Abstract and Introduction
Abstract
Background One-third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti-TNFs do not respond to treatment, and a relevant proportion experience loss of response or intolerance.
Aim To investigate the efficacy and safety of a second anti-TNF agent after primary/secondary failure or intolerance to a first drug.
Methods Inclusion criteria: studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab-pegol (CZP) as the second anti-TNF in CD or UC. Search strategy: Bibliographical searches (PubMed/Embase). Data synthesis: percentage of response/remission; the meta-analysis was performed using the inverse variance method.
Results We included 46 studies (37 CD, 8 UC, 1 pouchitis). The CD studies comprised 32 switching IFX→ADA, 4 IFX→CZP and 1 ADA→IFX. Overall, the second anti-TNF after the failure of IFX in CD induced remission in 43% and response in 63% of patients. The remission rate was higher when the reason to withdraw the first anti-TNF was intolerance (61%) than after secondary (45%) or primary failure (30%); response rates were, respectively, 72%, 62% and 53%. All UC studies switched IFX→ADA, six of them reporting remission rates ranging from 0% to 50%. Adverse events rate ranged from 0% to 81% in CD, most of them mild (serious adverse event 0–21%, discontinuation rate <20%).
Conclusions The efficacy of a second anti-TNF in CD patients largely depends on the cause for switching. The remission rate is higher when the reason to withdraw the first anti-TNF is intolerance (61%), compared with secondary (45%) or primary failure (30%). Further studies of switch ADA→IFX are needed to evaluate this strategy. PROSPERO-registry-number: CRD42014012943.
Introduction
The use of drugs targeting tumour necrosis factor-α (anti-TNF) has greatly advanced the therapeutic armamentarium for the treatment of inflammatory bowel diseases (IBDs). Infliximab (IFX), followed by adalimumab (ADA) and certolizumab-pegol (CZP), have shown significant efficacy in Crohn's disease (CD) and ulcerative colitis (CU) refractory to conventional treatments, including immunosuppressive drugs. This clinical efficacy is associated with mucosal healing and improvement in quality of life. The efficacy of anti-TNF agents also exerts a major impact on the outcome of key disease parameters, such as fewer hospitalisations and surgical procedures.
However, approximately ⅓ of the IBD patients receiving anti-TNF agents do not respond to treatment (primary failure), and a significant proportion (>⅓) experience a loss of response (secondary failure) or intolerance to treatment. These scenarios pose a therapeutic challenge to gastroenterologists.
In routine clinical practice, a second anti-TNF drug is used when a first one has failed (irrespective of whether the patient is a primary nonresponder, secondary nonresponder, or intolerant). However, the true efficacy of this switch strategy has not been properly evaluated. The aim of the present study was to systematically review and perform a meta-analysis on the efficacy and safety of an anti-TNF treatment after a previous anti-TNF has failed, and to evaluate the different factors that can affect this response.