RESUMEN
BACKGROUND: Clinical factors were previously identified as predictors of short-term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7-year trial provides an opportunity to study predictors of short- and long-term clinical remission among CD patients treated with certolizumab pegol (CZP). AIM: To identify factors that influence long-term remission of CD with CZP treatment. METHODS: Patients who had completed placebo-controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open-label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey-Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used. RESULTS: Predictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models. CONCLUSIONS: These analyses identified several influential parameters for short-and long-term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed. (ClinicalTrials.gov identifier NCT00552058).
Asunto(s)
Certolizumab Pegol/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The efficacy and safety of certolizumab pegol (CZP) in moderate-to-severe Crohn's disease were demonstrated in two 26-week double-blind studies (PRECiSE 1 & 2). AIM: To report the safety and efficacy outcomes of long-term, CZP therapy from PRECiSE 3, in which patients received treatment up to 7 years treatment. METHODS: Patients completing PRECiSE 1 or 2 were eligible to enter PRECiSE 3 in which they received CZP 400 mg, open-label, every 4 weeks (without additional induction therapy) for up to 7 years, for up to 91 doses from study start. Safety (adverse events, including infections and malignancies) and efficacy (Harvey-Bradshaw Index, faecal calprotectin, C-reactive protein) were prospectively monitored. Remission was analysed using observed cases, last observation carried forward imputation and nonresponder imputation. RESULTS: A total of 595 patients entered the study; 117 (20%) completed 7 years. Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% (years 1-7 respectively). During 1920 patient-years of exposure to CZP, no new safety signals were observed. Incidence rates (new cases/100 patient-years) for serious infections and malignant neoplasms were 4.37 and 1.06 respectively. No lymphoproliferative malignancies were reported. Clinical remission rates were ≥68% at each year (observed cases); rates by last observation carried forward and nonresponder imputation were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7 respectively. CONCLUSION: Certolizumab pegol was well tolerated in the long-term treatment of Crohn's disease, with sustained remission in some patients continuing in the study for up to 7 years. ClinicalTrials.gov identifier NCT00552058.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inmunosupresores/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Proteína C-Reactiva/metabolismo , Certolizumab Pegol , Método Doble Ciego , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Inmunosupresores/efectos adversos , Complejo de Antígeno L1 de Leucocito/metabolismo , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Inducción de Remisión , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine predictors of sputum culture conversion among patients undergoing treatment for pulmonary tuberculosis. DESIGN: Cohort study based on data collected through the expanded tuberculosis control program in the State of North Carolina, USA. Survival analysis using Kaplan-Meier product-limit estimator and Cox proportional hazards models was employed to compute estimates for time to sputum conversion and rate ratios, respectively. RESULTS: Sputum conversion was reported in 1144 of 1735 cases (66%). Documented conversion rose significantly from 52.9% at baseline to a peak of 95.1% by the end of the study, representing a 5.1% annual increase in the proportion of patients with reported conversion (P = 0.007). Patients co-infected with the human immunodeficiency virus (HIV) had a 46% lower rate of sputum conversion than non-HIV-infected TB patients (adjusted hazard ratio [HR] 0.54, 95%CI 0.44-0.67). Other significant predictors of reported conversion rates included directly observed therapy (DOT) (P = 0.02), the number of drugs used in the therapy regimen (P = 0.001), and non-injectable drug use (P = 0.012). CONCLUSION: The rate of reported sputum culture conversion in TB patients was low, consistent with an earlier population-based report. The symbiotic relationship between HIV and mycobacterial infection might be a factor that compromised response to therapy in coinfected individuals.