Crohnin taudin hoitovasteen arviointi ja seuranta

In Crohn s disease (CD), achievement of mucosal healing has been associated with good outcome. The role of clinical indices such as the Harvey-Bradshaw index (HBI) and surrogate inflammatory markers such as C-reactive protein (CRP) and faecal calprotectin to indicate mucosal healing is unsettled. Studies on predictive markers for endoscopic outcome in CD treated with anti-tumour necrosis factor-α antibodies (anti-TNF) are also limited. Retrospective data on 71 infliximab-treated patients (Study I) and prospective data on 42 either adalimumab- or infliximab-treated patients (Study II) underwent analysis to identify features predicting one-year endoscopic outcome. Study III analyzed retrospective data on 60 inflammatory bowel disease patients, including 34 with CD, to assess the predictive role of calprotectin measured after anti-TNF induction. Study IV included prospective data on 210 endoscopies to assess the power of surrogate markers and clinical indices to detect mucosal healing. Among patients receiving anti-TNF as maintenance therapy, 12-month mucosal healing was significantly more common in those patients who had presented 3-month mucosal healing, than in those with endoscopically active disease at 3 months. A normal calprotectin after anti-TNF induction was associated with, although without statistical significance, one-year endoscopic remission. Calprotectin was superior to CRP and clinical indices in detecting mucosal healing. However, although calprotectin alone identified endoscopic remission with 84% sensitivity and 74% specificity, it was beaten, but not statistically significantly, by a new combined index based on calprotectin and the HBI. In anti-TNF-treated active luminal CD, endoscopic remission at 3 months is a predictor for maintenance of the endoscopic response at one year. In patients on anti-TNF therapy, a normal faecal calprotectin after anti-TNF induction is a predictor of sustained clinical remission. A score based on a combination of calprotectin and the HBI may function as a new tool for identifying endoscopic remission. For optimisation of anti-TNF therapy in active luminal CD in clinical practice, these results suggest an objective inflammatory activity assessment such as ileocolonoscopy or determination of faecal calprotectin, performed as early as 3 months after initiation of therapy.Crohns sjukdom är en kronisk tarminflammation som oftast drabbar tjocktarmen och slutet av tunntarmen. Vanliga symtom är buksmärta, viktminskning, blodig avföring och diarré, vilket i värsta fall leder till arbetsoförmåga. Sjukdomen kan behandlas med antikroppar mot tumörnekrosfaktor α (anti-TNF), en i många fall riskabel behandling som endast en del patienter drar nytta av. Forskning visar att en i koloskopi påvisbar läkning av tarmslemhinnan är starkt kopplad till en gynnsam prognos. Uppföljningen av behandlingsresponsen är dock utmanande, eftersom tarmslemhinnans inflammatoriska aktivitet inte nödvändigtvis korrelerar med patientens subjektiva symtom. Eftersom koloskopi är en tidskrävande, dyr och ibland smärtsam undersökning, har man utvecklat ersättande noninvasiva metoder för att uppskatta sjukdomsaktiviteten. Surrogatmarkörers, bland annat det fekala kalprotektinets, förmåga att upptäcka endoskopiskt påvisbar slemhinneläkning är dock otillräckligt utredd. Likaså är prognostiska faktorer för långvarig slemhinneläkning under anti-TNF-behandling bristfälligt klarlagda. Avhandlingsprojektet bestod av fyra delarbeten (I-IV). För att identifiera faktorer kopplade till långvarig slemhinneläkning analyserades både retrospektivt (I: 71 patienter, III: 60 patienter) och prospektivt (II: 42 patienter) insamlade uppföljningsdata från patienter med anti-TNF-behandlad Crohns sjukdom. Utöver detta utreddes möjligheter att ersätta koloskopi med surrogatmarkörer och kliniska symtomindex (IV: data från sammanlagt 210 endoskopiundersökningar). Slemhinneläkning tre månader efter att behandlingen börjat var en stark prognostisk markör för fortsatt slemhinneläkning vid ett år. Ett normalt fekalt kalprotektin efter cirka tre månaders behandling förutspådde också en gynnsam ettårsprognos. Fekalt kalprotektin var den bästa enskilda surrogatmarkören för att upptäcka slemhinneläkning vid samma tidpunkt. Ett nytt, av forskningsgruppen utvecklat kombinerat aktivitetsindex som består av ett kliniskt aktivitetsindex och kalprotektin, uppvisade en ännu högre sensitivitet och specificitet för att upptäcka slemhinneläkning. Koloskopi eller kalprotektinmätning tre månader efter att behandlingen börjat optimerar anti-TNF-behandlingen vid Crohns sjukdom. Ett noninvasivt kombinationsindex bestående av ett symtomindex och kalprotektin kan bidra till att de begränsade koloskopiresurserna koncentreras till de patienter som verkligen behöver genomgå koloskopi

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn's disease patients in Finland

Background Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. Methods Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. Results Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. Conclusions Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification.Peer reviewe

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn's disease patients in Finland

Background Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland.Methods Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability.Results  Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period.Conclusions Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification.</div

Ustekinumab for Crohn’s disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn?s Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD.Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48?CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey?Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn?s disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up.Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p?=?.0001) and SES-CD from 12 to 3 (p?=?.009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up.Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.Peer reviewe

Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed

Tofacitinib real-world experience in ulcerative colitis in Finland (FinTofUC) : a retrospective non-interventional multicenter patient chart data study

Objectives The aim was to define the effectiveness of tofacitinib and to characterize the patient population receiving tofacitinib in a real-world cohort clinical setting for ulcerative colitis (UC) in Finland. Methods This is a retrospective non-interventional multicenter patient chart data study conducted in 23 Finnish Inflammatory Bowel Disease (IBD) centers. Baseline demographic and clinical data, clinical remission, steroid-free remission rate and time to tofacitinib discontinuation, colectomy or UC-related hospitalization were studied. Results The study included 252 UC patients of which 69% were male. Most patients had extensive disease (71%) and were bio-experienced (81%). Tofacitinib demonstrated positive treatment outcomes with clinical response, clinical remission, and steroid-free clinical remission at one year in 33%, 34% and 31% of patients, respectively. Moreover, 64% of patients in pMayo remission at week 16 from the start of tofacitinib were still in remission at one year. Only no or mild disease activity compared to moderate activity at baseline was associated with a higher probability of achieving remission according to pMayo at six months, p = .008. Hospitalizations and/or colectomies during the study period (before treatment discontinuation/end of follow-up) were low (n = 24), with less than 5 colectomies. Conclusions In this real-world cohort, including a majority of bio-experienced UC patients, tofacitinib was effective in achieving steroid-free clinical remission in a third of the population at one year. A majority of patients in remission at week 16 were also in remission at one year. Results are in line with earlier published real-world studies. Registration: ClinicalTrials.gov NCT05082428

Real-life treatment persistence and treatment outcomes of Finnish patients with inflammatory bowel disease receiving vedolizumab as first-line biological treatment

Purpose: To analyze treatment persistence and treatment outcomes of vedolizumab as first-line biological treatment in Crohn's disease (CD) and ulcerative colitis (UC) patients in a Finnish real-world setting. Methods: Observational, retrospective, multi-center chart review study that included adult CD and UC patients initiating vedolizumab as first-line biological treatment between 2014 and 2020. Results: The cohort consisted of 54 CD and 69 UC patients. At month 12, treatment persistence was 84.9 % in CD and 64.7 % in UC. Most vedolizumab discontinuations (CD, n = 11; UC, n = 26) were due to inefficacy. Discontinuations due to adverse events were rare (n < 5). Efficacy improvements were observed in treatment persistent patients at 12 months vs. baseline in the Harvey-Bradshaw Index (CD, 1.8 vs. 3.9, p = 0.001), Partial Mayo Score (UC, 1.0 vs. 4.9, p < 0.001), Physician's Global Assessment (CD, 0.9 vs. 1.8, p < 0.001; UC, 0.4 vs. 2.1, p < 0.001), along with positive endoscopic and biochemical outcomes. Clinical remission was 90.9 % vs. 63.0 % for CD, and 81.6 % vs. 12.3 % for UC, while corticosteroid use was 15.9 % vs. 53.7 % for CD, and 14.6 % vs. 92.8 % for UC at 12 months and baseline, respectively. Conclusion: Vedolizumab was associated with improvements in efficacy, endoscopic activity, biochemical parameters, and decreased corticosteroid burden when used as a first-line biological treatment.Peer reviewe