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- Tofacitinib-induced eosinophiliaPublication . Archer, Sara; Ferreira, Daniela; Ferreira, Ana Teresa; Ponte, Sofia; Caetano, Cidalina; Salgado, Marta; Lago, Paula; Pedroto, IsabelTofacitinib is an oral small molecule JAK inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC). Its efficacy and safety have been demonstrated in phase III clinical trials and supported by real-life data. We report the case of an 18-year-old woman with a 1-year diagnosis of left-sided UC, with multiple admissions due to disease exacerbation or infections, refractory to infliximab (with azathioprine) and currently under treatment with vedolizumab and tacrolimus. She was admitted due to a severe disease exacerbation and, because of a previous history of neuropsychiatric side effects to corticotherapy, tofacitinib was initiated. In the following 6 days, there was no clinical improvement of UC, and serial blood work-up revealed moderate grade persistent peripheral eosinophilia (3000 cells/mm3) and acute kidney injury grade 1 KDIGO. Tofacitinib temporary suspension was decided, with a rapid normalization of renal function/eosinophil levels. Tofacitinib was restarted 2 days after its suspension. However, she developed moderate eosinophilia (2000 cells/mm3) again, which was considered an adverse effect (AE) to tofacitinib, leading to its suspension with eosinophilia resolution. Given the severity of the disease, after a multidisciplinary discussion, it was decided to start high-dose corticotherapy and ustekinumab with maintenance therapy every 4 weeks, and to add tacrolimus. Clinical and biochemical remission were achieved, and the patient was discharged. Three-month follow-up after tofacitinib suspension showed no recrudescence of eosinophilia. Tofacitinib represents a significant advance in the management of UC patients. The drug has a good safety profile with few related AE. This case aims to warn about an adverse reaction to tofacitinib not reported so far, including in a multicenter real-life setting recently published by Hernández et al where eosinophilia is also not described, thus emphasizing the rarity of this AE. To our knowledge this is the first case of tofacitinib-induced eosinophilia in the context of UC.
- Rapid test detection of anti-infliximab antibodies: performance comparison with three different immunoassaysPublication . Rocha, Cátia; Lago, Paula; Fernandes, Samuel; Correia, Luís; Portela, Francisco; Vieira, Ana Isabel; Patita, Marta; Arroja, Bruno; Ministro, Paula; Alves, Catarina; Dias, Cláudia Camila; Magro, FernandoBackground and aims: Therapeutic drug monitoring (TDM) of infliximab (IFX) and anti-infliximab antibodies (ATIs) is essential for treatment optimisation in inflammatory bowel disease (IBD) patients. The aim of this study was to estimate and compare the agreement and accuracy between a new rapid test and three established enzyme-linked immunosorbent assays (ELISAs) to quantify ATIs levels, and to evaluate the impact of exogenous IFX on the performance of these assays. Methods: We analysed 200 serum samples from 57 IBD outpatients in IFX induction or maintenance therapy at six IBD centres in Portugal. ATI levels were quantified using the rapid test Quantum Blue® (QB) Anti-Infliximab (Bühlmann) and three established ELISAs: In-House, Theradiag (Lisa Tracker Anti-Infliximab), and Immundiagnostik (IDKmonitor Infliximab). ATIs were quantified in patients' serum samples and spiked samples with exogenous IFX, based on analytical and clinical cutoffs. Qualitative agreement and accuracy were estimated by Cohen's kappa (k) with 95% confidence intervals. Results: ATIs quantification with clinical cutoffs showed a slight agreement between QB rapid test and In-House [k = 0.163 (0.051-0.276)] and Immundiagnostik [k = 0.085 (0.000-0.177)]. Regarding IFX/ATIs status, the QB rapid test showed a substantial agreement with Theradiag [k = 0.808 (0.729-0.888)] and a fair agreement with In-House [k = 0.343 (0.254-0.431)] and Immundiagnostik [k = 0.217 (0.138-0.297)]. The QB rapid test could not detect ATI-positive levels in samples with exogenous IFX at 5-300 µg/ml. Interference on ATIs detection was observed at exogenous IFX ⩾30 µg/ml for In-house and Immundiagnostik assays. Conclusion: QB rapid test is only suitable to detect ATI-positive levels in the absence of IFX.
- Vedolizumab-associated psoriasis: until where does gut selectivity go?Publication . Guedes, Tiago Pereira; Pedroto, Isabel; Lago, PaulaInflammatory Bowel Disease and Psoriasis are chronic inflammatory diseases that share common genotype, clinical course, and immunological features, although its relationship is still unclear. We report a 34-year-old woman with ileal Crohn's disease diagnosed 14 years ago, with the development of extensive, exudative scalp lesions after adalimumab therapy. Biopsies from skin lesions were compatible with vulgar psoriasis. The patient reports no personal or family history of psoriasis. Due to persistence and further worsening of skin lesions, paradoxical etiology to adalimumab was presumed and the drug was stopped with complete resolution of skin lesions and intestinal disease in remission under methotrexate. Due to pregnancy-planification methotrexate was stopped and, 8 months-after, systemic steroid-therapy was introduced due to moderate-to-severe intestinal flare. Vedolizumab was started and at the second infusion patient reported hair loss with no other complaints. Twelve months after vedolizumab initiation the patient reported reappearance of the extensive scalp and peri-fistula psoriatic lesions. Topical therapy was started but unsuccessfully and given the progressive worsening of the lesions, vedolizumab was suspended, with skin improvement seen 1 month after discontinuation. There are few case-reports of vedolizumab acting as a trigger to some dermatological conditions in IBD-patients, including psoriasis. The molecular mechanism behind it isn't fully understood. We present and discuss, to our knowledge, the first case in the literature of psoriasis triggered by vedolizumab in Crohn's disease.
- Genetic Variants of the MGAT5 Gene Are Functionally Implicated in the Modulation of T Cells Glycosylation and Plasma IgG Glycome Composition in Ulcerative ColitisPublication . Pereira, Márcia S.; Durães, Cecília; Catarino, Telmo A.; Costa, José L.; Cleynen, Isabelle; Novokmet, Mislav; Krištić, Jasminka; Štambuk, Jerko; Conceição-Neto, Nádia; Machado, José C.; Marcos-Pinto, Ricardo; Magro, Fernando; Vermeire, Séverine; Lauc, Gordan; Lago, Paula; Pinho, Salomé S.Objectives: The impact of genetic variants (single nucleotide polymorphisms [SNPs]) in the clinical heterogeneity of ulcerative colitis (UC) remains unclear. We showed that patients with UC exhibit a deficiency in MGAT5 glycogene transcription in intestinal T cells associated with a hyperimmune response. Herein, we evaluated whether MGAT5 SNPs might functionally impact on T cells glycosylation and plasma IgG glycome in patients with UC, as well as in UC clinical outcomes. Methods: Three selected MGAT5 SNPs (rs3814022, rs4953911, and rs1257220), previously associated with severity of autoimmune disease or with plasma glycome composition in healthy individuals, were functionally evaluated in patients with UC through analysis of MGAT5 mRNA levels in colonic (n = 14) and circulating (n = 24) T cells and through profiling the plasma IgG Fc glycosylation (n = 152). MGAT5 SNPs were genotyped in 931 patients with UC from 2 European cohorts and further associated with patients' prognosis. Targeted next-generation sequencing for MGAT5 coding and regulatory regions was also performed. Results: MGAT5 SNPs were shown to be functionally associated with low transcription levels of MGAT5 in colonic and circulating T cells from patients with UC and with agalactosylation of IgGs, often associated with a proinflammatory phenotype. The SNPs rs3814022 and rs4953911 were further associated with the need of biologics. Next-generation sequencing data further revealed a combination of MGAT5 SNPs that stratify patients with UC according to their severity. Discussion: Our results revealed that MGAT5 SNPs have a phenotypic impact on T cells glycosylation and in plasma IgG glycome composition associated with UC pathogenesis. MGAT5 SNPs display a tendency in the association with a worse disease course in patients with UC.