Abhinav Vasudevan

Time to clinical response and remission for therapeutics in inflammatory bowel diseases: What should the clinician expect, what should patients be told?

An awareness of the expected time for therapies to induce symptomatic improvement and remission is necessary for determining the timing of follow-up, disease (re)assessment, and the duration to persist with therapies, yet this is seldom reported as an outcome in clinical trials. In this review, we explore the time to clinical response and remission of current therapies for inflammatory bowel disease (IBD) as well as medication, patient and disease related factors that may influence the time to clinical response. It appears that the time to therapeutic response varies depending on the indication for therapy (Crohn’s disease or ulcerative colitis). Agents with the most rapid time to clinical response included corticosteroids, calcineurin inhibitors, exclusive enteral nutrition, aminosalicylates and anti-tumor necrosis factor therapy which will work in most patients within the first 2 mo. Vedolizumab, methotrexate and thiopurines had a longer time to clinical response and can take several months to achieve maximal efficacy. Factors affecting the time to clinical response of therapies included use of concomitant therapy, disease duration, smoking status, disease phenotype and advanced age. There appears to be marked variation in time to clinical response for therapies used in IBD which is further influenced by disease and patient related factors. Understanding the expected time to therapeutic response is integral to inform further decision making, maintain a patient-centered approach and ensure treatment is given an appropriate timeframe to achieve maximal benefit prior to cessation.

Low-dose thiopurine with allopurinol co-therapy overcomes thiopurine intolerance and allows thiopurine continuation in inflammatory bowel disease

AIMS To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. METHODS A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. RESULTS Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance. 64/89 (72%) had Crohns disease, 38 (43%) were males, median age at switch was 40y (range 17-78), median IBD duration 6y (0-29). Median follow-up was 1.9y (0-5). Reasons for switching to co-therapy included fatigue (37%), hepatotoxicity (23%), nausea (23%), arthralgia (10%), headache (12%) and hypersensitivity reaction (4%). Overall, 66 (74%) patients remained on co-therapy until most recent review and achieved a clinical response. High rates of overcoming intolerance (62-100%) occurred with co-therapy for all reasons above, although fatigue was less amenable to switching than non-fatigue indications (62% vs 91%, p = <0.001). Of 34 patients not escalated to biologics with endoscopic data, 15 were in remission (44%) at most recent review. CONCLUSION Low-dose thiopurine combined with allopurinol appears safe and effective in overcoming intolerances to thiopurine monotherapy in many cases.

Letter: overcoming secondary loss of response to infliximab-it is not the drug, it is how you use it!

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A rare presentation of Beals syndrome; a newly recognized connective tissue disorder

Beals syndrome is an autosomal-dominant connective tissue disorder, similar in many respects to Marfan syndrome, characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae, and muscular hypoplasia. This relatively new syndrome contrasted with Marfan by much less incidences of eye and heart anomalies and the congenital presence of contractures. It was found by Beals and Hecht in 1972 when they identified 2 cases of Beals syndrome; it was also thought that the original case described by Marfan in 1896 was actually a case of contractural arachnodactyly rather than a case of Marfan syndrome. Beals syndrome has distinct features, however, and is caused by a mutation in the fibrillin-2 gene (FBN2) in 5q23; Marfan syndrome is caused by mutations in fibrillin-1. We present a case of a patient with Beals syndrome who presented to the emergency department with a history of fractures; and on this presentation with a fracture of the distal tibia and fibula. To our knowledge, this is not documented in the literature and is a characteristic not documented in relation to Beals syndrome.