 10 27 ] There were 616 patients treated with IFX, 536 patients treated with CYS, and 171 patients treated with TAC. The clinical characteristics of the included studies are listed in Table 1 .…”

Oral Tacrolimus in Steroid Refractory and Dependent Pediatric Ulcerative Colitis—A Systematic Review and Meta-Analysis

“…In patients who are refractory to steroids, the options available for induction of remission are either anti-TNF drugs or CNIs. Both these agents have similar short-term efficacy in steroid refractory colitis (17). Anti-TNF therapy is expensive and in a resource poor setting a combination of tacrolimus (for induction) and thiopurines (for maintenance) may be preferred over anti-TNF therapy in thiopurine naïve patients.…”

Efficacy and Safety of Infliximab Versus Adalimumab in Adult Subjects With Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis

“…Subjects with inflammatory bowel diseases (UC and CD) or UC only who were prescribed IFX and ADA and were biologic-naïve were the study population. The included studies' sample sizes ranged from 25 [ 20 ] to 3340 [ 22 ], with a total population of 8,070. Of them, 3,035 (37.6%) patients were treated with ADA, and 5,035 (62.4%) were treated with IFX.…”

“…The baseline characteristics were generally comparable in the two arms. However, the IFX-treated patients had a significantly more severe disease in the studies of Ma et al [ 16 ], Lee et al [ 26 ], Dalal et al [ 29 ], and Cassinotti et al [ 27 ], longer follow-up period in the study of Singh et al [ 18 ], higher use of steroids and other immunomodulators in the study of Chen et al [ 22 ], shorter disease duration in the studies of Han et al [ 24 ] and Cassinotti et al [ 27 ], longer previous use of steroids and other immunomodulators in the work of Han et al [ 24 ], lower use of steroids and other immunomodulators in the study of Dalal et al [ 29 ], and different ethnic groups (lower in White and higher in Black/African) in the study of Sandborn et al [ 17 ].…”

“…The included studies' sample sizes ranged from 25 [20] to 3340 [22], with a total population of 8,070. Of them, 3,035 (37.6%) patients were treated with ADA, and 5,035 (62.4%) were treated with IFX.…”