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Monmousseau F, Mulot L, Rusch E, Picon L, Laharie D, Fotsing G, Gargot D, Charpentier C, Buisson A, Trang-Poisson C, Dib N, DES Garets V, Brunet-Houdard S, Aubourg A. Predictors of each quality of life dimension in Crohn's disease patients initiating an anti-TNF treatment: differentiated effects of patient-, disease-, and treatment-related characteristics. Scand J Gastroenterol 2022; 57:566-573. [PMID: 35188859 DOI: 10.1080/00365521.2021.2025419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS In Crohn's disease (CD), a composite therapeutic target was recently recommended, including both objective measurement (endoscopic remission) and Patient-Reported Outcomes (resolution of abdominal pain and normalization of bowel function). All dimensions of health-related quality of life (HRQoL) are impacted: not only bowel symptoms but also systemic symptoms, emotional wellbeing and social function. Thus, understanding the predictors of each HRQoL dimension would improve patient management. However, analysis of these factors has only been found in a few publications, with some limitations. Therefore, this study aimed to explore the evolution of the HRQoL of CD patients during six months after initiation of anti-TNF and to identify its predictors. METHODS We analyzed data of 56 patients included in a multicenter prospective cohort study (COQC-PIT). HRQoL measures (using IBDQ-32) and data related to patient, disease and treatment characteristics were collected every two months. Generalized estimating equations were used. RESULTS Overall HRQoL was significantly improved 2 months after anti-TNF initiation, and then stagnated. Patient, disease, and treatment characteristics have differentiated impacts on the overall score and on each dimension of quality of life. Subcutaneous anti-TNF had no significant effect on overall HRQoL, improving only emotional function and bowel symptoms. Concomitant use of corticosteroids and/or immunomodulators impaired almost all dimensions. Having children or working altered bowel symptoms. Disease duration and active smoking negatively impact emotional function and systemic symptoms. CONCLUSIONS Each HRQoL dimension, not only bowel symptoms, and their influencing factors should therefore be considered in medical decision-making, especially in months following the initiation of a new treatment such as anti-TNF.
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Affiliation(s)
- Fanny Monmousseau
- Health-Economic Evaluation Unit, University Hospital Center of Tours, France.,EA7505 Education, Ethics, Health, University of Tours, Tours, France
| | - Lucile Mulot
- Health-Economic Evaluation Unit, University Hospital Center of Tours, France
| | - Emmanuel Rusch
- Health-Economic Evaluation Unit, University Hospital Center of Tours, France.,EA7505 Education, Ethics, Health, University of Tours, Tours, France
| | - Laurence Picon
- Gastroenterology Department, University Hospital Center of Tours, France
| | - David Laharie
- Gastroenterology Department, University Hospital Center of Bordeaux, France
| | - Ginette Fotsing
- Gastroenterology Department, University Hospital Center of Poitiers, France
| | - Dany Gargot
- Gastroenterology Department, Hospital Center of Blois, France
| | - Cloé Charpentier
- Gastroenterology Department, University Hospital Center of Rouen, France
| | - Anthony Buisson
- Gastroenterology Department, University Hospital Center of Clermont-Ferrand, France
| | | | - Nina Dib
- Gastroenterology Department, University Hospital Center of Angers, France
| | - Véronique DES Garets
- EA6296 VALLOREM, Loire Valley Management Research Unit, University of Tours, France
| | - Solène Brunet-Houdard
- Health-Economic Evaluation Unit, University Hospital Center of Tours, France.,EA7505 Education, Ethics, Health, University of Tours, Tours, France
| | - Alexandre Aubourg
- Gastroenterology Department, University Hospital Center of Tours, France
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- COQC-PIT Study Group: Dr Laura ARMENGOL DEBEIR, Dr Arnaud BOURREILLE, Juliette EVON, Margaux NISTAR, Geoffrey BERTHON
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Zhang M, Zhang T, Hong L, Zhang C, Zhou J, Fan R, Wang L, Wang Z, Xu B, Zhong J. Improvement of psychological status after infliximab treatment in patients with newly diagnosed Crohn's disease. Patient Prefer Adherence 2018; 12:879-885. [PMID: 29872273 PMCID: PMC5973631 DOI: 10.2147/ppa.s156883] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Patients with newly diagnosed Crohn's disease (CD) are associated with impaired physical and psychological well-being. These psychological characteristics are dynamic with the course of disease and could be influenced by medical treatment. Infliximab is effective and widely used in moderate-to-severe CD patients. The aim of this study was to evaluate the improvement of psychological status after infliximab treatment in patients with newly diagnosed CD. METHODS Newly diagnosed moderate-to-severe CD patients were prospectively enrolled in our study. Infliximab 5 mg/kg was administered at weeks 0, 2, 6, 14, 22, and 30. Outcomes including disease severity, illness perceptions, coping strategies, anxiety, depression, and quality of life (QoL) were measured at baseline, week 14, and week 30. RESULTS Eighty-two patients completed our study. The rates of clinical remission at weeks 14 and 30 were 59/82 (72.0%) and 58/82 (70.7%), respectively. Patients who achieved clinical remission at weeks 14 and 30 significantly improved in illness perceptions (P<0.001 and <0.001), maladaptive coping (P=0.005 and 0.004), anxiety (P<0.001 and <0.001), depression (P=0.004 and 0.004), and QoL (P<0.001 and <0.001). However, emotion-focused coping and problem-focused coping remained unchanged. For infliximab nonresponders, no significant changes were seen in illness perceptions, coping strategies, anxiety, depression, or QoL at week 14 or 30. CONCLUSION Effective infliximab treatment not only led to clinical remission in patients with newly diagnosed moderate-to-severe CD but also improved their psychological status including illness perceptions, maladaptive coping, anxiety, depression, and QoL.
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Affiliation(s)
- Maochen Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Tianyu Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Liwen Hong
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Chen Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Jie Zhou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Rong Fan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Lei Wang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Zhengting Wang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Bin Xu
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Correspondence: Jie Zhong; Bin Xu, Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197, Ruijiner Road, Shanghai 200025, People’s Republic of China, Tel +86 21 6437 0045 (ext 600907), Email ;
| | - Jie Zhong
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
- Correspondence: Jie Zhong; Bin Xu, Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197, Ruijiner Road, Shanghai 200025, People’s Republic of China, Tel +86 21 6437 0045 (ext 600907), Email ;
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Saro C, Ceballos D, Muñoz F, de la Coba C, Aguilar MD, Lázaro P, García-Sánchez V, Hernández M, Barrio J, de Francisco R, Fernández LI, Barreiro-de Acosta M. Clinical status, quality of life, and work productivity in Crohn's disease patients after one year of treatment with adalimumab. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:122-129. [PMID: 28026199 DOI: 10.17235/reed.2016.4600/2016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
OBJECTIVE Clinical trials have shown the efficacy of adalimumab in Crohn's disease, but the outcome in regular practice remains unknown. The aim of the study was to examine clinical status, quality of life, and work productivity of Crohn's disease patients receiving adalimumab for one year in the context of usual clinical practice. MATERIAL AND METHODS This was a prospective, observational study with a one-year follow-up. After baseline, Crohn's disease patients were evaluated at 1, 3, 6, 9, and 12 months after starting treatment with adalimumab. Outcome variables included: clinical status (measured with CDAI), quality of life (measured with EuroQoL-5D and IBDQ), and work productivity (measured with WPAI questionnaire). These outcome variables were compared using the Student's t test or Wilcoxon test for paired comparison data according to the data distribution. Statistical significance was set at two-sided p < 0.05. RESULTS The sample was composed of 126 patients (age [mean] 39.1 ± [standard deviation] 13.8 years; 51% male). Significant changes were observed during the follow-up period: CDAI decreased from [median] 194 ([25-75 percentiles] 121-269) to 48.2 (10.1-122.0) (p < 0.05); the EuroQoL-5D increased from 0.735 (0.633-0.790) to 0.797 (0.726-1.000) (p < 0.05); the EuroQoL-5D visual analogue scale increased from 50.0 (40-70) to 80.0 (60-90); (p < 0.05) and the IBDQ increased from 56.7 (51.6-61.5) to 67.5 (60.1-73.6) (p < 0.05). The total work productivity impact decreased from 53% to 24% (p < 0.05). CONCLUSIONS In regular practice, adalimumab is clinically effective in the treatment of Crohn's disease patients and results in a significant improvement in quality of life and work productivity.
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Affiliation(s)
| | | | - Fernando Muñoz
- Aparato digestivo, Complejo Asistencial Universitario de Salamanca, España
| | | | | | - Pablo Lázaro
- Advanced Techniques in Health Services Research. Madrid
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Subramaniam K, Fallon K, Ruut T, Lane D, McKay R, Shadbolt B, Ang S, Cook M, Platten J, Pavli P, Taupin D. Infliximab reverses inflammatory muscle wasting (sarcopenia) in Crohn's disease. Aliment Pharmacol Ther 2015; 41:419-28. [PMID: 25580985 DOI: 10.1111/apt.13058] [Citation(s) in RCA: 111] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Revised: 09/21/2014] [Accepted: 11/30/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Muscle wasting or sarcopenia arising from chronic inflammation is found in 60% of patients with Crohn's disease. Transcriptional protein NF-κB reduces muscle formation through MyoD transcription and increases muscle breakdown by proteolysis. AIM As TNF is a potent activator of NF-κB, and anti-TNF agent infliximab (IFX) prevents NF-κB activation, to determine whether or not Crohn's patients treated with IFX gain muscle volume and strength. METHODS We performed a prospective, repeated-measures cohort study in adult Crohn's disease patients with an acute disease flare. Patients were instructed not to vary diet or activity. Concomitant medications were kept stable. At week 1 (pre-treatment), week 16 (post-IFX induction) and week 25 (post-first IFX maintenance dose), we assessed (i) MRI volume of quadriceps femoris at anatomical mid-thigh; (ii) maximal concentric quadriceps contractions strength at three specific speeds of contraction; (iii) physical activity by validated instrument (IPAQ); (iv) Three-day food record of intake and composition (food-weighing method); (v) Serum levels of IL6. RESULTS Nineteen patients (58% female; mean age 33.2 ± 10.7 years) were recruited. IFX increased muscle volume in both legs from baseline (right, 1505 cm(3) ) to week 25 (right, 1569 cm(3) ; P = 0.010). IFX also increased muscle strength in both legs from baseline (right 30°/s, 184.8 Nm) to week 25 (right 30°/s, 213.6 Nm; P = 0.002). Muscle volume gain correlated with male gender (P = 0.003). Significant gains in muscle volume and strength were unrelated to prednisolone use. Serum IL6 levels decreased by week 25 (P = 0.037). CONCLUSION The anti-TNF agent infliximab reverses inflammatory sarcopenia in patients with Crohn's disease.
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Affiliation(s)
- K Subramaniam
- Gastroenterology and Hepatology Unit, Canberra Hospital, Garran, ACT, Australia
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Herrera-deGuise C, Casellas F, Robles V, Navarro E, Borruel N. Predictive value of early restoration of quality of life in Crohn's disease patients receiving antitumor necrosis factor agents. J Gastroenterol Hepatol 2015; 30:286-91. [PMID: 25302652 DOI: 10.1111/jgh.12803] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2014] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIM Crohn's disease (CD) impairs patients' health-related quality of life (HRQoL), therefore a goal of treatment is to improve their health. Recently, a more ambitious therapeutic target has been proposed, to reestablish patients' HRQoL to normal standards. There is no information on long-term prognostic value of restoring the health of patients with CD. Our aim was to determine if early restoration of HRQoL with antitumor necrosis factor (anti-TNF) agents is associated with long-term clinical remission. METHODS Retrospective longitudinal study in patients with active CD treated with anti-TNF agents. Patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ)-36 at baseline and weeks 2, 6, 14, 28, and 52. Early restoration of health was defined as an IBDQ-36 score > 209 at week 14, and long-term clinical remission as a Cohn's disease activity index (CDAI) score < 150 maintained through week 52. RESULTS Ninety-four patients were included. Sixty-three patients maintained long-term remission, with 47 (75%) of them achieving early restoration of HRQoL. Of the 31 patients who did not maintain long-term remission, only 4 (13%) restored their HRQoL early (P < 0.01). There was a strong negative correlation between the IBDQ-36 at week 14 and CDAI values at week 52 (rs = - 0.64, P < 0.01). Ninety-two percent of patients with early restoration of HRQoL maintained long-term remission versus 37% who did not restore their HRQoL (P < 0.01). To predict long-term remission, the cutoff point of 209 of the early IBDQ-36 had an area under the receiver operating characteristic (AUROC) curve of 0.87. CONCLUSION Achieving early restoration of HRQoL with anti-TNF agents is associated with sustained long-term remission. This could be a therapeutic goal of treatment in clinical trials and daily practice.
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Affiliation(s)
- Claudia Herrera-deGuise
- Unitat Atenció Crohn-Colitis (UACC), Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain
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Lim CS, Moon W, Park SJ, Park MI, Kim HH, Kim JB, Choi JM, Chang HK, Lee SH. A rare case of free bowel perforation associated with infliximab treatment for stricturing Crohn's disease. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 62:169-73. [PMID: 24077628 DOI: 10.4166/kjg.2013.62.3.169] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Crohn's disease is characterized by chronic transmural inflammation of the bowel and is associated with serious complications, such as bowel strictures, abscesses, fistula formation, and perforation. As neither medical nor surgical therapy provides a cure for Crohn's disease, the primary goals of therapy are to induce and maintain remission and prevent complications. As a biologic agent, infliximab, a monoclonal antibody to tumor necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease that does not respond to other medical therapies or surgery. Infliximab has proven to be very effective for inducing and maintaining remission in Crohn's disease; however, infliximab treatment has several potential complications. Here, we report a case of free perforation following a therapeutic response after an initial dose of infliximab for Crohn's disease. This is the first case report describing a free perforation in a Crohn's disease patient after an initial dose of infliximab.
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Affiliation(s)
- Chang Sup Lim
- Departments of Internal Medicine, Pathology, and Surgery, Institute for Medical Science, Kosin University College of Medicine, Busan, Korea
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Sherman M, Tsynman DN, Kim A, Arora J, Pietras T, Messing S, St Hilaire L, Yoon S, Decross A, Shah A, Saubermann L. Sustained improvement in health-related quality of life measures in patients with inflammatory bowel disease receiving prolonged anti-tumor necrosis factor therapy. J Dig Dis 2014; 15:174-9. [PMID: 24373601 DOI: 10.1111/1751-2980.12125] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to determine whether the effects of prolonged therapy (≥1 year) with anti-tumor necrosis factor (TNF) agents were sustained on the health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD). METHODS A cross-sectional survey of patients with IBD who were treated with anti-TNF agents was performed. Results of the validated HRQoL measures (inflammatory bowel disease questionnaire [IBDQ], EuroQoL-5 dimensions [EQ-5D], health status visual analogue scale [VAS] and the Zung self-rating depression scale) were recorded and compared between patients treated with anti-TNF agents for <1 year and ≥1 year. RESULTS A total of 41 patients were finally enrolled in the study. Among them, 11 (26.8%) had received anti-TNF therapy for less than one year with a median duration of 7 months (range 3-11 months), while the other 30 (73.2%) had been treated for ≥1 year with a median duration of 42 months (range 12-104 months). Crohn's disease was the most common type in both groups. None of the mean IBDQ, EQ-5D and EQ-5D plus VAS, or Zung self-rating depression scale scores differed significantly between the two groups of patients. CONCLUSIONS Improvements in HRQoL for IBD patients on anti-TNF therapy were sustained for longer than one year. HRQoL measures for IBD patients treated with anti-TNF therapy for <1 year do not differ significantly from those treated for ≥1 year, but a trend towards improved HRQoL measures with prolonged therapy can be obtained.
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Affiliation(s)
- Michael Sherman
- Department of Internal Medicine, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas, USA
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Guloksuz S, Wichers M, Kenis G, Russel MGVM, Wauters A, Verkerk R, Arts B, van Os J. Depressive symptoms in Crohn's disease: relationship with immune activation and tryptophan availability. PLoS One 2013; 8:e60435. [PMID: 23544139 PMCID: PMC3609785 DOI: 10.1371/journal.pone.0060435] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2012] [Accepted: 02/27/2013] [Indexed: 12/21/2022] Open
Abstract
Crohn's disease (CD) is associated with immune activation and depressive symptoms. This study determines the impact of anti-tumor necrosis factor (TNF)-α treatment in CD patients on depressive symptoms and the degree to which tryptophan (TRP) availability and immune markers mediate this effect. Fifteen patients with CD, eligible for anti-TNF-α treatment were recruited. Disease activity (Harvey-Bradshaw Index (HBI), Crohn's Disease Activity Index (CDAI)), fatigue (Multidimensional Fatigue Inventory (MFI)), quality of life (Inflammatory Bowel Disease Questionnaire (IBDQ)), symptoms of depression and anxiety (Symptom Checklist (SCL-90), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS)), immune activation (acute phase proteins (APP)), zinc and TRP availability were assessed before treatment and after 2, 4 and 8 weeks. Anti-TNF-α increased IBDQ scores and reduced all depression scores; however only SCL-90 depression scores remained decreased after correction for HBI. Positive APPs decreased, while negative APPs increased after treatment. After correction for HBI, both level and percentage of γ fraction were associated with SCL-90 depression scores over time. After correction for HBI, patients with current/past depressive disorder displayed higher levels of positive APPs and lower levels of negative APPs and zinc. TRP availability remained invariant over time and there was no association between SCL-90 depression scores and TRP availability. Inflammatory reactions in CD are more evident in patients with comorbid depression, regardless of disease activity. Anti-TNF-α treatment in CD reduces depressive symptoms, in part independently of disease activity; there was no evidence that this effect was mediated by immune-induced changes in TRP availability.
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Affiliation(s)
- Sinan Guloksuz
- Department of Psychiatry and Psychology, Maastricht University Medical Centre, EURON, Maastricht, The Netherlands.
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Bastida G, Nos P, Aguas M, Beltrán B, Iborra M, Ortiz V, Garrigues V, Estevan R, Ponce J. The effects of thiopurine therapy on health-related quality of life in Inflammatory Bowel Disease patients. BMC Gastroenterol 2010; 10:26. [PMID: 20196836 PMCID: PMC2846867 DOI: 10.1186/1471-230x-10-26] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2009] [Accepted: 03/02/2010] [Indexed: 01/02/2023] Open
Abstract
Background The effect of thiopurine immunomodulators on health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD) has been controversial. The aims were to evaluate the HRQoL in patients with IBD treated with thiopurines and assess the short- and long-term impacts of the treatment on HRQoL. Methods Ninety-two consecutive patients who started treatment with thiopurines were prospectively included. Evaluation of HRQoL was performed at months 0, 6, and 12 using two questionnaires, the Short-Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Results Baseline score of IBDQ was 4,6, range (2,31-6,84), with an impairment of the five dimensions of HRQoL compared with inactive patients. Results obtained in 8 dimensions of SF-36 showed worse HRQoL than Spanish general population. At 6 months patients had a significant improvement in overall IBDQ score -5,8 (1,58 -6,97)- and also in all IBDQ dimensions. All the 8 dimensions of SF-36 obtained a significant improvement. At twelve months score of IBDQ was 6,1, range (2,7-6,98), with improvement in all dimensions compared with baseline and 6 months. SF-36 showed a similar significant improvement in all subscales. Conclusions Thiopurine immunomodulators alone or with other treatments have a positive and long lasting impact on HRQoL of IBD patients.
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Affiliation(s)
- Guillermo Bastida
- Gastroenterology Unit, La Fe Hospital, Valencia, 21 Campanar Avenue, Valencia 46009, Spain.
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Ng SC, Plamondon S, Gupta A, Burling D, Kamm MA. Prospective assessment of the effect on quality of life of anti-tumour necrosis factor therapy for perineal Crohn's fistulas. Aliment Pharmacol Ther 2009; 30:757-66. [PMID: 19575762 DOI: 10.1111/j.1365-2036.2009.04088.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Anti-tumour necrosis factor (TNF) therapy effectively treats Crohn's perineal fistulas (CPF); the effect on health-related quality of life (HRQoL) remains unknown. AIMS To evaluate the effect of anti-TNF therapy on the HRQoL of patients with CPF in daily clinical practice. METHODS Prospective evaluation of clinical and magnetic resonance imaging (MRI) responses, disease activity (Perianal Disease Activity Index - PDAI), and HRQoL assessment [Inflammatory Bowel Disease Questionnaire (IBDQ)] in patients receiving anti-TNF therapy for CPF treated up to 12 months. RESULTS In all, 26 patients with CPF were treated (mean age 39 years; 19 infliximab, 7 adalimumab). At baseline, 85% patients had impaired IBDQ scores (mean 137; 'normal' >170). At 12 months, mean increases in IBDQ score for infliximab and adalimumab treated patients were 40 and 41 points respectively (P < 0.05). There were significant improvements in all IBDQ subscores (bowel, emotional, systemic, social) at 12 months (all P < or = 0.003). Fourteen patients (74%) on infliximab and six on adalimumab (86%) achieved IBDQ score > or =170. Mean increase in IBDQ score was 50, 34 and 16 points in patients with clinical fistula closure (P < 0.001), clinical response (P = 0.002) and no response (n = 1) respectively. IBDQ score increased for patients with MRI healing (P < 0.001) and MRI improvement (P = 0.016), but not for those with no MRI change (n = 2). IBDQ correlated significantly with PDAI at baseline and at 12 months. CONCLUSION Anti-TNF therapy improves HRQoL in patients with CPF at 12 months and this improvement is most pronounced in patients with clinical and MRI healing.
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Affiliation(s)
- S C Ng
- Department of Gastroenterology, St Mark's Hospital, London, UK
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Haapamäki J, Turunen U, Roine RP, Färkkilä MA, Arkkila PET. Finnish patients with inflammatory bowel disease have fewer symptoms and are more satisfied with their treatment than patients in the previous European survey. Scand J Gastroenterol 2008; 43:821-30. [PMID: 18584521 DOI: 10.1080/00365520801912011] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Symptoms associated with inflammatory bowel diseases (IBD) have a negative impact on quality of life. The purpose of this study was to assess the quality of life in a large group of Finnish IBD patients and to compare it with that observed in a recent survey covering several other European countries. MATERIAL AND METHODS The European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) questionnaire, comprising questions about IBD symptoms, diagnosis, therapy, extraintestinal manifestations and their impact on patients' quality of life, was sent to 3852 members of the Finnish Crohn and Colitis Association. The response rate was 63%. RESULTS IBD was diagnosed by a specialist in over 96% of cases and 94% of patients were continuously followed-up by a specialist. Fifty-eight percent of the patients had had IBD symptoms for over a year before consulting a specialist. The frequency of symptoms was lower in the Finnish patients and 93% of patients were satisfied with their current treatment compared with 76% in the European survey. For Crohn's disease, the rate of surgery was lower than that in the European survey (43% versus 52%). The patients reported improved quality of life after surgery, but 67% of patients with Crohn's disease and 34% with ulcerative colitis reported recurrence of symptoms. Comorbidity with ankylosing spondylitis was 22 times more common than in the general Finnish population and 49% of the patients suffered from joint pain. CONCLUSIONS Finnish IBD patients are more satisfied with their treatment than those studied in the European survey. In Finland, gastroenterologists are usually responsible for the care, but the delay before the diagnosis remains long.
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Affiliation(s)
- Johanna Haapamäki
- Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Group Administration, Helsinki and Uusimaa Hospital District, Finland.
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González-Lama Y, López-San Román A, Marín-Jiménez I, Casis B, Vera I, Bermejo F, Lázaro Pérez-Calle J, Taxonera C, Martínez-Silva F, Menchén L, Martínez-Montiel P, Calvo M, Antonio Carneros J, López P, Luis Mendoza J, María Milicua J, Huerta A, Sánchez F, Abreu L, López-Palacios N, Maté J, Gisberta JP. Open-label infliximab therapy in Crohn's disease: a long-term multicenter study of efficacy, safety and predictors of response. GASTROENTEROLOGIA Y HEPATOLOGIA 2008; 31:421-6. [DOI: 10.1157/13125587] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Rutgeerts P, Schreiber S, Feagan B, Keininger DL, O'Neil L, Fedorak RN. Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha, improves health-related quality of life in patients with moderate to severe Crohn's disease. Int J Colorectal Dis 2008; 23:289-96. [PMID: 18071721 PMCID: PMC2225995 DOI: 10.1007/s00384-007-0395-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/17/2007] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Certolizumab pegol, a polyethylene glycolated Fc-free Fab' was efficacious and well tolerated in patients with moderate-to-severe Crohn's disease in a previously reported randomized, placebo-controlled study. In this paper, we report the effect of certolizumab pegol on health-related quality of life (HRQoL). MATERIALS AND METHODS Patients with moderate-to-severe active Crohn's disease (n = 292) received subcutaneous certolizumab pegol 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. A post hoc analysis of the intent-to-treat population (290 patients with HRQoL data) assessed HRQoL by evaluating patients' responses to the self-administered inflammatory bowel disease questionnaire (IBDQ) at baseline and weeks 2, 4, 6, 8, 10, and 12. RESULTS Patients receiving certolizumab pegol 400 mg at weeks 0, 4, and 8 demonstrated, via their IBDQ total score, significantly (P <or= 0.05) greater improvement in HRQoL from baseline to week 12 and at all other time points compared with placebo. Moreover, HRQoL improved over time in all certolizumab pegol groups, irrespective of baseline C-reactive protein levels. Emotional well-being (IBDQ Emotional Function domain) improved throughout the study for patients receiving certolizumab pegol 400 mg. This improvement was significantly (P <or= 0.05) greater than for patients receiving placebo at all time points. In addition, systemic symptoms (IBDQ Systemic Symptoms domain) improved significantly more in patients receiving certolizumab pegol 400 mg than in those receiving placebo at weeks 4, 8, 10, and 12 (P <or= 0.05) and approached statistical significance at week 2 (P = 0.054). CONCLUSION This analysis suggests that certolizumab pegol 400 mg improves HRQoL in patients with moderate-to-severe Crohn's disease.
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Affiliation(s)
- Paul Rutgeerts
- Division of gastroenterology, University Hospital Leuven, Leuven, Belgium.
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Casellas F, Rodrigo L, Niño P, Pantiga C, Riestra S, Malagelada JR. Sustained improvement of health-related quality of life in Crohn's disease patients treated with infliximab and azathioprine for 4 years. Inflamm Bowel Dis 2007; 13:1395-400. [PMID: 17567874 DOI: 10.1002/ibd.20205] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Infliximab induces remission and improves the health-related quality of life (HRQOL) of patients with refractory or fistulous Crohn's disease (CD). However, little information is available as to whether its effect on HRQOL is sustained over time. The objective was to measure the HRQOL of CD patients in long-term clinical remission. METHODS Prospective, observational study was undertaken in patients with CD in infliximab-induced clinical remission (Harvey index <3) for at least 6 months, and receiving long-term infliximab and azathioprine maintenance therapy. Patients were followed for 4 years or until clinical relapse (Harvey index >3). HRQOL was assessed annually using the validated Spanish version of the disease-specific 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) and the EuroQol-5D. RESULTS Forty-nine patients with CD in stable clinical remission were included at baseline. At 12 months, n = 42 patients remained in remission, at 24 months n = 32 patients, at 36 months n = 13, and in the last visit at 48 months 6 patients remained in clinical remission. The overall score on the IBDQ-36 remained unchanged in patients with stable, inactive CD (median overall score of 6.1 at baseline and 6.5 at 4 years). Scores on all 5 dimensions of the IBDQ-36 remained unchanged over the study period in stable patients. Patients in remission scored highly on the preference value ratings of the EuroQol-5D (scores of 1.0) and remained unchanged in patients who remained in remission. CONCLUSIONS Sustained clinical remission of CD achieved with maintenance treatment maintains HRQOL over long-term follow-up.
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Affiliation(s)
- Francesc Casellas
- Unitat d'Atenció Crohn-Colitis from Hospital Universitari Vall d' Hebron, Spain.
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Zisman TL, Kane SV. Current and future therapies for inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2007; 1:89-100. [PMID: 19072438 DOI: 10.1586/17474124.1.1.89] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The introduction of biologic agents to the therapeutic arsenal has dramatically impacted the way we treat patients with inflammatory bowel disease, allowing clinicians to achieve lasting remission in patients who are unresponsive to conventional therapies. New research continues to expand our understanding of the inflammatory cascade of ulcerative colitis and Crohn's disease, revealing a host of potential therapeutic targets for intervention. As we look toward the future in this rapidly developing field, we must learn how best to incorporate these new agents into the treatment algorithm to enhance or replace conventional therapies.
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Affiliation(s)
- Timothy L Zisman
- Clinical Research Fellow in Gastroenterology, The University of Chicago Hospitals, 5841 S. Maryland Avenue MC 4076, Chicago, IL 60637, USA.
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Thomas T, Cohen RD. Pharmacoeconomic considerations for inflammatory bowel disease in the era of biological therapies. Expert Rev Gastroenterol Hepatol 2007; 1:101-12. [PMID: 19072439 DOI: 10.1586/17474124.1.1.101] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The biological therapies have revolutionized the ability to treat patients with inflammatory bowel disease. While these therapies have proven efficacy, they are not without significant medication expense. This has raised the question of whether society can afford these new therapies. Costs associated with inflammatory bowel disease have focused traditionally on direct costs of disease, with the greatest contributions due to surgeries and hospitalization. Initial investigations suggest that biologics can reduce healthcare utilization and their associated costs. Additionally, the importance of indirect costs and improvements in quality of life must also be considered when examining the cost efficiency of these new therapeutic modalities, which may result in a cost savings for our healthcare system.
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Affiliation(s)
- Tojo Thomas
- University of Chicago Hospitals, 5841 S. Maryland Avenue MC 4076, Chicago, IL 60637, USA.
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17
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Gao Q, Meijer MJW, Schlüter UG, van Hogezand RA, van der Zon JM, van den Berg M, van Duijn W, Lamers CBHW, Verspaget HW. Infliximab treatment influences the serological expression of matrix metalloproteinase (MMP)-2 and -9 in Crohn's disease. Inflamm Bowel Dis 2007; 13:693-702. [PMID: 17243139 DOI: 10.1002/ibd.20100] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) are actively involved in the pathogenesis of Crohn's disease (CD). We assessed the effect of the anti-tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody infliximab on the in vitro and in vivo expression of MMP-2 and MMP-9 in CD. METHODS Infliximab-treated fistulizing (n = 10) or active disease (n = 7) CD patients, from an in-house study, and fistulizing CD patients (n = 42) and active CD patients (n = 24) from 2 placebo controlled studies were evaluated for serum MMP levels and clinical response. Biopsies were evaluated immunohistochemically for the MMPs. Whole blood cultures stimulated with lipopolysaccharide (LPS)/infliximab were evaluated for MMP mRNA and protein levels. RESULTS Serum MMP-2 levels in CD patients increased during follow-up, similarly in responders and nonresponders, by infliximab. Immunohistochemistry showed no clear MMP-2 change in biopsies. Serum MMP-9 levels, however, showed a consistent pattern of decrease in most CD patients, particularly in those responding, and MMP-9-positive polymorphonuclear leukocytes in biopsies also decreased by infliximab. LPS stimulation of whole blood increased the MMP-9 levels in plasma significantly in CD patients and controls, but infliximab had no effect on the secretion. Long-term LPS stimulation raised leukocyte MMP-9 mRNA levels 16-fold and infliximab inhibited this induction by 80%. CONCLUSIONS Infliximab treatment increases MMP-2 and decreases MMP-9 in serum of patients with CD, the latter also in the intestine, which extends and confirms our previous ex vivo explants observations. However, these changes were not strictly associated with the response to treatment. The enhanced leukocyte MMP-9 expression in CD seems to be regulated by TNF-alpha.
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Affiliation(s)
- Qiang Gao
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands
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18
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Zisman TL, Cohen RD. Pharmacoeconomics and quality of life of current and emerging biologic therapies for inflammatory bowel disease. ACTA ACUST UNITED AC 2007; 10:185-94. [PMID: 17547857 DOI: 10.1007/s11938-007-0012-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The development of biologic therapies for Crohn's disease and ulcerative colitis has profoundly affected the treatment of these diseases. The impact of these novel therapies has been tremendous in terms of their ability to cause clinical improvement in symptoms and endoscopic and histologic evidence of healing, as well as improvements in quality of life. However, the success of these new remedies comes with a significant price tag. In the current cost-containment environment of health care, it is essential to evaluate the impact of these novel and promising therapies on health care resource utilization, employment productivity, and quality of life. Despite the high cost of these new medications, they may result in a net cost savings through their ability to induce remission in the sickest of inflammatory bowel disease (IBD) patients, thereby averting the large expenditures associated with hospitalization and surgery. Likewise, by improving patients' physical symptoms, emotional well-being, and quality of life, biologic agents have the potential to reduce much of the unemployment, missed work, and disability through which IBD patients suffer. In a disease with an early age of onset and a chronic course with normal life expectancy, reducing morbidity and improving quality of life should be important measures of treatment success. Biologic therapies for IBD hold significant promise in this regard, allowing clinicians to achieve lasting remission in patients who are unresponsive to conventional therapies. Comparison of the costs and benefits of biologic therapies with conventional treatments for IBD is complicated by the need to assess the downstream effects of an intervention. For example, corticosteroids are inexpensive and very effective for induction of remission, but they come with significant long-term complications, such as osteoporosis, cataracts, impaired glucose tolerance, and poor wound healing, which must be taken into account when assessing their true cost as a maintenance medication. We do not yet have enough experience with biologic therapies to evaluate their potential to prevent or create future costs associated with adverse effects. However, as we move forward with our knowledge of biologic agents, an understanding of the economic and quality-of-life implications of these innovative therapies is crucial for patients, clinicians, and third-party payers alike.
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Affiliation(s)
- Timothy L Zisman
- Russell D. Cohen, MD The University of Chicago Hospitals, 5841 South Maryland Avenue, MC 4076, Chicago, IL 60637, USA.
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Minderhoud IM, Samsom M, Oldenburg B. Crohn’s disease, fatigue, and infliximab: Is there a role for cytokines in the pathogenesis of fatigue? World J Gastroenterol 2007; 13:2089-93. [PMID: 17465453 PMCID: PMC4319130 DOI: 10.3748/wjg.v13.i14.2089] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn’s disease (CD) patients.
METHODS: Fourteen CD patients were blinded for treatment and received placebo at baseline, and infliximab 2 wk later, with a follow-up of 4 wk. Blood samples were drawn on a regular basis, and questionnaires on fatigue, depression, quality of life, and clinical disease activity were completed at regular intervals.
RESULTS: After placebo infusion, fatigue scores decreased within 3 d (3.5 points ± 1.1, P≤ 0.01), but returned to baseline values 14 d after this infusion. The drop of fatigue scores following infliximab infusion sustained until the end of the study (3.8 points ± 1.4, P≤ 0.05). Quality of life was increased at the end of the study compared to baseline values (138.6 ± 9.4 vs 179.4 ± 6.7; P≤ 0.005), whereas depression scores were decreased (20.4 ± 9.4 vs 11.3 ± 2.2; P≤ 0.01). No correlation between the severity of fatigue and the level of cytokines was observed.
CONCLUSION: The reduction of fatigue after infliximab infusion is subjective to a placebo effect. The effect of infliximab on fatigue, however, persists while the placebo effect disappears after a short period of time. A clear role of cytokines could not be substantiated.
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Affiliation(s)
- Itta M Minderhoud
- Department of Gastro-enterology, Univerisity Medical Centre Utrecht, Utrecht, The Netherlands
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Cohen RD, Thomas T. Economics of the use of biologics in the treatment of inflammatory bowel disease. Gastroenterol Clin North Am 2006; 35:867-82. [PMID: 17129818 DOI: 10.1016/j.gtc.2006.09.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The introduction of the biologic therapies into the therapeutic regiment for IBD, coupled with the vast changes seen in health care delivery within the past decade, have turned previous economic assumptions and models on their head, and opened up a new opportunity to redefine what is truly the cost of a disease, and of its' interventions. Pundits and pencil-pushers are quick to point to the high drug cost as a threat to the economic stability of the health care system, without first doing a carefully planned, balanced analysis of the overall impact that such a therapy will make on the entire cost-structure of the system. This is also true outside of the United States, where those who must budget and pay for the therapies do not pay for the use of health care services, and simply enter the drug costs on an accountant's debit sheet. Such analyses are complicated, because they must calculate the impact that such therapies have on the direct costs of health care and the indirect costs for both the patient and their families or health care support system. Realizing what impact these therapies might have on altering the natural history of these previously relentless chronic debilitating conditions, and redefining how normal quality of life can actually get on these therapies, should be the focus of future studies as clinicians try to calculate truly whether these agents are cost savings for society overall.
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Affiliation(s)
- Russell D Cohen
- Section of Gastroenterology, Department of Medicine, University of Chicago Medical Center, MC 4076, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
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Calvet X, Gallardo O, Coronas R, Casellas F, Montserrat A, Torrejón A, Vergara M, Campo R, Brullet E. Remission on thiopurinic immunomodulators normalizes quality of life and psychological status in patients with Crohn's disease. Inflamm Bowel Dis 2006; 12:692-6. [PMID: 16917223 DOI: 10.1097/00054725-200608000-00004] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Thiopurinic immunomodulators are effective for maintaining symptom remission in Crohn's disease. Little is known, however, about their effect on patients' quality of life or psychological well-being. The present study aimed to determine whether remission induced by thiopurinic immunomodulators returns levels of quality of life and psychological well-being to normal. MATERIALS AND METHODS A case-control study was performed. Cases were 33 patients with Crohn's disease treated with azathioprine or 6-mercaptopurine and in stable remission for at least 6 months. Sixty-six healthy individuals matched 2:1 by age and sex and 14 patients with active Crohn's disease were included as control groups. Quality of life was evaluated with the Short Form (SF-36) questionnaire, and the respective Hamilton rating scales were used for anxiety and depression. ANOVA with Bonferroni's correction was used for multiple comparisons. RESULTS SF-36 global scores were 85 in the study group, 85 in healthy controls (P = 1), and 58.6 in patients with active disease (P < 0.001 for the comparison with the other 2 groups). The differences between values were 0 (95% CI -4-4), 26.4 (95% CI 20-32), and 26.4 (95% CI 19-33), respectively. The respective anxiety and depression scores were 6.5, 5.5, and 16.2 and 3.7, 3.3, and 10.9. No significant differences were observed in any of the SF-36 domains between case and control groups, whereas in patients with active disease, all domains were significantly worse. CONCLUSIONS Thiopurinic immunomodulator-induced remission restores normal levels of quality of life and psychological well-being in Crohn's disease patients.
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Affiliation(s)
- Xavier Calvet
- Unitat de Malalties Digestives, Hospital de Sabadell, Institut Universitari Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain.
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Rutgeerts P, Van Assche G, Vermeire S. Review article: Infliximab therapy for inflammatory bowel disease--seven years on. Aliment Pharmacol Ther 2006; 23:451-63. [PMID: 16441465 DOI: 10.1111/j.1365-2036.2006.02786.x] [Citation(s) in RCA: 124] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Infliximab, the chimeric monoclonal IgG1 antibody to tumour necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and extra-intestinal manifestations of inflammatory bowel disease. Recently, the active ulcerative colitis trials (ACT) studies have shown that infliximab is also efficacious to treat ulcerative colitis resistant to standard therapy. Induction with 5 mg/kg infliximab at weeks 0, 2 and 6 is advocated. The response to infliximab is improved when concomitant immunosuppressive therapy is given. As the majority of patients will relapse if not retreated, a long-term strategy is necessary. Although episodic therapy can be used, the optimal strategy is systematic maintenance treatment with 5 mg/kg intravenous (i.v.) every 8 weeks. Long-term maintenance therapy with infliximab results in a reduction of the rate of complications, hospitalizations and surgeries associated with Crohn's disease. Safety problems with the monoclonal antibody infliximab treatment mainly concern the formation of antibodies to infliximab, which may lead to infusion reactions, loss of response and serum sickness-like delayed infusion reactions. Latent tuberculosis needs to be screened for. The rate of other opportunistic infections is slightly increased mainly in patients treated concomitantly with immunosuppression. There is no evidence that malignancy rates in patients treated with antitumour necrosis factor strategies are increased.
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Affiliation(s)
- P Rutgeerts
- Department of Medicine, Division of Gastroenterology, University of Leuven, Leuven, Belgium.
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Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine involved in a wide range of important physiologic processes. This cytokine has a pathologic role in some diseases, and TNF-alpha antagonists are effective in treating inflammatory conditions. Given the putative role of TNF-alpha in host defense against tuberculosis and other infections, the risk of infection with TNF-alpha antagonists is a concern. Therefore, we searched the literature for reports of tuberculosis and other infections associated with TNF-alpha-antagonist therapy. Although tuberculosis was rarely reported in randomized clinical comparisons of these antagonists, case reports and submissions to the MedWatch program of the United States Food and Drug Administration have been numerous. Most instances were associated with infliximab, but etanercept and adalimumab may also be associated with an increased risk of tuberculosis. Histoplasmosis, listeriosis, aspergillosis, coccidioidomycosis, and candidiasis have been associated with TNF-alpha antagonists, but the causative relationship is not clear. Potential recipients of these drugs should be rigorously screened with skin testing, detailed questioning about recent travel and potential tuberculosis exposure, assessment for symptoms such as cough and weight loss, and chest radiography to minimize their risk of acquiring or reactivating tuberculosis. As with other immunosuppressant drugs, TNF-alpha antagonists should not be given to patients with active infection.
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Affiliation(s)
- David J Rychly
- College of Pharmacy, University of Georgia, Athens, Georgia, USA
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Gao Q, Hogezand RA, Lamers CBHW, Verspaget HW. Basic fibroblast growth factor as a response parameter to infliximab in fistulizing Crohn's disease. Aliment Pharmacol Ther 2004; 20:585-92. [PMID: 15339330 DOI: 10.1111/j.1365-2036.2004.02126.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Fibroblast growth factors play an important role in (patho)physiological processes such as wound healing and tissue repair. We previously showed that basic fibroblast growth factor is actively involved in inflammatory bowel disease processes. In the present retrospective study, we assessed whether serum basic fibroblast growth factor levels in Crohn's disease patients reflect the response to anti-tumour necrosis factor-alpha antibody infliximab treatment. AIM AND METHODS Serum samples, biopsies and patient data from a subgroup of patients included in two placebo-controlled trials were used. Fistulizing Crohn's disease patients (n = 42) were administered placebo or infliximab intravenously three times and evaluated for response up to 18 weeks. Biopsies from a subgroup of patients were stained for basic fibroblast growth factor using indirect immunohistochemistry. In the active Crohn's disease trial, patients (n = 24) received either placebo or infliximab once, and disease activity and serum basic fibroblast growth factor were assessed at weeks 0 and 4. RESULTS Basic fibroblast growth factor levels at inclusion were comparable in the fistulizing Crohn's disease patients regardless of whether the fistulas did or did not respond or completely heal (median range: 9.3-10.6 pg/mL). At the end of follow-up basic fibroblast growth factor levels were lower in patients who responded (9.2 pg/mL, P = 0.06) or who were completely healed (8.9 pg/mL, P = 0.009) when compared with patients did not respond/heal (14.5 pg/mL), the latter not significantly increased from baseline. Decreases in the perianal disease activity index and open fistula scores at the end of the follow-up were significantly correlated with the decrease in basic fibroblast growth factor (R = 0.41; P = 0.012 and R = 0.35; P =0.027, respectively). Immunohistological evaluation also showed a trend towards decreased basic fibroblast growth factor expression in intestinal biopsies of these patients. Patients with active disease, i.e. a Crohn's disease activity index > or = 220 combined from the two studies, were found to have significantly (P = 0.0046) lower baseline serum basic fibroblast growth factors levels than those with inactive disease (5.3 vs. 10.3 pg/mL, respectively). Treatment of the active disease patients did not affect the serum basic fibroblast growth factor level, although a general decrease in disease activity was observed with infliximab treatment. CONCLUSIONS Healing of fistulizing/perianal Crohn's disease seems to be reflected by a decrease in high serum basic fibroblast growth factor. Basic fibroblast growth factor levels do not relate with response in active Crohn's disease patients.
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Affiliation(s)
- Q Gao
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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D'Ovidio V, Aratari A, Viscido A, Pimpo MT, Caprilli R, Torchio P. Infliximab and quality of life in steroid-dependent Crohn's disease. Dig Liver Dis 2004; 36:557-8. [PMID: 15334780 DOI: 10.1016/j.dld.2004.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Abstract
Infliximab, the chimeric monoclonal immunoglobulin (Ig)G1 antibody to tumor necrosis factor (TNF) has changed our therapy of Crohn's disease. Infliximab is indicated in refractory luminal and fistulizing Crohn's disease. In patients with luminal disease, a single intravenous (i.v.) dose of 5 mg/kg is efficacious; in fistulizing disease, an i.v. loading therapy of 5 mg/kg at weeks 0, 2, and 6 is advocated. Because the majority of patients will relapse if not re-treated, a long-term strategy is necessary. The optimal long-term approach is systematic re-treatment with 5 mg/kg every 8 weeks. Episodic therapy on relapse also is possible but is less efficacious and frequently is associated with problems resulting from the formation of antibodies to infliximab (ATI). If treatment is episodic, maintenance therapy with immunosuppression (azathioprine [AZA]/6-mercaptopurine [6-MP] or methotrexate) is mandatory. Trial data suggest that systematic maintenance with 8 weekly doses of infliximab decreases the rate of complications, hospitalizations, and surgeries. These effects probably are achieved thanks to thorough healing of the bowel. Infliximab also is indicated in treating corticosteroid-dependent Crohn's disease and extraintestinal manifestations of Crohn's disease. There are no data yet that support its use as first-line therapy. The data in ulcerative colitis (UC) are conflicting and we should await the results of 2 large controlled trials (ACT1 and ACT2) to position infliximab in the treatment of UC. Other anti-TNF strategies have been less effective than infliximab in the treatment of IBD until now. The results with thalidomide are promising but much more research into small molecules inhibiting TNF and other proinflammatory cytokines is necessary. Safety problems with antibody treatment mainly concern immunogenicity leading to infusion reactions, loss of response, and serum sickness-like delayed infusion reactions. The rate of opportunistic infections is increased mainly in patients treated concomitantly with immunosuppression. Other adverse events associated with anti-TNF strategies are demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased.
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Affiliation(s)
- Paul Rutgeerts
- Department of Medicine, Division of Gastroenterology, University of Leuven, Belgium.
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