Marc Stelle | Université de Genève (original) (raw)
Papers by Marc Stelle
Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimm... more Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimmunity. The gastro-intestinal tract (GIT) is frequently involved with any segment being potentially affected from mouth to anus. The esophagus is the most common localization resulting in reflux and its complications such as erosive esophagitis and Barrett's esophagus. Gastric involvement is less frequent but may be complicated by hemorrhage due to gastric antral vascular ectasia (GAVE or watermelon stomach). Intestinal involvement may lead to malabsorption, intestinal pseudo-obstruction or bacterial overgrowth. Anorectal involvement can cause fecal incontinence and rectal prolapse. GIT involvement greatly affects morbimortality in SSc and therapeutic approaches essentially aim at relieving the symptoms
Systemic sclerosis (SSc) is a protean disorder in which prognosis and treatment are tailored on t... more Systemic sclerosis (SSc) is a protean disorder in which prognosis and treatment are tailored on the basis of organ involvement. Among SSc lung manifestations, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) or the combination of both, are the first cause of SSc mortality and impact heavily on patient quality of life. ILD may begin early in disease and usually progresses slowly. However, approximately 10% of patients with ILD may reach terminal respiratory insufficiency. PAH may be an early or late complication of SSc in which increased blood pressure in pulmonary arteries leads to right heart failure. Current treatments provide some benefit, but both SSc-ILD and PAH still represent an enormous unmet need of more efficacious therapeutic strategies
Revue médicale suisse, Jan 16, 2014
Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimm... more Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimmunity. The gastro-intestinal tract (GIT) is frequently involved with any segment being potentially affected from mouth to anus. The esophagus is the most common localization resulting in reflux and its complications such as erosive esophagitis and Barrett's esophagus. Gastric involvement is less frequent but may be complicated by hemorrhage due to gastric antral vascular ectasia (GAVE or watermelon stomach). Intestinal involvement may lead to malabsorption, intestinal pseudo-obstruction or bacterial overgrowth. Anorectal involvement can cause fecal incontinence and rectal prolapse. GIT involvement greatly affects morbimortality in SSc and therapeutic approaches essentially aim at relieving the symptoms.
La gazette médicale - info@gériatrie, 2018
Les réactions alimentaires indésirables sont une plainte fréquente dans la population générale. S... more Les réactions alimentaires indésirables sont une plainte fréquente dans la population générale. Selon les études épidémiologiques, environ 20% à 30% des personnes interrogées rapportent en souffrir. Ces réactions peuvent être classifiées selon leur mécanisme, soit immunologique (allergie alimentaire), non-immunologique (intolérance alimentaire) ou toxique. Bien qu’il n’y ait pas de données précises, les intolérances alimentaires seraient en augmentation, phénomène probablement amplifié par une forte couverture médiatique. Cet article a pour but d’énoncer les principales réactions alimentaires chez l’adulte, de discuter de la procédure diagnostique et des traitement
self-applied adhesion declaration and self-medication. An activity index was calculated on the sp... more self-applied adhesion declaration and self-medication. An activity index was calculated on the spot (Harvey-Bradshaw/Truelove) Results: Mean age was 41.3±11 years, 60% were women. The number of years since IBD diagnosis was 8±7; 64% were Crohn's disease (71% inactive), 36% ulcerative colitis (70% inactive). A 66% was treated with aminosalicylates, 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBD-related surgical procedure. A 69% (95%CI: 60-77%) showed some type of non-adhesion. A 66% (57-75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (9-22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (17-33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95%CI 1.1-8.4; p= 0.03) and feeling little informed about their disease (OR 4.9; 95%CI 1.1-23.8; p=0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95%CI 0.11-0.74; p=0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion W1221 AIM: Azathioprine (AZA) is frequently used in inflammatory bowel disease (IBD) for inducing and maintaining remission, sparing the use of steroids. The treatment must be withdrawn in 15% of patients due to the occurrence of adverse events, often related to the genetic background of the patients. Side effects are dose-independent (allergic reactions, idiosyncrasies) or dose-dependent (myelotoxicity, hepatitis, cancer). Aim of this study has been to investigate the prevalence of adverse effects, type and time of onset of AZA in a large series of Italian IBD patients, from a single centre. MATERIALS AND METHODS: Two thousand and fourteen consecutive IBD out-patients, referred to our Institution, were retrospectively studied. AZA was prescribed to 297 patients, 137 (46.1%) affected by ulcerative colitis (UC) and 160 (53.9%) by Crohn's disease (CD). One hundred and sixty-one (54.2%) were male and 136 (45.8%) female (average age of 32.38 +/-13.33 SD years, range 10-75 y.). RESULTS: Seventy-seven patients (26%) discontinued the treatment due to side effects, 39 with UC, and 38 with CD, with a respective prevalence of 28.5 % and 23,7%. The side effects was classified as dose independent 14.6% and dose dependent 13.9% in UC patients (one patient died due to severe leucopenia) and dose independent 10% and 13.7% dose dependent in CD patients. Side effects were observed after a mean period of 14.5 +/-20.3 SD months (range 0.5-123 m.). One hundred and fifty-three patients (51.5%) are still under treatment with AZA. The dose was reduced in 20 patients (13.1%) following the occurrence of mild side effects (3.9% dose independent and 9.2% dose dependent), 133 (86.9%) are still under treatment at full dosage. Thirty-six patients (12.1%) stopped therapy after obtaining stable remission, while 24 (8.1%), due to treatment failure. CONCLUSIONS: The prevalence of side effects leading to the withdrawal of AZA treatment was higher (26%) than that usually reported (15%). This higher prevalence may be attributed to genetic factors (prevalence of the phenotypic expression of the TPMT gene or other enzymes involved in AZA metabolism). The differing cut-off levels of leucocyte/lymphocyte considered at risk and leading to the suspension of treatment or reduction of dosage may also be responsible for discordance. Eleven percent of patients showed dose dependent effects 12 months from the onset of therapy, casting doubt on the adherence to the treatment schedule, at least in a subset of patients. Nonetheless this observation prompts prolonging clinical and biochemical controls over the usual six-month period.
Journal of Crohn's and Colitis, 2009
The increasing number of trials testing management strategies for luminal Crohn's disease (CD) ha... more The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not filled all the gaps in our knowledge and thus, in clinical practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence. Methods: A multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroiddependent (ST-D) and steroid-refractory (ST-R) CD. Results: Overall, 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated. In anti-TNF naïve patients, budesonide and prednisone were found to be appropriate for mild-moderate CD, and infliximab (IFX) was appropriate when these had previously failed or had not been tolerated. In patients with a prior successful treatment by IFX, this drug, with or without co-administration of a thiopurine analog, was favoured. Other anti-TNFs were ava i l a b l e a t w w w. s c i e n c e d i r e c t . c o m Journal of Crohn's and Colitis (2009) 3, 232-240 appropriate in the presence of intolerance or resistance to IFX. High-dose steroids, IFX or adalimumab were appropriate in severe active CD. For the 105 indications for ST-D or ST-R disease, the panel considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for limited resection, to be appropriate, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. Conclusion: Steroids, including budesonide for mild-to-moderate CD, remain the first-line therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the amount of available evidence, remain the second-line therapy for most indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D patients and ST-R patients.
Gastroenterology, 2009
self-applied adhesion declaration and self-medication. An activity index was calculated on the sp... more self-applied adhesion declaration and self-medication. An activity index was calculated on the spot (Harvey-Bradshaw/Truelove) Results: Mean age was 41.3±11 years, 60% were women. The number of years since IBD diagnosis was 8±7; 64% were Crohn's disease (71% inactive), 36% ulcerative colitis (70% inactive). A 66% was treated with aminosalicylates, 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBD-related surgical procedure. A 69% (95%CI: 60-77%) showed some type of non-adhesion. A 66% (57-75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (9-22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (17-33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95%CI 1.1-8.4; p= 0.03) and feeling little informed about their disease (OR 4.9; 95%CI 1.1-23.8; p=0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95%CI 0.11-0.74; p=0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion W1221 AIM: Azathioprine (AZA) is frequently used in inflammatory bowel disease (IBD) for inducing and maintaining remission, sparing the use of steroids. The treatment must be withdrawn in 15% of patients due to the occurrence of adverse events, often related to the genetic background of the patients. Side effects are dose-independent (allergic reactions, idiosyncrasies) or dose-dependent (myelotoxicity, hepatitis, cancer). Aim of this study has been to investigate the prevalence of adverse effects, type and time of onset of AZA in a large series of Italian IBD patients, from a single centre. MATERIALS AND METHODS: Two thousand and fourteen consecutive IBD out-patients, referred to our Institution, were retrospectively studied. AZA was prescribed to 297 patients, 137 (46.1%) affected by ulcerative colitis (UC) and 160 (53.9%) by Crohn's disease (CD). One hundred and sixty-one (54.2%) were male and 136 (45.8%) female (average age of 32.38 +/-13.33 SD years, range 10-75 y.). RESULTS: Seventy-seven patients (26%) discontinued the treatment due to side effects, 39 with UC, and 38 with CD, with a respective prevalence of 28.5 % and 23,7%. The side effects was classified as dose independent 14.6% and dose dependent 13.9% in UC patients (one patient died due to severe leucopenia) and dose independent 10% and 13.7% dose dependent in CD patients. Side effects were observed after a mean period of 14.5 +/-20.3 SD months (range 0.5-123 m.). One hundred and fifty-three patients (51.5%) are still under treatment with AZA. The dose was reduced in 20 patients (13.1%) following the occurrence of mild side effects (3.9% dose independent and 9.2% dose dependent), 133 (86.9%) are still under treatment at full dosage. Thirty-six patients (12.1%) stopped therapy after obtaining stable remission, while 24 (8.1%), due to treatment failure. CONCLUSIONS: The prevalence of side effects leading to the withdrawal of AZA treatment was higher (26%) than that usually reported (15%). This higher prevalence may be attributed to genetic factors (prevalence of the phenotypic expression of the TPMT gene or other enzymes involved in AZA metabolism). The differing cut-off levels of leucocyte/lymphocyte considered at risk and leading to the suspension of treatment or reduction of dosage may also be responsible for discordance. Eleven percent of patients showed dose dependent effects 12 months from the onset of therapy, casting doubt on the adherence to the treatment schedule, at least in a subset of patients. Nonetheless this observation prompts prolonging clinical and biochemical controls over the usual six-month period.
self-applied adhesion declaration and self-medication. An activity index was calculated on the sp... more self-applied adhesion declaration and self-medication. An activity index was calculated on the spot (Harvey-Bradshaw/Truelove) Results: Mean age was 41.3±11 years, 60% were women. The number of years since IBD diagnosis was 8±7; 64% were Crohn's disease (71% inactive), 36% ulcerative colitis (70% inactive). A 66% was treated with aminosalicylates, 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBD-related surgical procedure. A 69% (95%CI: 60-77%) showed some type of non-adhesion. A 66% (57-75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (9-22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (17-33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95%CI 1.1-8.4; p= 0.03) and feeling little informed about their disease (OR 4.9; 95%CI 1.1-23.8; p=0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95%CI 0.11-0.74; p=0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion W1221 AIM: Azathioprine (AZA) is frequently used in inflammatory bowel disease (IBD) for inducing and maintaining remission, sparing the use of steroids. The treatment must be withdrawn in 15% of patients due to the occurrence of adverse events, often related to the genetic background of the patients. Side effects are dose-independent (allergic reactions, idiosyncrasies) or dose-dependent (myelotoxicity, hepatitis, cancer). Aim of this study has been to investigate the prevalence of adverse effects, type and time of onset of AZA in a large series of Italian IBD patients, from a single centre. MATERIALS AND METHODS: Two thousand and fourteen consecutive IBD out-patients, referred to our Institution, were retrospectively studied. AZA was prescribed to 297 patients, 137 (46.1%) affected by ulcerative colitis (UC) and 160 (53.9%) by Crohn's disease (CD). One hundred and sixty-one (54.2%) were male and 136 (45.8%) female (average age of 32.38 +/-13.33 SD years, range 10-75 y.). RESULTS: Seventy-seven patients (26%) discontinued the treatment due to side effects, 39 with UC, and 38 with CD, with a respective prevalence of 28.5 % and 23,7%. The side effects was classified as dose independent 14.6% and dose dependent 13.9% in UC patients (one patient died due to severe leucopenia) and dose independent 10% and 13.7% dose dependent in CD patients. Side effects were observed after a mean period of 14.5 +/-20.3 SD months (range 0.5-123 m.). One hundred and fifty-three patients (51.5%) are still under treatment with AZA. The dose was reduced in 20 patients (13.1%) following the occurrence of mild side effects (3.9% dose independent and 9.2% dose dependent), 133 (86.9%) are still under treatment at full dosage. Thirty-six patients (12.1%) stopped therapy after obtaining stable remission, while 24 (8.1%), due to treatment failure. CONCLUSIONS: The prevalence of side effects leading to the withdrawal of AZA treatment was higher (26%) than that usually reported (15%). This higher prevalence may be attributed to genetic factors (prevalence of the phenotypic expression of the TPMT gene or other enzymes involved in AZA metabolism). The differing cut-off levels of leucocyte/lymphocyte considered at risk and leading to the suspension of treatment or reduction of dosage may also be responsible for discordance. Eleven percent of patients showed dose dependent effects 12 months from the onset of therapy, casting doubt on the adherence to the treatment schedule, at least in a subset of patients. Nonetheless this observation prompts prolonging clinical and biochemical controls over the usual six-month period.
Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimm... more Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimmunity. The gastro-intestinal tract (GIT) is frequently involved with any segment being potentially affected from mouth to anus. The esophagus is the most common localization resulting in reflux and its complications such as erosive esophagitis and Barrett's esophagus. Gastric involvement is less frequent but may be complicated by hemorrhage due to gastric antral vascular ectasia (GAVE or watermelon stomach). Intestinal involvement may lead to malabsorption, intestinal pseudo-obstruction or bacterial overgrowth. Anorectal involvement can cause fecal incontinence and rectal prolapse. GIT involvement greatly affects morbimortality in SSc and therapeutic approaches essentially aim at relieving the symptoms
Systemic sclerosis (SSc) is a protean disorder in which prognosis and treatment are tailored on t... more Systemic sclerosis (SSc) is a protean disorder in which prognosis and treatment are tailored on the basis of organ involvement. Among SSc lung manifestations, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) or the combination of both, are the first cause of SSc mortality and impact heavily on patient quality of life. ILD may begin early in disease and usually progresses slowly. However, approximately 10% of patients with ILD may reach terminal respiratory insufficiency. PAH may be an early or late complication of SSc in which increased blood pressure in pulmonary arteries leads to right heart failure. Current treatments provide some benefit, but both SSc-ILD and PAH still represent an enormous unmet need of more efficacious therapeutic strategies
Revue médicale suisse, Jan 16, 2014
Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimm... more Systemic sclerosis (SSc) is a rare disorder associating vasculopathy, tissue fibrosis and autoimmunity. The gastro-intestinal tract (GIT) is frequently involved with any segment being potentially affected from mouth to anus. The esophagus is the most common localization resulting in reflux and its complications such as erosive esophagitis and Barrett's esophagus. Gastric involvement is less frequent but may be complicated by hemorrhage due to gastric antral vascular ectasia (GAVE or watermelon stomach). Intestinal involvement may lead to malabsorption, intestinal pseudo-obstruction or bacterial overgrowth. Anorectal involvement can cause fecal incontinence and rectal prolapse. GIT involvement greatly affects morbimortality in SSc and therapeutic approaches essentially aim at relieving the symptoms.
La gazette médicale - info@gériatrie, 2018
Les réactions alimentaires indésirables sont une plainte fréquente dans la population générale. S... more Les réactions alimentaires indésirables sont une plainte fréquente dans la population générale. Selon les études épidémiologiques, environ 20% à 30% des personnes interrogées rapportent en souffrir. Ces réactions peuvent être classifiées selon leur mécanisme, soit immunologique (allergie alimentaire), non-immunologique (intolérance alimentaire) ou toxique. Bien qu’il n’y ait pas de données précises, les intolérances alimentaires seraient en augmentation, phénomène probablement amplifié par une forte couverture médiatique. Cet article a pour but d’énoncer les principales réactions alimentaires chez l’adulte, de discuter de la procédure diagnostique et des traitement
self-applied adhesion declaration and self-medication. An activity index was calculated on the sp... more self-applied adhesion declaration and self-medication. An activity index was calculated on the spot (Harvey-Bradshaw/Truelove) Results: Mean age was 41.3±11 years, 60% were women. The number of years since IBD diagnosis was 8±7; 64% were Crohn's disease (71% inactive), 36% ulcerative colitis (70% inactive). A 66% was treated with aminosalicylates, 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBD-related surgical procedure. A 69% (95%CI: 60-77%) showed some type of non-adhesion. A 66% (57-75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (9-22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (17-33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95%CI 1.1-8.4; p= 0.03) and feeling little informed about their disease (OR 4.9; 95%CI 1.1-23.8; p=0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95%CI 0.11-0.74; p=0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion W1221 AIM: Azathioprine (AZA) is frequently used in inflammatory bowel disease (IBD) for inducing and maintaining remission, sparing the use of steroids. The treatment must be withdrawn in 15% of patients due to the occurrence of adverse events, often related to the genetic background of the patients. Side effects are dose-independent (allergic reactions, idiosyncrasies) or dose-dependent (myelotoxicity, hepatitis, cancer). Aim of this study has been to investigate the prevalence of adverse effects, type and time of onset of AZA in a large series of Italian IBD patients, from a single centre. MATERIALS AND METHODS: Two thousand and fourteen consecutive IBD out-patients, referred to our Institution, were retrospectively studied. AZA was prescribed to 297 patients, 137 (46.1%) affected by ulcerative colitis (UC) and 160 (53.9%) by Crohn's disease (CD). One hundred and sixty-one (54.2%) were male and 136 (45.8%) female (average age of 32.38 +/-13.33 SD years, range 10-75 y.). RESULTS: Seventy-seven patients (26%) discontinued the treatment due to side effects, 39 with UC, and 38 with CD, with a respective prevalence of 28.5 % and 23,7%. The side effects was classified as dose independent 14.6% and dose dependent 13.9% in UC patients (one patient died due to severe leucopenia) and dose independent 10% and 13.7% dose dependent in CD patients. Side effects were observed after a mean period of 14.5 +/-20.3 SD months (range 0.5-123 m.). One hundred and fifty-three patients (51.5%) are still under treatment with AZA. The dose was reduced in 20 patients (13.1%) following the occurrence of mild side effects (3.9% dose independent and 9.2% dose dependent), 133 (86.9%) are still under treatment at full dosage. Thirty-six patients (12.1%) stopped therapy after obtaining stable remission, while 24 (8.1%), due to treatment failure. CONCLUSIONS: The prevalence of side effects leading to the withdrawal of AZA treatment was higher (26%) than that usually reported (15%). This higher prevalence may be attributed to genetic factors (prevalence of the phenotypic expression of the TPMT gene or other enzymes involved in AZA metabolism). The differing cut-off levels of leucocyte/lymphocyte considered at risk and leading to the suspension of treatment or reduction of dosage may also be responsible for discordance. Eleven percent of patients showed dose dependent effects 12 months from the onset of therapy, casting doubt on the adherence to the treatment schedule, at least in a subset of patients. Nonetheless this observation prompts prolonging clinical and biochemical controls over the usual six-month period.
Journal of Crohn's and Colitis, 2009
The increasing number of trials testing management strategies for luminal Crohn's disease (CD) ha... more The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not filled all the gaps in our knowledge and thus, in clinical practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence. Methods: A multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroiddependent (ST-D) and steroid-refractory (ST-R) CD. Results: Overall, 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated. In anti-TNF naïve patients, budesonide and prednisone were found to be appropriate for mild-moderate CD, and infliximab (IFX) was appropriate when these had previously failed or had not been tolerated. In patients with a prior successful treatment by IFX, this drug, with or without co-administration of a thiopurine analog, was favoured. Other anti-TNFs were ava i l a b l e a t w w w. s c i e n c e d i r e c t . c o m Journal of Crohn's and Colitis (2009) 3, 232-240 appropriate in the presence of intolerance or resistance to IFX. High-dose steroids, IFX or adalimumab were appropriate in severe active CD. For the 105 indications for ST-D or ST-R disease, the panel considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for limited resection, to be appropriate, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. Conclusion: Steroids, including budesonide for mild-to-moderate CD, remain the first-line therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the amount of available evidence, remain the second-line therapy for most indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D patients and ST-R patients.
Gastroenterology, 2009
self-applied adhesion declaration and self-medication. An activity index was calculated on the sp... more self-applied adhesion declaration and self-medication. An activity index was calculated on the spot (Harvey-Bradshaw/Truelove) Results: Mean age was 41.3±11 years, 60% were women. The number of years since IBD diagnosis was 8±7; 64% were Crohn's disease (71% inactive), 36% ulcerative colitis (70% inactive). A 66% was treated with aminosalicylates, 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBD-related surgical procedure. A 69% (95%CI: 60-77%) showed some type of non-adhesion. A 66% (57-75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (9-22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (17-33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95%CI 1.1-8.4; p= 0.03) and feeling little informed about their disease (OR 4.9; 95%CI 1.1-23.8; p=0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95%CI 0.11-0.74; p=0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion W1221 AIM: Azathioprine (AZA) is frequently used in inflammatory bowel disease (IBD) for inducing and maintaining remission, sparing the use of steroids. The treatment must be withdrawn in 15% of patients due to the occurrence of adverse events, often related to the genetic background of the patients. Side effects are dose-independent (allergic reactions, idiosyncrasies) or dose-dependent (myelotoxicity, hepatitis, cancer). Aim of this study has been to investigate the prevalence of adverse effects, type and time of onset of AZA in a large series of Italian IBD patients, from a single centre. MATERIALS AND METHODS: Two thousand and fourteen consecutive IBD out-patients, referred to our Institution, were retrospectively studied. AZA was prescribed to 297 patients, 137 (46.1%) affected by ulcerative colitis (UC) and 160 (53.9%) by Crohn's disease (CD). One hundred and sixty-one (54.2%) were male and 136 (45.8%) female (average age of 32.38 +/-13.33 SD years, range 10-75 y.). RESULTS: Seventy-seven patients (26%) discontinued the treatment due to side effects, 39 with UC, and 38 with CD, with a respective prevalence of 28.5 % and 23,7%. The side effects was classified as dose independent 14.6% and dose dependent 13.9% in UC patients (one patient died due to severe leucopenia) and dose independent 10% and 13.7% dose dependent in CD patients. Side effects were observed after a mean period of 14.5 +/-20.3 SD months (range 0.5-123 m.). One hundred and fifty-three patients (51.5%) are still under treatment with AZA. The dose was reduced in 20 patients (13.1%) following the occurrence of mild side effects (3.9% dose independent and 9.2% dose dependent), 133 (86.9%) are still under treatment at full dosage. Thirty-six patients (12.1%) stopped therapy after obtaining stable remission, while 24 (8.1%), due to treatment failure. CONCLUSIONS: The prevalence of side effects leading to the withdrawal of AZA treatment was higher (26%) than that usually reported (15%). This higher prevalence may be attributed to genetic factors (prevalence of the phenotypic expression of the TPMT gene or other enzymes involved in AZA metabolism). The differing cut-off levels of leucocyte/lymphocyte considered at risk and leading to the suspension of treatment or reduction of dosage may also be responsible for discordance. Eleven percent of patients showed dose dependent effects 12 months from the onset of therapy, casting doubt on the adherence to the treatment schedule, at least in a subset of patients. Nonetheless this observation prompts prolonging clinical and biochemical controls over the usual six-month period.
self-applied adhesion declaration and self-medication. An activity index was calculated on the sp... more self-applied adhesion declaration and self-medication. An activity index was calculated on the spot (Harvey-Bradshaw/Truelove) Results: Mean age was 41.3±11 years, 60% were women. The number of years since IBD diagnosis was 8±7; 64% were Crohn's disease (71% inactive), 36% ulcerative colitis (70% inactive). A 66% was treated with aminosalicylates, 51% with immunosuppressors, 8% with glucocorticoids. A 66% needed an IBD-related hospital admission in the past, and 17% any IBD-related surgical procedure. A 69% (95%CI: 60-77%) showed some type of non-adhesion. A 66% (57-75%) acknowledged dome degree of involuntary non-adhesion: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (9-22%) showed some kind of voluntary non-adhesion: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% (17-33%) forgot at least a dose a week (mean weekly number of forgotten doses 1.6), and the most frequent cause was to be away form home when they were supposed to take the medication. This was more frequent under mesalazine therapy (30%) than with azathioprine (17%) (p=n.s.). A multivariate analysis identified as risk factors for a lower adhesion the dosing in three or more takes a day (OR 3; 95%CI 1.1-8.4; p= 0.03) and feeling little informed about their disease (OR 4.9; 95%CI 1.1-23.8; p=0.04). On the other hand, immunomodulator therapy was a predictive factor for better adhesion (OR 0.29; 95%CI 0.11-0.74; p=0.01). The concordance between patient recall and clinical records was complete in 86%, whereas in 10.3% the patients did not accurately remember the dose and in 3.7% there was confusion about the drug taken. A 9% acknowledged self-medication during flares Conclusions: In our setting, adhesion to therapy in IBD patients is not satisfactory. Patients treated with immunosuppressors have better adhesion. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adhesion W1221 AIM: Azathioprine (AZA) is frequently used in inflammatory bowel disease (IBD) for inducing and maintaining remission, sparing the use of steroids. The treatment must be withdrawn in 15% of patients due to the occurrence of adverse events, often related to the genetic background of the patients. Side effects are dose-independent (allergic reactions, idiosyncrasies) or dose-dependent (myelotoxicity, hepatitis, cancer). Aim of this study has been to investigate the prevalence of adverse effects, type and time of onset of AZA in a large series of Italian IBD patients, from a single centre. MATERIALS AND METHODS: Two thousand and fourteen consecutive IBD out-patients, referred to our Institution, were retrospectively studied. AZA was prescribed to 297 patients, 137 (46.1%) affected by ulcerative colitis (UC) and 160 (53.9%) by Crohn's disease (CD). One hundred and sixty-one (54.2%) were male and 136 (45.8%) female (average age of 32.38 +/-13.33 SD years, range 10-75 y.). RESULTS: Seventy-seven patients (26%) discontinued the treatment due to side effects, 39 with UC, and 38 with CD, with a respective prevalence of 28.5 % and 23,7%. The side effects was classified as dose independent 14.6% and dose dependent 13.9% in UC patients (one patient died due to severe leucopenia) and dose independent 10% and 13.7% dose dependent in CD patients. Side effects were observed after a mean period of 14.5 +/-20.3 SD months (range 0.5-123 m.). One hundred and fifty-three patients (51.5%) are still under treatment with AZA. The dose was reduced in 20 patients (13.1%) following the occurrence of mild side effects (3.9% dose independent and 9.2% dose dependent), 133 (86.9%) are still under treatment at full dosage. Thirty-six patients (12.1%) stopped therapy after obtaining stable remission, while 24 (8.1%), due to treatment failure. CONCLUSIONS: The prevalence of side effects leading to the withdrawal of AZA treatment was higher (26%) than that usually reported (15%). This higher prevalence may be attributed to genetic factors (prevalence of the phenotypic expression of the TPMT gene or other enzymes involved in AZA metabolism). The differing cut-off levels of leucocyte/lymphocyte considered at risk and leading to the suspension of treatment or reduction of dosage may also be responsible for discordance. Eleven percent of patients showed dose dependent effects 12 months from the onset of therapy, casting doubt on the adherence to the treatment schedule, at least in a subset of patients. Nonetheless this observation prompts prolonging clinical and biochemical controls over the usual six-month period.