Adipose-Derived Therapeutic Products for the Management of Refractory Crohn's Fistula

International audienc

Monitoring of infliximab trough levels and anti-infliximab antibodies in inflammatory bowel diseases: A comparison of three commercially available ELISA kits

International audienc

Long-term Safety and Efficacy of Local Microinjection Combining Autologous Microfat and Adipose-Derived Stromal Vascular Fraction for the Treatment of Refractory Perianal Fistula in Crohn’s Disease

International audienc

First clinical case report of local microinjection of autologous fat and adipose-derived stromal vascular fraction for perianal fistula in Crohn’s disease

Abstract Mesenchymal stem cell therapy is a promising treatment for perianal Crohn’s fistulas refractory to conventional therapy, which are an extremely morbid complication and a true therapeutic challenge. Autologous adipose-derived stromal vascular fraction (ADSVF) is an easily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. Here, we describe a case involving a patient with severe perianal Crohn’s fistulas refractory to the best medical and surgical practices who received local treatment with ADSVF and microfat. This patient was first examined under anesthesia with drainage via seton placement; 1 week later, on a single day, he underwent adipose tissue extraction, ADSVF and microfat preparation, and the local injection of 14 ml of microfat and approximately 20 million viable ADSVF cells into the soft tissue around the fistulas. No serious adverse events were observed. At the first endpoint at 12 weeks, the fistula had clinically healed with complete re-epithelialization of all external openings; no fistula tract was detected on magnetic resonance imaging, confirming this finding. This good clinical outcome was sustained at 48 weeks and was associated with a reduction in the severity of perianal disease and an improvement in quality of life. The current case highlights the therapeutic potential of a new cellular treatment for Crohn’s patients with refractory perianal fistulas based on the innovative hypothesis that the combined action of ADSVF in association with the trophic characteristics of a microfat graft could be beneficial for this condition. Trial registration: EudraCT number 201325, NCT02520843 . Registered on 5 August 201

Real-World Comparison of the Effectiveness between Ustekinumab and Vedolizumab in Patients with Ulcerative Colitis Exposed to at least One Anti-TNF Agent

International audienceBackground Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking. Aim We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients. Patients and Methods In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]. Results Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39–3.13], p = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [p = 0.52], 44.4% vs 33.8% [p = 0.52], and 2.6% vs 19.1% [p = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25–11.36], p = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47–23.30], p = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51–2.08], p = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11–0.82], p = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab. Conclusion While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC

Three-year outcome of local injection of autologous stromal vascular fraction cells and microfat in refractory perianal fistulas of Crohn’s disease

International audienceAbstract Perianal fistulas in Crohn's disease are frequent and disabling, with a major impact on patients' quality of life. Cell-based therapy using mesenchymal stem cells represents new hope for these patients, but long-term efficacy remains challenging. In a pilot study, including patients with refractory complex perianal fistulas, autologous adipose-derived stromal vascular fraction (ADSVF) combined with microfat achieved combined remission in 60% of cases, with a good safety profile at 1 year. The purpose of this study is to assess whether these results were maintained at longer term. The safety and efficacy data of the ten patients were evaluated retrospectively 3 years after injection on the basis of clinical and radiological data. MRI were analysed according to the MAGNIFI-CD score. No adverse event was attributed to the experimental stem-cell treatment. Combined remission was achieved in 7 patients (70%) and associated with a significant improvement in the MAGNIFI-CD MRI score. In conclusion, the safety and efficacy of ADSVF and microfat injection in Crohn's disease fistulas were maintained at 3 years, demonstrating that this innovative strategy is effective in producing a long-lasting healing effect. The ongoing multicentre randomized placebo-controlled trial (NCT04010526) will be helpful to define the place for this approach in the current therapeutic arsenal

Tofacitinib as salvage therapy for 55 patients hospitalised with refractory severe ulcerative colitis: A GETAID cohort

International audienceSummary Background Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In patients hospitalised for severe flare, who previously experienced multiple drug failures, including steroids and anti‐TNF agents, new quick‐acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid onset of action. Aim To evaluate effectiveness and safety of tofacitinib as rescue therapy in patients hospitalised for UC flare. Methods We conducted an observational and multicentre study with both retrospective and prospective collections in 14 GETAID centres. The primary objective was to assess the survival without colectomy following tofacitinib initiation in patients hospitalised for a UC flare. We determined rates of clinical response, clinical remission, and steroid‐free clinical remission at week 6 and week 14 and safety. Results Fifty‐five patients were included (49 with prior infliximab failure and 19 previously exposed to ciclosporin). With a median follow‐up of 6.5 months (interquartile range [IQR] [3‐12.3]), rate of colectomy‐free survival was estimated at 78.9% (95 CI [68.5‐90.9]) and 73.6% (95 CI [61.9‐87.3]) at 3 and 6 months, respectively. Rates of clinical response, clinical remission and steroid‐free clinical remission were 60%, 45.5% and 37.5% at week 6 and 41.8%, 34.5% and 32.7% at week 14. Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zoster infections occurred in patients aged over 60 years old. No venous thrombotic or major adverse cardiovascular events occurred. Conclusion Tofacitinib appears as a promising option in patients hospitalised with a UC flare but needs further validation in controlled trials

Long-term efficacy and safety of ustekinumab in refractory Crohn's disease patients: a multicenter retrospective experience

International audienc

Long-term efficacy and safety of ustekinumab in refractory Crohn's disease patients: a multicenter retrospective experience

International audienc

Maintenance of remission among patients with inflammatory bowel disease after vedolizumab discontinuation: a multicentre cohort study

International audienceBackground and aim - It is unclear whether vedolizumab therapy can be discontinued in patients with inflammatory bowel disease [IBD] after achieving steroid-free clinical remission. The aim was to assess the risk of relapse after vedolizumab therapy was discontinued. Methods - This was a retrospective observational study, collecting data from 21 tertiary centres affiliated with the GETAID from January 2017 to April 2019. Consecutive patients with IBD, who were in steroid-free clinical remission for at least 3 months and were treated with vedolizumab for at least 6 months, were included at the time of vedolizumab discontinuation. Results - A total of 95 patients [58 with Crohn's disease] discontinued vedolizumab after a median duration of therapy of 17.5 [10.6-25.4] months. After a median follow-up period of 11.2 [5.8-17.7] months, 61 [64%] patients experienced disease relapse. The probabilities of relapse-free survival were 83%, 59%, and 36% at 6, 12, and 18 months, respectively. According to the multivariate analysis, a C-reactive protein level less than 5 mg/L at vedolizumab discontinuation (hazard ratio [HR] = 0.56, 95% confidence interval [CI] [0.33-0.95], p = 0.03) and discontinuation due to patients' elective choice (HR = 0.41, 95% CI [0.21-0.80], p = 0.009) were significantly associated with a lower risk of relapse. Re-treatment with vedolizumab was noted in 24 patients and provided steroid-free clinical remission in 71% and 62.5% at Week 14 and after a median follow-up of 11.0 [5.4-13.3] months, respectively, without any infusion reactions. Conclusions - In this retrospective study, two-thirds of patients with IBD treated with vedolizumab experienced relapse within the first year after vedolizumab discontinuation. Re-treatment with vedolizumab was effective in two-thirds of patients