S Danese1, G Fiorino, W Reinisch. 1. IBD Unit, IBD Center, Division of Gastroenterology, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy.
Abstract
BACKGROUND: The addition of antitumour necrosis factor-α (TNF-α) agents to the therapeutic armamentarium against Crohn's disease has been a revolution in its management. However, approximately 25 to 40% of patients who initially benefit from anti-TNF-α treatment develop intolerable adverse events or lose their response during maintenance therapy. AIM: To summarise the current knowledge on the mechanisms underlying loss of response in these patients and the therapeutic strategies available to counteract this clinical challenge. METHOD: A literature search using PubMed, MedLine and Embase databases has been performed. RESULTS: Anti-infliximab antibodies formation and autoantibodies (ANA, anti-DNA and other autoantibodies) have been associated with loss of response. Individual differences in drug metabolism may contribute to loss of response. Smoking may be a risk factor for loss of response. Dose escalation, reduction of infusion intervals and switch to other anti-TNF-α agents are effective as rescue strategies. CONCLUSIONS: Loss of response appears to result from different causes not fully established by now. Optimization of therapies, or switch to other anti-TNF-α, are currently the best studied strategies in case of loss of response, and can be successful in 40-60% of patients who lose response.
BACKGROUND: The addition of antitumour necrosis factor-α (TNF-α) agents to the therapeutic armamentarium against Crohn's disease has been a revolution in its management. However, approximately 25 to 40% of patients who initially benefit from anti-TNF-α treatment develop intolerable adverse events or lose their response during maintenance therapy. AIM: To summarise the current knowledge on the mechanisms underlying loss of response in these patients and the therapeutic strategies available to counteract this clinical challenge. METHOD: A literature search using PubMed, MedLine and Embase databases has been performed. RESULTS: Anti-infliximab antibodies formation and autoantibodies (ANA, anti-DNA and other autoantibodies) have been associated with loss of response. Individual differences in drug metabolism may contribute to loss of response. Smoking may be a risk factor for loss of response. Dose escalation, reduction of infusion intervals and switch to other anti-TNF-α agents are effective as rescue strategies. CONCLUSIONS: Loss of response appears to result from different causes not fully established by now. Optimization of therapies, or switch to other anti-TNF-α, are currently the best studied strategies in case of loss of response, and can be successful in 40-60% of patients who lose response.
Authors: R Knobler; G Berlin; P Calzavara-Pinton; H Greinix; P Jaksch; L Laroche; J Ludvigsson; P Quaglino; W Reinisch; J Scarisbrick; T Schwarz; P Wolf; P Arenberger; C Assaf; M Bagot; M Barr; A Bohbot; L Bruckner-Tuderman; B Dreno; A Enk; L French; R Gniadecki; H Gollnick; M Hertl; C Jantschitsch; A Jung; U Just; C-D Klemke; U Lippert; T Luger; E Papadavid; H Pehamberger; A Ranki; R Stadler; W Sterry; I H Wolf; M Worm; J Zic; C C Zouboulis; U Hillen Journal: J Eur Acad Dermatol Venereol Date: 2014-01 Impact factor: 6.166