Browsing by Author "Freitas, J"
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- Lenalidomide is effective and safe for the treatment of patients with relapsed multiple myeloma and very severe renal impairment.Publication . João, C; Freitas, J; Gomes, F; Geraldes, C; Coelho, I; Neves, M; Lúcio, P; Esteves, S; Esteves, GPatients with multiple myeloma (MM) and severe renal impairment (SRI) have shorter survival than MM patients without renal failure. Although lenalidomide is a highly active drug, this immunomodulatory agent is frequently neglected in this context due to its predominant renal clearance and, consequently, an increased risk of toxicity. This risk might be overcome with the proper lenalidomide dose adjustment to renal function. This study evaluates the outcomes of 23 relapsed MM patients with SRI (baseline creatinine clearance (CrCl) <30 mL/min) treated with lenalidomide-dexamethasone (LenDex), including 56 % (13 patients) under hemodialysis. The median CrCl at start of LenDex was 19 mL/min; an overall response rate (partial response or better) of 56 % was obtained, with a median follow-up from start of LenDex of 52 months (8-79). The median time until maximal response was 4 months, and in 58 % (7/12), the response was longer than 2 years. Nine percent had renal improvement, but all the 13 patients on hemodialysis remained under treatment. LenDex was interrupted in three cases because of adverse events (infections and cutaneous events); 78 % of the patients were on thromboprophylaxis with aspirin. It is important to notice that, after initial dose adjustment of therapy, there should be a continuous process of dose adjustment, taking into account variations in renal function. Furthermore, lenalidomide dose adjustment should be made according to the individual tolerance, even with stable renal function. LenDex dose adjustment, according to these principles, does not negatively impact response and improves treatment tolerance. It has a clear potential to treat this group of patients and to induce long duration of responses [event-free survival (EFS) 20.5 m and overall survival (OS) 42.6 m].
- Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).Publication . Durães, C; Machado, J; Portela, F; Rodrigues, S; Lago, P; Cravo, M; Ministro, P; Marques, M; Cremers, I; Freitas, J; Cotter, J; Tavares, L; Matos, L; Medeiros, I; Sousa, R; Ramos, J; Deus, JR, et al.BACKGROUND: About 70 loci are associated with susceptibility to Crohn's disease (CD), particularly in pathways of innate immunity, autophagy, and pathogen recognition. Phenotype-genotype associations are inconsistent. METHODS: CD susceptibility polymorphisms ATG16L1 rs2241880, ICAM1 rs5498, IL4 rs2070874, IL17F rs763780, IRGM rs13361189, ITLN1 rs2274910, LRRK2 rs11175593, and TLR4 rs4986790 were genotyped in a Portuguese population (511 CD patients, 626 controls) and assessed for association with CD clinical characteristics. RESULTS: There is a significant association of CD with the single nucleotide polymorphisms (SNPs) in ATG16L1 (odds ratio [OR] 1.36 [1.15-1.60], P = 2.7 × 10(-6) for allele G), IRGM (OR 1.56 [1.21-1.93], P = 3.9 × 10(-4) for allele C), and ITLN1 (OR 1.55 [1.28-1.88], P = 4.9 × 10(-4) for allele C). These SNPs are associated with ileal location (OR, respectively, 1.49, 1.52, and 1.70), ileocolonic location (OR, respectively, 1.31, 1.57, and 1.68), and involvement of the upper digestive tract (OR, respectively for ATG16L1 and IRGM, 1.96 and 1.95). The risk genotype GG in ATG16L1 is associated with patients who respond to steroids (OR 1.89), respond to immunosuppressants (OR 1.77), and to biologic therapy (OR 1.89). The SNPs in ITLN1 and IRGM are both associated with a positive response to biologic therapy. The risk for ileal, ileocolonic, and upper digestive tract locations increases with the number of risk alleles (OR for three alleles, respectively, 7.10, 3.54, and 12.07); the OR for positive response to biologic therapy is 3.66. CONCLUSIONS: A multilocus approach using autophagy-related genes provides insight into CD phenotype-genotype associations and genetic markers for predicting therapeutic responses.