Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials.
Objectives
To describe new-onset inflammatory bowel diseases (new IBD) in patients treated with interleukin 17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life.
Methods
A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case–control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease.
Results
31 cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and 4 patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5–7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). 2 patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 PY (7/1010) in 2016, to 0.08/100PY (6/7951) in 2019. No previous treatment with etanercept (OR = 0.33, IC95% 0.14–0.80, p= 0.014) and low number of previous biological therapies (OR = 0.67, 95%CI 0.47–0.94, p= 0.021) were significantly associated with new IBD.
Conclusion
The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.
О р и г и н а л ь н ы е и с с л е д о в а н и я 1 Национальный Центр кардиологии и терапии (НЦКТ) им. академика М. Миррахимова, Бишкек, Кыргызская Республика; 2 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»,
systemic lupus erythematosus (SLE) largely depends on migration of pulmonary artery smooth muscle cells (PASMCs). In this study, we tested whether IgG from SLE with PAH have stimulatory effects on PASMC migration. Methods Sera from 6 SLE patients, including 1 with PAH, and 7 healthy subjects were collected, and IgG was purified using protein A or protein G. PASMC migration was examined by a Boyden chamber method. Lamellipodia formation and antibody binding sites in the cells were examined by immunocytochemistry. Identification of anti-enolase1 antibodies was performed by immunoprecipitation, western blotting, mass spectrometry, and ELISA. Results IgG from SLE with PAH significantly increased migration of PASMCs than those without PAH in a concentration dependent manner (p<0.001). After incubation with IgG, the number of cells with lamellipodia, which represents rearrangement of the cytoskeleton necessary to migration, was 1.4-fold higher in SLE with PAH than those without PAH (p<0.01). In immunocytochemistry, IgG from SLE with PAH were colocalized with b-tubulin in the cytoplasm of PASMCs, and western blotting showed that the antibodies bound to a~50 kD protein in the lysates, which was subsequently identified as enolase1 reported to be involved in cell migration. Furthermore, the titer of IgG anti-enolase1 antibodies was 1.5-fold higher in SLE patients with PAH than those without PAH. Conclusions IgG from a patient with SLE accompanied by PAH promoted a migration of PASMCs, which is possibly ascribed to autoantibodies to enolase1.
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