There was a significant interaction between saquinavir, ritonavir and rifampicin, with reduction in median plasma concentrations of saquinavir and ritonavir. Saquinavir should be given with caution in patients receiving rifampicin. Twice-daily dosing or higher saquinavir doses in once-daily administration should be tested to obtain more appropriate plasma levels.

The combination of ATV and LPV/RTV provided high plasma concentrations of both PI, which seemed to be appropriate for patients with multiple prior therapeutic failures, yielding good tolerability and substantial antiviral efficacy.

Background:Efficacy and safety profile of new JAK inhibitors have been properly defined by several clinical trials, being tested in many patients with Arthritis Reumatoid. However, real-life conditions studies play an important role in order to know JAK inhibitors behaviour in safety.Objectives:To describe adverse events of JAK inhibitors in patients with Arthritis Rheumatoid and asses the survival in relation to adverse events.Methods:Observational, descriptive, retrospective design performed in patients with Arthritis Reumatoid in follow-up by the Rheumatology department of the Hospital de Valme until January 2019. Demographic and clinical data related to safety has been collectedResults:58 patients were included with a mean age of 57,77 ± 10,78 years. Mean time from diagnosis was 8,7 ± 6,54 years, female predominance (75%). Mean ASDAS at the beginningof JAK inhibitor treatment was 4,76 ± 0,93. Regarding the determination of FR and CCCP 69% and was positive in both cases. Baricitinib was the treatment chosen in 13 patients (22.4%), and Tofacitinib in 45 patients (77.6%). Regarding associated treatments: 84.5% was under low-dose steroids theraphy; 77.6% was under combined therapy with at least 1 DMARD; 15.5% with two of them. Metotrexato was used in 53,4% of patients, leflunomide in 19%, hydroxycloroquine in 13.8%, sulfasalazyne in 12.1%. 72,4% have been before under at least one biologic treatment (frequently antiTNF), 41,1% one of them, 15.5% two of them, 12.1% three and 1.7% four before starting Jak inhibitor therapy. Adverse events has been observed in 17 patients (13 from de Tofacitinib group -28.8%-, and 4 in the Baricitinib group -30.76%). The most common advers events were: herpes zoster infections (4 patients in Tofacitinib group), respiratory infections (3), urinary infections (2), cutaneous (3), caphalea (1), legs oedema (2), toxic hepatitis in 1 patient of Baricitinib group; pulmonary thromboembolism was observed in 1 patient of Tofacitinib group, and atrial fibrillation in other patients of that group. Treatment was interrupted in 24 of 58 patients (mean time 8.92 ± 5.14 months), 16 from Tofacitinib group (35.5% of patients with Tofacitinib) and 8 from Baricitinib group (61.15% of patients with Tofacitinib). In Tofacitinib group, 10 patients stopped therapy for inefficacy reasons and 6 for advers effects related. In Baricitinib group, 5 due to inefficacy, 2 to adverse effects and 1 to clinical remission.Conclusion:Main adverse effect were mild-moderate infections (involving in-hospital treatment only in one Barictinib group patient). One pulmonary thromboembolism has been detected in a hypertensive 70 years old patient, supporting the recent recommendation of avoiding these drugs in patients over 65 or with cardiovascular risk factors. It is remarkable low survival results due to inefficacy, that could be related to clinical profile of refractory patients in our study, and/or to the small sample that we describe.Disclosure of Interests:None declared

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BackgroundInterleukin (IL)-1 and IL-6 are pivotal cytokines in the pathogenesis of adult-onset Still's disease (AOSD).ObjectivesCompare the efficacy and safety of tocilizumab (TCZ) versus anakinra (ANK) given for at least 1 year to AODS patients refractory to conventional treatment.MethodsMulticenter study (31 hospitals) of 75 patients (TCZ; n=34 and ANK; n 41) with AODS refractory to conventional immunosuppressive drugs and in many cases also to other biological agents.ResultsComparisons of the group of patients with TCZ and ANK were: a) Average age: 39±16 vs. 34±14 years (p=0.2) b) Percentage of women: 76.5% vs. 63.4% (p=0.2) c) Median disease duration 4.2 [1-9] vs. 2.2 [0.3 to 4.9] years (p=0.14) d) Average dose of prednisone 15±9.9 mg/day vs. 28.3±22 mg/day (p=0.013) e) Median of conventional immunosuppressants (2 [1-3] vs 1 [1-2] (p=0.05) f) Median of other biological therapies: 1 [0-2] vs. 0 [0-1] (p=0.04). The initial dose of i.v. TCZ were: 8 mg/kg/4 weeks (n=22), 8 mg/kg/2 weeks (n=10) and 4 mg/kg/4 weeks (n=2). ANK dose was 100 mg/day s.c. Both biologic agents were often combined with a conventional immunosuppressive drug (55.9% vs 70.7%; p=0.2). Both biologic agents yielded a quick and sustained improvement of all clinical and laboratory parameters (Table). The improvement in the clinical parameters was similar in both groups. However an earlier improvement of CRP and ESR was observed following TCZ therapy. After a median follow-up of 19 months [12-31] with TCZ and 15.5 months [4.5 to 50] with ANK (p=0.1), the major adverse effects in the TCZ group were: elevation liver enzymes (n=4), mild to moderate leucopenia (4), upper respiratory tract infection (3), pneumonia (1), pyelonephritis and severe enterocolitis (1) and spondylodiscitis (1). In the group of ANK: skin lesions (n=8), mild leucopenia (3), myopathy (1), respiratory infection by P. aeruginosa and gluteal abscess (1), herpes zoster (1), osteomyelitis (1) and infection of urinary tract (2). While none of the TCZ-treated required discontinuation of the drug due to inefficacy, ANK had to be discontinued for this reason in 11 patients (p=0.001). Adverse effects leading to discontinuation of the drug were observed in 2 patients with TCZ and 4 patients with ANK (p=0.54).ConclusionsTCZ and ANK are associated with a rapid and sustained clinical improvement in most patients with refractory AODS. However, TCZ appears to be more effective than ANK.Disclosure of InterestNone declared