Highlights from

European Crohn’s and Colitis Organisation

Congress 2018

Vienna 14-17 February 2018

Combining new drugs with different mechanisms

As IBD is a mechanically complex disease characterised by a high heterogeneity, it is highly unlikely that one treatment will be sufficient.

Combinations of drugs can lead to a numerically greater efficacy (albeit with more serious adverse events (AEs)), for example when etanercept (anti-TNF agonist) and abatacept (CTLA-4-agonist) have been combined [1]. The same is true when an anti-TNF (etanercept/adalimumab) is combined with anti-CD20 (rituximab) [2]. However, the combination of etanercept and anakinra (IL-1 receptor antagonist) showed no greater efficacy, whilst there were no serious infections with etanercept [3].

The EXPLORER study aims to determine the effect of triple combination therapy on endoscopic remission in participants. It combines an anti-integrin (vedolizumab IV), TNF antagonist (adalimumab SC), and IMM (oral methotrexate). Newly-diagnosed CD patients are stratified at higher risk for complications [4]. Moreover, there are various approaches to develop bi-specific antibody drugs (also called dual-variable domain antibodies) [5].

In methotrexate-treated RA patients in remission, a dual-variable domain immunoglobulin (Ig) which simultaneously targets human TNF and IL-17A is currently being evaluated [6]. Although combinations of biologics may offer better efficacy than monotherapy, there are some caveats. For example, the recognition of possible opposing pathways or cell subsets, potentially increased side effects and increased costs.

Combining new drugs with different mechanisms of action may seem tempting, but more data are needed. Different combinations of agents are already used in daily practice or may become available shortly [7].

  1. Weinblatt M, et al. Ann Rheum Dis. 2007;66:228-34.
  2. Greenwald MW, et al. Arthritis Rheum. 2011;63(3):622-32.
  3. Genovese MC, et al. Arthritis Rheum. 2004;50(5):1412-9.
  4. www.clinicaltrials.gov; NCT02764762.
  5. Yu S, et al. J Hematol Oncol. 2017;10(1):155.
  6. Fleischmann RM, et al. Arthritis Rheum. 2017;69:2283-91.
  7. Ben-Horin S, et al. ECCO 2018.

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