Conventional interferon-α 2b verses hydroxyurea for newly-diagnosed patients with polycythemia vera in real world: a retrospective study based on 286 patients from a single center

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P169 A validated two-score system for interferon is a predictor of response to rituximab in SLE

Background/Aims We developed two interferon-stimulated gene (ISG) expression scores (IFN-Score-A and IFN-Score-B) that predict clinical outcomes in SLE better than a conventional “interferon signature”. IFN-Score-A includes the ISGs usually present in an interferon signature. IFN-Score-B includes additional ISGs responsive to multiple IFN subtypes and was better at predicting development of SLE among ANA-positive individuals, development of RA among CCP-positive individuals, and subclinical synovitis in SLE. Here, we investigate whether IFN-Score-A and IFN-Score-B predict response to Rituximab (RTX) therapy. The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK wide study enrolling patients undergoing treatment with RTX for active SLE despite previous treatment with cyclophosphamide or mycophenolate mofetil. MASTERPLANS is a consortium aimed at identifying therapeutic biomarkers in SLE. Methods We studied all BILAG-BR subjects undergoing their first cycle of RTX in whom a pre-treatment RNA sample was available. Disease activity was measured blind to biomarker status, using BILAG-2004. Response was defined as improvement in BILAG-2004 disease activity by at least one grade, with a maximum of one domain showing persistent BILAG-2004 grade B activity, and no new BILAG grade A or B disease flares at 6 months. Whole blood was collected into TEMPUS tubes and RNA extracted for measurement of IFN-Scores using a custom Taqman array as previously described. Multivariable logistic regression was used to test IFN-Scores and key baseline clinical covariates as predictors of response at 6 months. Results 147 patients were recruited, of whom there were 6 month BILAG data in 90. 59/90 (65.6%) were responders. In univariable and multivariable analysis, higher IFN-Score-B expression was significantly associated with clinical response (Table 1). Other characteristics typically associated with more severe SLE (younger age, African ancestry, and autoantibody repertoire) also independently predicted response. Conclusion High expression of interferon scores predicts better response to RTX. The novel IFN score-B was more predictive than a typical interferon signature. Future work will validate this biomarker in a replication cohort and integrate other with data on IFN biomarkers in other contexts. P169 Table 1:Baseline VariableNon respondersRespondersUnivariable OR (95% CI)P valueMultivariable OR (95% CI)P valueInterferon Score-A, median (IQR)-1.75 (-4.7,-1.0)-1.1 (-2.24,-0.1)1.21 (0.98,1.48)0.070.94 (0.58,1.53)0.81Interferon Score-B, median (IQR)-2.4 (-3.2,-1.6)-1.6 (-2.6,-1.11.56 (1.04,2.33)0.033.27 (1.39,7.68)0.007Age years, median (IQR)44 (38,52)38 (30,50)0.97 (0.94,1.00)0.060.92 (0.86,0.97)0.005African ancestry, n/N (%)8/31 (26)4/59 (7)0.21 (0.06,0.76)0.020.005 (0.000,0.22)0.006Numerical BILAG-2004, median (IQR)21 (20,25)18 (13,24)0.91 (0.86,0.93)0.010.80 (0.67,0.94)0.010Count of ANA subtypes, median (IQR)1 (1,3)2 (1,3)1.28 (0.84,1.95)0.252.38 (1.06,5.31)0.034Count of ANA subtypes is sum of positive Ro, La, Sm, RNP & dsDNA by local laboratories. Disclosure L.M. Carter: None. A. Alase: None. Z. Wigston: None. A. Burska: None. A. Psarras: None. Y. Yusof: None. J. Reynolds: None. M. Wittmann: Honoraria; Abbvie, Celgene, Janssen, L’Oreal, Novartis and Pfizer. I. Bruce: Consultancies; AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono. Member of speakers’ bureau; GlaxoSmithKline, UCB Pharma. Grants/research support; Genzyme Sanofi & GlaxoSmithKline. E.M. Vital: Honoraria; Roche, GSK and AstraZeneca. Grants/research support; Roche, GSK and AstraZeneca.

Safety and Efficacy of Fingolimod in Iranian Patients with Relapsing-remitting Multiple Sclerosis

Introduction: Fingolimod is the first confirmed oral immune-modulator to treat Relapsing-Remitting Multiple Sclerosis (RRMS). This study aimed to investigate the safety and efficacy of fingolimod therapy in Iranian patients with RRMS. Methods: In our trial, 50 patients resistant to conventional interferon therapy were assigned to receive fingolimod 0.5 mg per day for 12 months. The number of Dadolinium (Gd)-enhanced lesions, enlarged T2 lesions, and relapses over 12 months were considered as endpoints and compared to baseline. Liver biochemical evaluations and lymphocyte count were done at baseline and in months 3, 6, and 12 of the study. Patients were also monitored for possible cardiovascular events within the first 24 h and other side effects routinely. Results: Among the patients who completed the trial, the number of Gd-enhanced and enlarged T2 lesions over 12 months significantly decreased (P=0.03 and P<0.001, respectively). The proportion of relapse-free patients was higher compared to the onset of fingolimod administration. There were no significant alterations in the Expanded Disability Status Scale (EDSS) scores. A slight, transient increase was recorded in liver enzymes among the participants. Lymphocyte count reduced by 61% at month 1 and displayed a gradual increase until month 12. No bradycardia and macular edema were recorded. Conclusion: These findings indicate an effective first-line fingolimod therapy for the first time in Iranian patients with RRMS. The decrease in the number of new attacks and the amelioration of MRI lesions were the benefits of fingolimod therapy, suggesting that it is preferred to other medicines to treat RRMS in Iran.