Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis:First case

We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn’s disease at a different institution,although the clinical and radiological picture was not typical and the response to corticosteroids was poor.We performed a single-balloon enteroscopy showing a short,ulcerous stenosis 50 cm proximal from Bauhin’s valve.The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis(CMUSE).High dose corticosteroids were again started,without effect.The monoclonal tumor necrosis factor-α(TNF-α) antibody infliximab was added to the medical therapy.After induction therapy,both clinical and endoscopic amelioration was obtained.Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.     

Comparison of in-office magnetic resonance imaging versus conventional radiography in detecting changes in erosions after one year of infliximab therapy in patients with rheumatoid arthritis

Abstract

The objective of this study was to compare standard hand radiographs with in-office 0.2?T magnetic resonance imaging (MRI) in monitoring response to therapy in patients with rheumatoid arthritis (RA) who were receiving infliximab, to evaluate the frequency and location of erosions, and to determine if there were differences in outcome based on disease duration at baseline. Patients who satisfied the American College of Rheumatology criteria for RA and were receiving infliximab therapy were evaluated with a baseline and 1-year follow-up MRI. Magnetic resonance images were interpreted by two blinded, board-certified radiologists. Bone erosions were identified as well-defined defects extending through the cortical margin. The mean age of the 48 patients was 58.5 years. The median infliximab dosage was 4?mg/kg. Baseline data showed that 41 patients had abnormal MRIs. The mean time between the baseline and follow-up MRI examinations was 10.5 months. Follow-up MRI revealed regression in 11 patients. Thirty-one patients had both MRIs and radiographs. Magnetic resonance imaging was approximately twice as sensitive as radiography in detecting erosions at baseline. In-office MRI was useful in monitoring disease response after the initiation of infliximab treatment. Magnetic resonance imaging is potentially a very valuable diagnostic tool and prognostic indicator for use in patients with RA.     

Does perioperative biological therapy increase 30-day post-operative complication rates in inflammatory bowel disease patients undergoing intra-abdominal surgery? A systematic review

BackgroundBiopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice.MethodsA systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/2019.The population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intra-abdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle–Ottowa scale.Results2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNFα exposure while vedolizumab increased SSI and small bowel obstruction.ConclusionProspective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population.     

Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn’s disease

AIM:To investigate the correlation between rs1568885,rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn’s disease(CD).METHODS:One hundred and twenty-six patients diagnosed with CD based on standard clinical,endoscopic,radiological,and pathological criteria were enrolled in this study at the Gastroenterology Unit of the 2nd Department of Surgery and at the Colorectal Unit of the1st Department of Propaedeutic Surgery.Infliximab at a dose of 5 mg/kg was administered intravenously at weeks 0,2,6 and then every 8 wk.Clinical and serological responses were assessed using the HarveyBradshaw Index and serum C-reactive protein(CRP)levels,respectively,and the endoscopic response was evaluated by ileocolonoscopy performed at baseline and after 12-20 wk of therapy.The changes in endoscopic appearance compared to baseline were classified into four categories,and patients were classified as responders and non-responders.Genomic DNA from whole peripheral blood was extracted and genotyping was performed by allele-specific polymerase chain reactions.χ2test with Yate’s correction based on the S-Plus was used to compare the genotype frequencies.RESULTS:Eighty patients(63.49%)were classified as complete and 32(25.39%)as partial responders to infliximab,while 14(11.11%)were primary non-responders.No correlation was found between response to infliximab and patients’characteristics such as age,gender and disease duration.There was consistency between Harvey-Bradshaw index scores and serum CRP levels.The TT genotype of the rs1568885 polymorphism was significantly related to partial response(P=0.024)and resistance to infliximab(P=0.007)while the AT genotype was more frequent in partial responders(P=0.035)and in primary non-responders(P=0.032).Regarding rs1813443,the CC genotype was found to be associated with partial response(P=0.005)and primary resistance(P=0.002)to infliximab while no association was found between the rs4411591 polymorphism and the clinical response to infliximab.CONCLUSION:Based on our results,the rs1568885and rs1813443 polymorphisms are associated with clinical and biochemical response to infliximab in Greek patients with Crohn’s disease.     

Efficacy of infliximab in acute severe ulcerative colitis:A single-centre experience

AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included.Data were extracted from clinical records in order to assess response to IFX therapy.The primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse events.Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were compared.RESULTS:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis.The median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with < 1 year of follow-up,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of IFX.Overall,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of follow-up.There was one death from post-operative sepsis,20 d after a single IFX infusion.Colectomy rates were generally lower among those "bridging" to thiopurine.Of 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study end.No predictors of response were identified.CONCLUSION:IFX is effective for acute severe ulcerative colitis in real-life clinical practice.Two-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.     

Reevaluation of antibody titers 1 year after influenza vaccination in patients with rheumatoid arthritis receiving TNF blockers

Abstract

The aim of this study was to estimate the effective administration procedure of fondaparinux for prevention of venous thromboembolism after cemented total hip replacement (THR) in Japanese patients. The study included 471 Japanese patients. The dose regimens were 2.5 mg daily for 14 days (2.5 mg/14 day group) or 10 days (2.5 mg/10 day group), 1.5 mg daily for 10 days (1.5 mg group), 2.5 mg daily for the first 3 postoperative days and 1.5 mg daily for the subsequent 7 days (Mixed group), and no administration of fondaparinux (Control group). Deep venous thrombosis (DVT) was diagnosed by ultrasonography on postoperative day 3 or 4 and day 14. The 2.5 mg/14 day, 2.5 mg/10 day and Mixed groups were regarded as one group in the assessment on postoperative day 3 or 4, and denoted as the 2.5 mg group. The incidence of DVT on postoperative day 3 or 4 in the 2.5 mg group was significantly lower than that in the Control and 1.5 mg groups. On postoperative day 14, the incidence of DVT in the 1.5 mg and Mixed groups was significantly lower than that in the Control group in both the intention-to-treat and per-protocol analyses. The incidence in the 2.5 mg/10 day and 2.5 mg/14 day groups was significantly lower than that in the Control group in only the per-protocol analysis. The results suggest that the administration protocol of the Mixed group is effective in preventing DVT in Japanese patients undergoing cemented THR.     

Infliximab trough levels and persistent vs transient antibodies measured early after induction predict long-term clinical remission in patients with inflammatory bowel disease

BackgroundThe use of therapeutic drug monitoring has been proposed as a useful tool in the management of patients with loss of response to biological therapy in patients with inflammatory bowel disease.AimsTo evaluate whether early, post-induction anti-tumor necrosis factor trough levels and the presence of different types of anti-drug antibodies may impact long-term clinical remission in patients with inflammatory bowel disease.MethodsWe prospectively assessed anti-tumor necrosis factor trough levels and both persistent and transient anti-drug antibodies. The Harvey–Bradshaw Index and the partial Mayo score were evaluated at each visit or in case of relapse.ResultsAt week 14, median infliximab trough levels were significantly lower in patients who experienced loss of response at week 48 as compared to patients in stable remission (1.3 mcg/mL [range 0–10.2 mcg/mL] vs. 10.1 mcg/mL[range 0–42.8 mcg/mL], P < 0.0004). ROC curve identified an infliximab trough levels of 6.2 mcg/mL as the cut-off value with the highest accuracy (c-index = 0.864) for loss of response at week 48. At week 14 we observed a correlation between anti-drug antibodies concentration and infliximab trough levels (r_s = −0.513, P = 0.04).ConclusionsThe results highlight the usefulness of assessing early biological TL in order to predict patients’ long-term outcome.