Commentary: larazotide acetate ‐ an exciting new development for coeliac patients? Authors’ reply

a reduction in lactulose-to-mannitol (LAMA) ratio compared with controls. LAMA is a surrogate marker of intestinal permeability, and therefore effectiveness of treatment. The data presented shows no significant difference between treatment and control arms. This was also the case in the only other previously reported larazotide acetate study. Do we therefore use a reduction in symptoms as a measure of effectiveness, as has been demonstrated in the larazotide acetate 1 mg cohort? Although anti-tissue transglutaminase (tTG) antibodies were demonstrated to be lower in the treatment arms, compared with controls, there was still an increase compared with baseline, suggesting some gluten reaction even if symptoms were reduced. This raises the question of long-term safety, and the risk of coeliac disease-related complications. Histological assessment of treatment success may also be difficult with intraepithelial lymphocytosis still present in 40% of patients, despite adherence to GFD. Kelly et al. have chosen a group of patients in whom there was apparent good control of their coeliac disease with negative anti-tTG antibodies. Is it justifiable to offer a treatment to patients whose disease is controlled with a simple nontoxic dietary measure? Would it be more appropriate to use this drug in patients who find it difficult to adhere to a GFD? Would patients who are unable to adhere to a GFD find it any easier to take regular medications? Previous suggestions for a ‘gluten holiday’ may suit medications of this nature more easily. However, the average diet contains 13 g of gluten per day, whereas the gluten challenge in this study was only 2.7 g, equivalent to 1 slice of bread per day. This may not satisfy a patient’s desire to eat a normal diet. Nevertheless, patients do not find GFD a satisfactory treatment and are open to the possibility of novel therapies. The investigators should be commended for pursuing this novel option and demonstrating that larazotide acetate is a well-tolerated potential treatment, with good short-term safety. Perhaps the next step is targeting patients who are not adherent to a GFD and assessing the effect of larazotide acetate in this cohort.