Efficacy and safety of lubiprostone for the treatment of chronic idiopathic constipation: A phase 3, randomized, placebo-controlled study.

INTRODUCTION: Chronic idiopathic constipation (CIC) negatively impacts quality of life and increases healthcare costs. Lubiprostone stimulates the secretion of intestinal fluid, in turn facilitating the passage of stools and alleviating associated symptoms. Lubiprostone has been available in Mexico since 2018, but its clinical efficacy has not been studied in a Mexican population. AIM: To evaluate the efficacy of lubiprostone, assessed by changes in spontaneous bowel movement (SBM) frequency after one week of treatment with 24 µg oral lubiprostone (b.i.d.), as well as its safety, over four weeks of treatment. STUDY: Randomized, double-blind, placebo-controlled study on 211 adults with CIC in Mexico. RESULTS: The increase in SBM frequency, after one week of treatment, was significantly higher in the lubiprostone group than in the placebo group (mean: 4.9 [SD: 4.45] vs. 3.0 [3.14], p = 0.020). Secondary efficacy endpoints revealed a significantly higher proportion of SBM frequency/week in the lubiprostone group at weeks 2, 3, and 4. There was a better response within 24 h after the first dose with lubiprostone vs. placebo (60.0% vs. 41.5%; OR: 2.08, CI95%: [1.19, 3.62], p = 0.009) and the lubiprostone group also had significant improvement, with respect to straining, stool consistency, abdominal bloating, and Satisfaction Index. The main adverse events were gastrointestinal disorders in 13 (12.4%) lubiprostone-treated subjects and 4 (3.8%) control subjects. CONCLUSIONS: Our data confirm the efficacy and safety of lubiprostone for the treatment of CIC in a Mexican population. Lubiprostone treatment induces relief from the most bothersome symptoms associated with constipation.

Systematic review with meta-analysis: lubiprostone efficacy on the treatment of patients with constipation / Revisão sistemática com metanálise: eficácia da lubiprostona no tratamento de pacientes com constipação

ABSTRACT BACKGROUND: Lubiprostone is a type 2 chloride channel activator that has been shown to be efficacious and safe in the treatment for chronic constipation. OBJECTIVE: To systematically review randomized clinical trials (RCTs) assessing efficacy of lubiprostone for patients with chronic idiopathic constipation (CIC), irritable bowel syndrome with predominant constipation (IBS-C) and opioid-induced constipation (OIC). METHODS: Searches were conducted in PubMed, LILACS, Cochrane Collaboration Database, and Centre for Reviews and Dissemination. Lubiprostone RCTs reporting outcomes of spontaneous bowel movements (SBM) and abdominal pain or discomfort were deemed eligible. Meta-analysis was performed calculating risk ratios and 95% confidence intervals, using the Mantel-Haenszel method and random effects model. RESULTS: Searches yielded 109 records representing 93 non-duplicate publications, and 11 RCTs (978 CIC, 1,366 IBS-C, 1,300 OIC, total = 3,644) met inclusion criteria. Qualitative synthesis showed that for CIC patients, lubiprostone is superior to placebo in terms of SBM outcomes. Meta-analysis for CIC was feasible for full responder and SBM within 24h rates, indicating superiority of lubiprostone over placebo. For IBS-C, lubiprostone was significantly superior for all SBM outcomes in follow-ups ranging from 1 week-3 months. In terms of abdominal pain, lubiprostone provided significantly better symptoms relief, particularly after 1 month of treatment. For OIC, lubiprostone was more effective than placebo for both SBM and discomfort measures. CONCLUSION: Our findings demonstrated that lubiprostone is superior to placebo in terms of SBM frequency for CIC, IBS-C and OIC. In terms of abdominal symptoms, the most pronounced effect was seen for abdominal pain in IBS-C patients.

RESUMO CONTEXTO: Lubiprostona é um ativador de canal de cloreto tipo 2 que tem se demonstrado eficaz e seguro no tratamento da constipação crônica. OBJETIVO: Revisar sistematicamente ensaios clínicos randomizados (ECRs) avaliando a eficácia da lubiprostona para pacientes com constipação idiopática crônica (CIC), síndrome do intestino irritável com constipação predominante (IBS-C) e constipação induzida por opioide (OIC). MÉTODOS: Buscas foram conduzidas no PubMed, LILACS, Cochrane Collaboration Database e Centre for Reviews and Dissemination. ECRs de lubiprostona relatando desfechos de movimentos intestinais espontâneos (SBM) e dor ou desconforto abdominal foram considerados elegíveis. Metanálise foi realizada calculando razão de riscos e intervalos de confiança de 95%, utilizando o método de Mantel-Haenszel e modelo de efeitos aleatórios. RESULTADOS: As buscas identificaram 109 registros representando 93 publicações não-duplicadas e 11 ECRs (978 pacientes de CIC, 1366 de IBS-C e 1300 OIC, total = 3644) preencheram os critérios de inclusão. Síntese qualitativa mostrou que, para pacientes com CIC, a lubiprostona foi superior ao placebo em termos de desfechos SBM. Metanálise para CIC foi possível para os desfechos de responder completo e taxa de SBM em 24 horas, indicando superioridade da lubiprostona sobre o placebo. Para IBS-C, lubiprostona foi significativamente superior para todos os desfechos de SBM em tempos de seguimento variando de 1 semana a 3 meses. Em termos de dor abdominal, lubiprostona proporciono alívio dos sintomas significativamente melhor, particularmente após 1 mês de tratamento. Para OIC, lubiprostona foi mais efetiva do que placebo tanto para medidas de SBM quando de desconforto abdominal. CONCLUSÃO: Nossos achados demonstraram que lubiprostona é superior ao placebo em termos de frequência de SBM para CIC, IBS-C e OIC. Em termos de sintomas abdominais, o efeito mais pronunciado foi visto para dor abdominal em pacientes com IBS-C.