RESUMO
BACKGROUND: Data about the safety of allopurinol in pregnant women are sparsely reported. AIMS: To investigate the risk of adverse pregnancy outcome and congenital abnormalities after in utero exposure to allopurinol in inflammatory bowel disease (IBD) pregnancies and in general. METHODS: We collected safety data of patients with IBD who were treated with allopurinol during pregnancy between January 2013 and March 2022. Additionally, we performed a systematic review about the teratogenic potential of allopurinol. RESULTS: We collected data from 42 allopurinol-exposed pregnancies, including one twin pregnancy; in all women, allopurinol was combined with a thiopurine. Six pregnancies (14.3%) resulted in miscarriage and one in stillbirth at 32 weeks. A congenital anomaly was observed in one newborn (coarctation of the aorta discovered postpartum). Three pregnancies, including the twin pregnancy, ended in moderate preterm delivery and one in very preterm delivery. Five neonates (15.2%) were small for gestational age. From our literature search, we identified an additional 102 allopurinol-exposed pregnancies resulting in 129 live births, including 36 infants from our cohort. Ten infants (7.8%) were born with a congenital anomaly. Two (1.6%) had a comparable pattern of multiple anomalies. The systematic review sub-analysis including only infants born to mothers with IBD (n = 76) revealed that 2.6% of infants had congenital anomalies after in utero exposure to a low dose of allopurinol. CONCLUSIONS: Overall, the teratogenicity of allopurinol remains inconclusive. Children conceived by mothers treated for IBD with allopurinol/thiopurine co-therapy do not seem to have an increased risk of congenital anomalies.
Assuntos
Anormalidades Induzidas por Medicamentos , Alopurinol , Doenças Inflamatórias Intestinais , Complicações na Gravidez , Resultado da Gravidez , Humanos , Gravidez , Alopurinol/efeitos adversos , Feminino , Complicações na Gravidez/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Recém-Nascido , Adulto , Anormalidades Induzidas por Medicamentos/etiologiaRESUMO
Drug rediscovery refers to the principle of using 'old' drugs outside the indications mentioned in the summary of product characteristics. In the past decades, several drugs were rediscovered in a wide variety of medical fields. One of the most recent examples is the unconditional registration of thioguanine (TG), a thiopurine derivative, in patients with inflammatory bowel disease in the Netherlands. In this paper, we aim to visualise potential hurdles that hamper drug rediscovery in general, emphasise the global need for optimal use and development of potentially useful drugs, and provide an overview of the registration process for TG in the Netherlands. With this summary, we aim to guide drug rediscovery trajectories in the near future.
Assuntos
Gastroenterologia , Doenças Inflamatórias Intestinais , Humanos , Tioguanina/uso terapêutico , Uso Off-Label , Doenças Inflamatórias Intestinais/tratamento farmacológico , Países Baixos , Azatioprina/uso terapêutico , Mercaptopurina/uso terapêutico , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Thioguanine is a well-tolerated and effective therapy for inflammatory bowel disease [IBD] patients. Prospective effectiveness data are needed to substantiate the role of thioguanine as a maintenance therapy for IBD. METHODS: IBD patients who previously failed azathioprine or mercaptopurine and initiated thioguanine were prospectively followed for 12 months starting when corticosteroid-free clinical remission was achieved (Harvey-Bradshaw Index [HBI] ≤ 4 or Simple Clinical Colitis Activity Index [SCCAI] ≤ 2). The primary endpoint was corticosteroid-free clinical remission throughout 12 months. Loss of clinical remission was defined as SCCAI > 2 or HBI > 4, need of surgery, escalation of therapy, initiation of corticosteroids or study discontinuation. Additional endpoints were adverse events, drug survival, physician global assessment [PGA] and quality of life [QoL]. RESULTS: Sustained corticosteroid-free clinical remission at 3, 6 or 12 months was observed in 75 [69%], 66 [61%] and 49 [45%] of 108 patients, respectively. Thioguanine was continued in 86 patients [80%] for at least 12 months. Loss of response [55%] included escalation to biologicals in 15%, corticosteroids in 10% and surgery in 3%. According to PGA scores, 82% of patients were still in remission after 12 months and QoL scores remained stable. Adverse events leading to discontinuation were reported in 11%, infections in 10%, myelo- and hepatotoxicity each in 6%, and portal hypertension in 1% of patients. CONCLUSION: Sustained corticosteroid-free clinical remission over 12 months was achieved in 45% of IBD patients on monotherapy with thioguanine. A drug continuation rate of 80%, together with favourable PGA and QoL scores, underlines the tolerability and effectiveness of thioguanine for IBD.
Assuntos
Colite , Doenças Inflamatórias Intestinais , Humanos , Tioguanina/uso terapêutico , Qualidade de Vida , Estudos Prospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Azatioprina/uso terapêutico , Mercaptopurina/uso terapêutico , Colite/induzido quimicamente , Imunossupressores/efeitos adversosRESUMO
BACKGROUND: Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. METHODS: In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. RESULTS: Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn's disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [nâ =â 17] and 7% [nâ =â 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. CONCLUSION: In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.
Assuntos
Aborto Espontâneo , Doenças Inflamatórias Intestinais , Complicações na Gravidez , Gravidez , Recém-Nascido , Criança , Humanos , Feminino , Adulto , Tioguanina/efeitos adversos , Resultado da Gravidez/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Natimorto/epidemiologia , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologiaRESUMO
BACKGROUND: Approximately 25% of patients with inflammatory bowel disease (IBD) discontinue azathioprine (AZA) or mercaptopurine (MP) therapy within 3 months of treatment initiation because of adverse drug reactions. Of these side-effects, about half are because of hepatotoxicity. The aim of this study was to validate and (subsequently) optimize a previously reported predictive algorithm for thiopurine-associated hepatotoxicity by increasing the number of patients with IBD benefitting from conventional thiopurine therapy. METHODS: This multicenter observational study included consecutive thiopurine-naive patients with IBD who received AZA or MP treatment. The primary outcome was hepatotoxicity within 12 weeks. The patients with and without hepatotoxicity were compared. Four determinants, namely, age, sex, body mass index (BMI), and 6-methylmercaptopurine ribonucleotide concentrations 1 week after treatment initiation (T = 1) were used to validate and optimize 2 (1 dichotomous and 1 continuous) algorithms using multivariable logistic regression analysis. RESULTS: Of 229 patients, 21 (9%) developed hepatotoxicity and 93% of the patients received MP with a median dose of 0.7 mg/kg (95% confidence interval 0.3-1.4 mg/kg). A difference in BMI was found between with and without hepatotoxicity groups (median 27.6 versus 24.2, P = 0.022). Specificities of 68% (Algorithm 1) and 77% (Algorithm 2) and sensitivities of 56% (Algorithm 1) and 50% (Algorithm 2) were obtained. CONCLUSIONS: Both algorithms demonstrated limited predictive accuracy for thiopurine-induced hepatotoxicity in the validation cohort. Relevant factors contributing to this outcome were changes in thiopurine prescription behavior over time, with more MP prescriptions at relatively lower dosages of MP.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Inflamatórias Intestinais , Humanos , Mercaptopurina/efeitos adversos , Azatioprina/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Algoritmos , Imunossupressores/efeitos adversosRESUMO
Thiopurine-derivates azathioprine and mercaptopurine are frequently used to maintain remission in inflammatory bowel diseases (IBD). Despite their efficacy, more than 50% of patients discontinue therapy, mainly due to the development of adverse events. Thioguanine is an alternative thiopurine and has been conditionally licensed in The Netherlands as IBD treatment for patients after conventional thiopurine therapy failure. In this review we will provide practical information on initiating and maintaining thioguanine therapy in IBD and provide information concerning safety issues and future perspectives. The thioguanine toxicity profile is relatively mild and the reported incidence of nodular regenerative hyperplasia related to thioguanine use seems comparable to conventional thiopurines and the background incidence in IBD patients. Routine monitoring of laboratory parameters and adverse events is recommended, comparable to the monitoring of patients on conventional thiopurine therapy.
Assuntos
Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Tioguanina/uso terapêutico , HumanosRESUMO
BACKGROUND: Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP. METHODS: A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected. RESULTS: A total of 193 patients (57% female and 64% Crohn's disease) were included, with a median daily TG dose of 20 mg (range: 20-40 mg), a median treatment duration of 23 months (IQR 10-47) and a median follow-up of 36 months (IQR 22-53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 105 RBC (IQR 145-1761) and 47 mu/L (IQR 34.5-96). CONCLUSIONS: Long-term follow-up suggests that TG can be an effective and well-tolerated therapy in more than half of difficult-to-treat and multi-therapy failing IBD patients. Findings of this study indicate that TG can be used safely and the occurrence of hepatotoxicity was low. The incidence rate of NRH was within the background incidence.
Assuntos
Doenças Inflamatórias Intestinais , Preparações Farmacêuticas , Azatioprina/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Mercaptopurina , Estudos Retrospectivos , Tioguanina/efeitos adversos , Resultado do Tratamento , Reino UnidoRESUMO
BACKGROUND: Both tioguanine and low-dose thiopurines combined with allopurinol (LDTA) can be considered for the treatment of inflammatory bowel disease (IBD) when conventional thiopurines fail due to adverse events. AIM: To compare the safety of tioguanine and LDTA in IBD patients. METHODS: Inflammatory bowel disease patients who failed conventional thiopurines due to adverse events and initiated LDTA in standard care were identified in the prospective ICC Registry. IBD patients who failed conventional thiopurines due to adverse events and initiated tioguanine were enrolled in three university hospitals. Patients on concomitant biologicals were excluded. The primary outcome was discontinuation of therapy due to adverse events. Secondary outcomes included: safety outcomes and surgery-, biological- and corticosteroid-free clinical remission (physician global assessment = 0) after 104 weeks. Both multiple logistic regression and propensity score matching were used to correct for confounders. RESULTS: In total, 182 IBD patients treated with tioguanine (n = 94) or LDTA (n = 88) were included with a median follow-up of 104 weeks (IQR 91-104). Of these, 19% (tioguanine: 20%, LDTA: 18%) of patients discontinued therapy due to adverse events. After adjusting for confounders, there were no differences in terms of discontinuation rate due to adverse events (OR 0.50, 95% CI 0.15-1.68, P = 0.26), adverse events (OR 0.89, 95% CI 0.44-1.81, P = 0.75), infections (OR 1.05, 95% CI 0.40-2.73, P = 0.93), hospitalisations (OR 2.00, 95% CI 0.64-6.23, P = 0.23) or clinical remission (OR 0.74, 95%CI 0.33-1.68, P = 0.48). All results are comparable with the propensity score matched cohort. CONCLUSION: Nineteen percent of IBD patients with prior failure to conventional thiopurines due to adverse events discontinued therapy with tioguanine or LDTA due to adverse events. Either therapy may be considered before escalating to biological therapy.
Assuntos
Alopurinol/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Purinas/administração & dosagem , Tioguanina/administração & dosagem , Adulto , Alopurinol/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Purinas/efeitos adversos , Sistema de Registros , Tioguanina/efeitos adversos , Resultado do TratamentoRESUMO
Introduction: In the 1950s, thioguanine (TG), a thiopurine-derivative together with azathioprine (AZA) and mercaptopurine (MP), were developed for the treatment of childhood leukemia. Over the years, the use of TG was also explored for other, mainly immune-mediated and inflammatory, diseases such as in the field of dermatology and rheumatology (e.g. psoriasis, systemic lupus erythematosus (SLE)) and gastroenterology and hepatology (e.g. inflammatory bowel diseases (IBD), autoimmune hepatitis).Areas covered: This review provides a comprehensive overview of all the clinical uses of TG and describes its mechanism of action, pharmacokinetic/pharmacodynamic features, and toxicity.Expert opinion: Thioguanine has shown beneficial clinical effects in hematological (particularly leukemia) and several immune-inflammatory diseases including psoriasis, SLE, polycythemia vera, Churg-Strauss syndrome, IBD, collagenous sprue, refractory celiac disease, and autoimmune hepatitis. Thioguanine is not effective in treating solid-cancers. At relatively low dosages, i.e. 0.2- 0.3mg/kg/day or 20 mg/day, TG has a favorable risk-benefit ratio and is a safe and effective drug in the long-term treatment of amongst other IBD patients. Thioguanine toxicity, especially myelotoxicity, and hepatotoxicity, including nodular regenerative hyperplasia (NRH) of the liver, is limited when dosed adequately. The occurrence of NRH appears dose-dependent and has been especially described during high dose TG above 40 mg/day.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Tioguanina/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Leucemia/tratamento farmacológico , Tioguanina/efeitos adversos , Tioguanina/farmacocinéticaAssuntos
Apêndice/cirurgia , Doença de Crohn/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico , Pseudomixoma Peritoneal/diagnóstico , Adulto , Colectomia , Doença de Crohn/cirurgia , Feminino , Humanos , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Background: Thioguanine is associated with liver toxicity, especially nodular regenerative hyperplasia (NRH). We assessed if liver histology alters during long-term maintenance treatment with thioguanine in patients with inflammatory bowel disease (IBD). Methods: Liver specimens of thioguanine treated IBD patients with at least two liver biopsies were revised by two independent liver pathologists, blinded to clinical characteristics. Alterations in histopathological findings between first and sequential liver specimen were evaluated and associated clinical data, including laboratory parameters and abdominal imaging reports, were collected. Results: Twenty-five IBD patients underwent sequential liver biopsies prior to, at time of, or after cessation of thioguanine treatment. The median time between the first and second biopsy was 25 months (range: 14-54). Except for one normal liver specimen, any degree of irregularities including inflammation, steatosis, fibrosis and some vascular disturbances were observed in the biopsies. The rates of perisinusoidal fibrosis (91%), sinusoidal dilatation (68%) and nodularity (18%) were the same in the first and second liver biopsies. A trend towards statistical significance was observed for phlebosclerosis (36% of the first vs. 68% of the second biopsies, p = .092). Presence of histopathological liver abnormalities was not associated with clinical outcomes. Furthermore, two patients in this cohort had portal hypertension in presence of phlebosclerosis. In another two patients, nodularity of the liver resolved upon thioguanine withdrawal. Conclusion: Vascular abnormalities of the liver were commonly observed in thioguanine treated IBD patients, although these were not progressive and remained of limited clinical relevance over time.
Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Fígado/patologia , Tioguanina/efeitos adversos , Adulto , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Estudos de Coortes , Progressão da Doença , Feminino , Hiperplasia Nodular Focal do Fígado/induzido quimicamente , Humanos , Hipertensão Portal/induzido quimicamente , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Países Baixos , Tioguanina/administração & dosagemRESUMO
BACKGROUND: Tioguanine (or thioguanine) is an alternative drug for IBD patients who fail prior conventional immunomodulating therapy. AIM: To report effectiveness, safety and therapeutic drug monitoring in a cohort of patients with prolonged tioguanine maintenance therapy. METHODS: In this nationwide, multicentre study, medical records of tioguanine- using IBD patients were retrospectively reviewed. Response to therapy was defined as clinical effectiveness without (re)initiation of corticosteroids, concurrent biological therapy or surgical intervention. All adverse events that occurred during the follow-up were listed and graded according to the common terminology criteria (CTC). RESULTS: Two hundred and seventy-four patients (female 63%, Crohn's disease in 68%) were included with median treatment duration of 51 months, 1567 patient-years of follow-up and median 20 mg/d tioguanine dosage. Tioguanine was tolerated in 79%, clinical effectiveness at 6 months was documented in 66% and sustained clinical effectiveness during 12 months in 51% of patients. Forty-one per cent of patients developed adverse events: 5% were graded as severe. Adverse events comprised infection requiring hospitalisation in three and skin cancer in eight patients (two melanomas). Asymptomatic nodular regenerative hyperplasia of the liver occurred in two out of 52 patients with liver biopsies (3.8%) and portal hypertension in three whereof one potentially associated with tioguanine (0.4%). Clinical effectiveness was correlated with 6-thioguanine nucleotide threshold concentrations >682 pmol/8×108 RBC (P < 0.05). CONCLUSIONS: Long-term tioguanine therapy for at least 12 months was effective in 51% and well tolerated as a maintenance treatment for IBD in about 70% of patients. Adverse events were common, but mainly mild or moderate. 6-Thioguanine nucleotide threshold concentration ≥ 700 pmol/8×108 RBC is proposed as target level with higher odds for clinical effectiveness.
Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Tioguanina/uso terapêutico , Adolescente , Adulto , Anti-Inflamatórios/efeitos adversos , Monitoramento de Medicamentos , Feminino , Nucleotídeos de Guanina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tioguanina/efeitos adversos , Tionucleotídeos/sangue , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Off-label prescribing is encountered across various fields of medicine and creates alternative treatment options, but is associated with unknown safety risks. The use of off-label drugs for the treatment of patients with inflammatory bowel diseases (IBD) has not been characterised before. AIM: To assess the proportion and characteristics of off-label prescribing for IBD in tertiary care centres in the Netherlands. METHODS: A prospective database of IBD patients from all Dutch university hospitals was used to collect data on drug prescriptions for IBD and demographics. Drugs were classified as off-label if they were unlicensed for Crohn's disease and/or ulcerative colitis by the Medicines Evaluation Board. Uni- and multivariable analyses were used to identify patient-specific characteristics predictive of increased off-label use. RESULTS: For the induction and/or maintenance treatment of 4583 IBD patients, 12 651 historical and current drug records were available in the database. Of these, 2374 (19%) were considered off-label prescriptions. Out of 4583 IBD patients, 1477 (32%) were exposed to off-label drugs. Commonly prescribed off-label IBD drugs were mercaptopurine (18%), beclomethasone (12%), thioguanine (4%) and allopurinol (3%). Non-thiopurine/methotrexate off-label drugs were prescribed in 243 patients (6%), including biological agents or tofacitinib in 47 IBD patients (1%). Off-label prescriptions were more common in ulcerative colitis than Crohn's disease (37% vs 29%, P < 0.001). Smokers and patients that received ≥5 drug types during their disease course were more likely to be exposed to off-label drugs (smoking 33% vs 27% and multiple drug use 66% vs 22%, both P < 0.001). CONCLUSION: About one-fifth of prescriptions for IBD were off-label and one-third of IBD patients, especially ulcerative colitis patients, were exposed to off-label drugs.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Uso Off-Label/estatística & dados numéricos , Adolescente , Adulto , Alopurinol/uso terapêutico , Beclometasona/uso terapêutico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Países Baixos , Tioguanina/uso terapêutico , Adulto JovemRESUMO
Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).1 It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.2 The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.
Assuntos
Azatioprina/efeitos adversos , Hiperplasia/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Hepatopatias/patologia , Mercaptopurina/efeitos adversos , Tioguanina/efeitos adversos , Adolescente , Adulto , Idoso , Azatioprina/administração & dosagem , Feminino , Humanos , Hiperplasia/induzido quimicamente , Doenças Inflamatórias Intestinais/complicações , Masculino , Mercaptopurina/administração & dosagem , Pessoa de Meia-Idade , Tioguanina/administração & dosagem , Adulto JovemRESUMO
BACKGROUND AND AIM: Patient-reported outcomes and experiences are indicative of the impact and the quality of care. Thioguanine, a generic drug initially developed for leukemia, has been explored and relicensed as a certified treatment for patients with inflammatory bowel diseases (IBD). The patients' perception of this treatment has not been evaluated before. In this study, we aimed to assess self-reported experiences with thioguanine for IBD. METHODS: Questionnaires were sent out to members of the Dutch National Crohn's and Colitis patient organization. The Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) was used to address questions regarding the satisfaction and impact of thioguanine therapy on the disease and their daily life. Furthermore, data on demographics, disease and (historical) treatment characteristics were collected. Open-ended questions were used for additional comments to the questionnaire. RESULTS: A total of 173 organization members (73% female) reported to be previous or current users of thioguanine. A total of 74% were satisfied with the effectiveness of thioguanine, whereas 5% were not. Eighty percent of the respondents were satisfied with the quality of care. A good or excellent impact on daily life was reported by 54%. A neutral or bad impact on daily life was reported by 40% and 6%, respectively. Improvement of disease activity was reported by 58%. This remained stable or worsened in 39% and 3%, respectively. CONCLUSION: In this self-report survey, among thioguanine treated patients with IBD who had failed with traditional therapies, 80% reported satisfaction with medical care and 74% with the effectiveness of the therapy. In the evaluation of new or rediscovered therapies, patient-reported outcomes and experiences should be considered as a key instrument.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Aprovação de Drogas , Medicamentos Genéricos/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Tioguanina/uso terapêutico , Atividades Cotidianas , Adulto , Anti-Inflamatórios/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/psicologia , Efeitos Psicossociais da Doença , Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Doença de Crohn/psicologia , Medicamentos Genéricos/efeitos adversos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Segurança do Paciente , Indução de Remissão , Medição de Risco , Fatores de Risco , Tioguanina/efeitos adversos , Resultado do TratamentoRESUMO
Allopurinol is widely used in the management of multiple disorders including gout, kidney stones and inflammatory bowel disease. Despite of long-term experience, its safety in pregnancy has been debated due to reports on possible teratogenicity. We aimed to review the literature on the safety of allopurinol in pregnancy and offspring. In animals, allopurinol induced species-specific reproductive toxicity. In humans, a total of 53 allopurinol exposed infants were reported in the literature. Major congenital malformations were reported in two cases with a comparable pattern of multiple abnormalities. Five other infants had minor birth defects. In conclusion, the association between allopurinol and teratogenicity appears to be weak and limited to two reports with uncertain causality. However, the available data are insufficient to make a certain judgement, and as allopurinol treatment evolves, report and prospective follow-up of all exposed infants (i.e. deviant and normal cases) should be encouraged.