Background: Fatigue is the third most prevalent symptom for patients with inflammatory bowel disease (IBD), yet optimal strategies for its management are unclear. Treatment protocols for fatigue in other conditions have been based on cognitive-behavioural models. Targeting cognitions, emotions and behaviour related to fatigue through cognitive-behavioural therapy (CBT) may be a viable option to improve fatigue and quality of life (QoL) in IBD. Methods: This single centre, two-arm, feasibility randomised controlled trial (RCT) aimed to assess the feasibility and initial estimates of potential efficacy of a CBT intervention for the management of IBD-fatigue. Feasibility, acceptability and initial estimates of potential efficacy outcomes were collected through self-report measures and semi-structured interviews. Participants were recruited from one tertiary referral centre. Intervention Group 1 received a CBT manual for fatigue, one 60-min and seven 30-min telephone sessions with a therapist over 8-weeks. Control Group 2 received a fatigue information sheet without therapist support. A nested qualitative study evaluated patients' and therapists' experiences, and IBD-healthcare professionals' (HCPs) perceptions of the intervention. Results: Eighty-nine participants were assessed for eligibility. Of these, 31 of the 70 eligible participants consented to participate (recruitment rate of 44%). Of the 15 participants randomised to the intervention group, 13 (87%) started it and 10 (77% of those who started) completed all 8 sessions. Follow-up questionnaires were completed by 22 (71%) participants at 3 months, 14 (45%) at 6 months and 12 (39%) at 12 months' follow-up. The intervention was acceptable to participants and feasible for therapists to deliver. HCPs reported that the intervention would be applicable, but time, finance and training constraints limit its implementation. Initial estimates of potential efficacy with complete case analysis showed a reduction in fatigue and an increase in QoL at 3, 6 and 12 months post-randomisation. Conclusions: A full-scale effectiveness RCT testing CBT for IBD-fatigue is feasible and is potentially worthwhile with some changes to the protocol. However, given the small numbers, further pilot work is warranted before a full-scale RCT.
BACKGROUND: Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm.
METHODS: CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week). De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met. The primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers 48 weeks after randomisation. Primary and safety analyses were done in the intention-to-treat population. This trial has been completed, and is registered with ClinicalTrials.gov, number NCT01235689.
FINDINGS: Between Feb 11, 2011, and Nov 3, 2016, 244 patients (mean disease duration: clinical management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group). 29 (24%) patients in the clinical management group and 32 (26%) patients in the tight control group discontinued the study, mostly because of adverse events. A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 (56 [46%] of 122 patients) than in the clinical management group (37 [30%] of 122 patients), with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1% (95% CI 3·9-28·3; p=0·010). 105 (86%) of 122 patients in the tight control group and 100 (82%) of 122 patients in the clinical management group reported treatment-emergent adverse events; no treatment-related deaths occurred. The most common adverse events were nausea (21 [17%] of 122 patients), nasopharyngitis (18 [15%]), and headache (18 [15%]) in the tight control group, and worsening Crohn's disease (35 [29%] of 122 patients), arthralgia (19 [16%]), and nasopharyngitis (18 [15%]) in the clinical management group.
INTERPRETATION: CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone. Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability.
FUNDING: AbbVie.
BACKGROUND: Ingestion of AndoSan™, based on the mushroom Agaricus blazei Murill, has previously been shown to exhibit anti-inflammatory effects because of reduction of pro-inflammatory cytokines in healthy individuals and patients with ulcerative colitis. In this randomized single-blinded placebo controlled study we examined whether intake of AndoSan™ also resulted in clinical effects.
METHODS AND FINDINGS: 50 patients with symptomatic ulcerative colitis were block-randomized and blinded for oral daily intake of AndoSan™ or placebo for the 21 days' experimental period. The patients reported scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSan™ group (n = 24) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.88 (4.92-6.83), 4.71 (3.90-5.52) (p = 0.002) and 4.50 (3.70-5.30) (p = 0.001). Corresponding improved mean scores (±SD) for total fatigue were 16.6 (5.59), 14.1 (4.50) (p = 0.001) and 15.1 (4.09) (p = 0.023). These scores in the placebo group (n = 26) were not improved. When comparing the two study groups using mixed model statistics, we found significant better scores for the AndoSan™-patients. HRQoL for dimensions bodily pain, vitality, social functioning and mental health improved in the AndoSan™ group. There were no alterations in general blood samples and fecal calprotectin.
CONCLUSIONS: Beneficiary effects on symptoms, fatigue and HRQoL from AndoSan™ consumption were demonstrated in this per-protocol study, supporting its use as a supplement to conventional medication for patients with mild to moderate symptoms from ulcerative colitis. The patients did not report any harms or unintended effects of AndoSan™ in this study.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01496053.
Background Ingestion of AndoSanTM , based on the mushroom Agaricus blazei Murill, has previously shown an anti-inflammatory effect through reduction of pro-inflammatory cytokines in healthy individuals and patients with Crohn's disease (CD). In this randomized single-blinded placebo-controlled study we examined whether intake of AndoSanTM also resulted in clinical effects. Methods and Findings50 patients with symptomatic CD were randomized for oral daily consumption of AndoSanTM or placebo for a 21-day experimental period, in this per-protocol study. Patients reported validated scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSanTM group (n = 25) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.52 (4.64-6.40), 4.48 (3.69-5.27) and 4.08 (3.22-4.94) (p<0,001). We found significant improvements in symptom score for both genders in the AndoSanTM group, and no significant changes in the placebo (n = 25) group. There were however no significant differences between the groups (p = 0.106), although a marginal effect in symptom score for men (p = 0.054). There were comparable improvements in physical, mental and total fatigue for both groups. HRQoL versus baseline were at day 21 improved for bodily pain and vitality in the AndoSanTM group and for vitality and social functioning in the placebo group. No crucial changes in general blood samples and fecal calprotectin were detected. Conclusions The results from this single-blinded randomized clinical trial shows significant improvement on symptoms, for both genders, in the AndoSanTM group, but no significant differences between the study groups. The results on fatigue, HRQoL, fecal calprotectin and blood samples were quite similar compared with placebo. The patients did not report any harms or unintended effects of AndoSanTM . CD patients with mild to moderate symptoms may have beneficiary effects of AndoSanTM as a safe supplement in addition to conventional medication.TRIAL REGISTRATION ClinicalTrials.gov NCT01496053
ANTECEDENTES: La anemia por deficiencia de hierro (IDA) se ve con frecuencia en la enfermedad inflamatoria intestinal. Tradicionalmente, los suplementos de hierro por vía oral está vinculada a importantes efectos secundarios gastrointestinales y la posible exacerbación de la enfermedad. Este estudio multicéntrico de fase 3 a prueba la eficacia y seguridad de maltol férrico, un complejo de hierro férrico (Fe) con maltol (3-hidroxi-2-metil-4-pirona), como una nueva terapia de hierro por vía oral para la AIF.
Métodos: Los pacientes adultos con reposo o de leve a moderada colitis ulcerosa o enfermedad de Crohn, de leve a moderada de la AIF (9,5 a 12,0 g dl y 9,5 a 13,0 g / dl en mujeres y hombres, respectivamente /), y documentado en el fracaso anteriores productos de hierro orales recibieron cápsulas orales férricos maltol (30 mg dos veces al día) o placebo idéntico durante 12 semanas según un, doble ciego, el diseño del estudio aleatorizado controlado con placebo. La variable principal de eficacia fue el cambio en la hemoglobina (Hb) desde el inicio hasta la semana 12. Se evaluaron la seguridad y la tolerabilidad.
Resultados: De los 329 pacientes seleccionados, 128 terapia aleatorio recibida (64 pacientes tratados con placebo maltol tratados y 64 férricos) y agrupados en el análisis de eficacia por intención de tratar: 55 pacientes férricos maltol (86%) y 53 pacientes tratados con placebo (83% ) completaron el ensayo. Mejoras significativas en la Hb se observaron con maltol férrico versus placebo en las semanas 4, 8 y 12: media (SE) 1,04 (0,11) g / dl, 1,76 (0,15) g / dL, y 2,25 (0,19) g / dl, respectivamente (p <0,0001 en todos los puntos de tiempo, análisis de covarianza). Hb se normalizó en dos tercios de los pacientes a la semana 12. El perfil de seguridad de maltol férrico era comparable con el placebo, sin impacto en la gravedad de la enfermedad inflamatoria intestinal.
CONCLUSIONES: maltol férrico siempre rápidas mejorías clínicamente significativas en la Hb y mostró un perfil de seguridad favorable, lo que sugiere su posible uso como una alternativa al hierro intravenoso en la enfermedad inflamatoria intestinal AIF.
OBJECTIVE: To assess the effectiveness of solution-focused therapy (SFT) on fatigue and quality of life (QoL) in patients with fatigued inflammatory bowel disease (IBD).
DESIGN: Randomised controlled trial in two Dutch hospitals. Patients with IBD with quiescent IBD and with a Checklist Individual Strength--Fatigue (CIS--fatigue) score of ≥ 35 were enrolled. Patients were 1:1 randomised to receive SFT or care as usual (CAU) for 3 months. Patients were followed for a further 6 months after the SFT. Primary endpoint was defined as changes in fatigue and QoL during follow-up. Secondary endpoints included change in anxiety and depression, medication use, side effects to medication, disease activity, laboratory parameters (C-reactive protein, leucocytes and haemoglobin) and sleep quality.
RESULTS: Ninety-eight patients were included, of whom 63% were women, mean age was 40.1 years. After the SFT course, 17 (39%) patients in the SFT group had a CIS-fatigue score below 35 compared with eight (18%) of patients in the CAU group (p=0.03). The SFT group also showed a greater reduction in fatigue across the first 6 months compared with the CAU group (CIS-fatigue: p=<0.001 and CIS-total: p=0.001). SFT was associated with a significant higher mean IBD questionnaire change at 3 months (p=0.020). At 9 months, no significant differences between the two groups were observed.
CONCLUSIONS: SFT has a significant beneficial effect on the severity of fatigue and QoL in patients with quiescent IBD. However, this effect diminished during follow-up.
ANTECEDENTES: bloqueo-Gut selectiva de tráfico de linfocitos por Vedolizumab puede constituir un tratamiento efectivo para la colitis ulcerosa.
MÉTODOS: Llevamos a cabo dos ensayos doble ciego de Vedolizumab integrados aleatorizados, controlados con placebo en pacientes con enfermedad activa. En el ensayo de la terapia de inducción, 374 pacientes (cohorte 1) recibieron Vedolizumab (a una dosis de 300 mg) o placebo por vía intravenosa en las semanas 0 y 2, y 521 pacientes (cohorte 2) recibieron abierto Vedolizumab en las semanas 0 y 2, con la evaluación de la enfermedad en la semana 6. En el ensayo de la terapia de mantenimiento, los pacientes en cualquiera de cohorte que tenía una respuesta a Vedolizumab en la semana 6 fueron asignados al azar para continuar recibiendo Vedolizumab cada 8 o 4 semanas o para cambiar a un placebo durante un máximo de 52 semanas. Una respuesta se definió como una reducción en la puntuación de la Clínica Mayo (rango, 0 a 12, con las puntuaciones más altas indican una enfermedad más activa) de al menos 3 puntos y una disminución de al menos el 30% del valor inicial, con una disminución de acompañamiento en el recto sangrado subpuntuación de al menos 1 punto o un absoluto subpuntuación sangrado rectal de 0 o 1.
RESULTADOS: Las tasas de respuesta en la semana 6 fueron 47,1% y 25,5% entre los pacientes del grupo Vedolizumab y grupo placebo, respectivamente (diferencia con el ajuste para los factores de estratificación, 21,7 puntos porcentuales; 95% intervalo de confianza [IC], 11,6-31,7; P < 0.001). En la semana 52, el 41,8% de los pacientes que continuaron recibiendo Vedolizumab cada 8 semanas y el 44,8% de los pacientes que continuaron recibiendo Vedolizumab cada 4 semanas estaban en remisión clínica (puntuación clínica Mayo ≤2 y no subpuntuación> 1), en comparación con 15,9 % de los pacientes que cambiaron a placebo (diferencia ajustada, 26,1 puntos porcentuales para Vedolizumab cada 8 semanas versus placebo [IC del 95%, 14,9-37,2; P <0,001] y 29.1 puntos porcentuales para Vedolizumab cada 4 semanas frente a placebo [95% IC, 17,9-40,4; P <0,001]). La frecuencia de eventos adversos fue similar en los grupos Vedolizumab y placebo.
CONCLUSIONES: Vedolizumab fue más eficaz que el placebo como tratamiento de inducción y mantenimiento de la colitis ulcerosa. (Financiado por Millennium Pharmaceuticals;. GÉMINIS 1 número ClinicalTrials.gov, NCT00783718).
Background: Fatigue is the third most prevalent symptom for patients with inflammatory bowel disease (IBD), yet optimal strategies for its management are unclear. Treatment protocols for fatigue in other conditions have been based on cognitive-behavioural models. Targeting cognitions, emotions and behaviour related to fatigue through cognitive-behavioural therapy (CBT) may be a viable option to improve fatigue and quality of life (QoL) in IBD. Methods: This single centre, two-arm, feasibility randomised controlled trial (RCT) aimed to assess the feasibility and initial estimates of potential efficacy of a CBT intervention for the management of IBD-fatigue. Feasibility, acceptability and initial estimates of potential efficacy outcomes were collected through self-report measures and semi-structured interviews. Participants were recruited from one tertiary referral centre. Intervention Group 1 received a CBT manual for fatigue, one 60-min and seven 30-min telephone sessions with a therapist over 8-weeks. Control Group 2 received a fatigue information sheet without therapist support. A nested qualitative study evaluated patients' and therapists' experiences, and IBD-healthcare professionals' (HCPs) perceptions of the intervention. Results: Eighty-nine participants were assessed for eligibility. Of these, 31 of the 70 eligible participants consented to participate (recruitment rate of 44%). Of the 15 participants randomised to the intervention group, 13 (87%) started it and 10 (77% of those who started) completed all 8 sessions. Follow-up questionnaires were completed by 22 (71%) participants at 3 months, 14 (45%) at 6 months and 12 (39%) at 12 months' follow-up. The intervention was acceptable to participants and feasible for therapists to deliver. HCPs reported that the intervention would be applicable, but time, finance and training constraints limit its implementation. Initial estimates of potential efficacy with complete case analysis showed a reduction in fatigue and an increase in QoL at 3, 6 and 12 months post-randomisation. Conclusions: A full-scale effectiveness RCT testing CBT for IBD-fatigue is feasible and is potentially worthwhile with some changes to the protocol. However, given the small numbers, further pilot work is warranted before a full-scale RCT.
