Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

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BackgroundThe problem of axial spondyloarthritis’ (axSpA) differential diagnostics is not solved, especially in the early stages of the axSpA. Therefore, new diagnostic markers for axSpA are needed.Objectivesof the study were to evaluate the prevalence, sensitivity and specificity of anti-CD74 autoantibodies (anti-CD74-AB) in HLA-B27 associated axSpA in comparison with HLA-B27 associated axial Psoriatic arthritis (axPsA) and with healthy controls.MethodsAnti-CD74-AB (quantitative ELISA) were measured in serum of 114 HLA-B27-positive patients with axSpA, and in 26 age- and sex – matched HLA-B27 positive patients with axPsA, and in 37 healthy controls without HLA-B27. 68 axSpA patients had ankylosing spondylitis (AS) according mNew-York criteria (1984), 46 axSpA persons had non-radiographic axSpA (nr-axSpA) due to ASAS criteria for axSpA (2009). AxPsA patients had psoriatic arthritis with axial involvement and fulfilled both CASPAR (2006) and ASAS axSpA criteria (2009). Disease activity in axSpA and axPsA patients was measured according ASAS recommendations.1 ResultsPatients with AS, nr-axSpA and axPsA were comparable in SpA activity: differences in BASDAI, ASDAS indices and C-reactive protein levels were not significant, p≥0.05 for all. Nr-axSpA patients had shorter disease duration as compared with AS and axPsA patients (p<0.001).The concentration of anti-CD74-AB in patients with axSpA was 3.5±3.0 U/ml (3.1±3.0 U/ml in AS and 3.8±2.9 U/ml in nr-axSpA patients), 2.1±1.4 U/ml in patients with axPsA (p≥0.05 compared to controls and ax-SpA)) and 1.3±1.4 U/ml in healthy controls (p<0.05 for the difference with ax-SpA, AS and nr-axSpA). Diagnostic values of anti-CD74-AB in axSpA (ROC-analyse results) are presented in table 1.Abstract THU0258 – Table 1Diagnostic values of anti-CD74 autoantibodies in patients with axial spondyloarthritis(ROC-analyse)AUC(95% CI)Sensitivity of the test,%Specificity of the test,%+LRUpper cut-off value for reference interval, U/mlp axSpA0,74 (0,67–0,82)64,489,25,9>2,0<0,0001AS0,68 (0,59–0,79)60,389,25,6>2,00001nr-axSpA0,78 (0,58–0,83)73,184,04,5>1,73<0,0001axPsA0,7 (0,69–0,89)96,145,91,80,70005AS - ankylosing spondylitis, axSpa - axial spondyloarthritis, axPsA – axial psoriatic arthritis, nr-axSpA - non-radiographic axial spondyloarthritis, CI - confidence interval,+LR – positive likelihood ratio.Cut-off value of anti-CD74-AB>2.0 U/ml in patients with axSpA showed the diagnostic sensitivity of 64.4%, specificity of 89.2%, the positive LR of 5.9, whereas in patients with nr-axSpA at concentrations of 1.7 U/ml - sensitivity 73.1%, specificity 84% and positive LR 4.5.ConclusionsConclusions. Anti-CD74-AB are strongly associated with nr-axSpA and less – axPsA. The measurement of anti-CD74-AB can be considered as candidate biomarker in the diagnostics of axSpA and in differential diagnostics between HLA-B27 positive ax-SpA and axPsA, especially in early stages of the diseases. Further studies are needed for the evaluation of anti-CD74-AB diagnostic capacity.Reference[1] Sieper J, et al. Ann Rheum D...

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by the occurrence of a wide range of autoantibodies (Aab) which can predict distinct clinical features of SSc. Aab to hnRNP A2 and its alternatively spliced variants B1 (anti-hnRNP B1) and B2 are generally referred to as anti-RA33 and have been extensively studied in rheumatoid arthritis (RA) [1]. However, the prevalence of anti-RA33 Aab in other autoimmune diseases, such as scleroderma, mixed connective tissue disease and systemic vasculitides, is far from determined [2–4]. Objectives To compare the frequency of anti-hnRNP B1 with other SSc-specific Aab and to determine an association thereof with the clinical phenotype in patients with SSc Methods We studied Aab prevalence in 64 patients with SSc, 29 with diffuse cutaneous SSc and 26 with limited cutaneous disease as well as 9 patients with overlap syndrome. Diagnosis of SSc in all patients was based on 1980 ACR (ARA) criteria and the disease phenotype was analyzed according to LeRoy's classification criteria [7]. Serum samples from clinically healthy blood donors (n=174) were used as a control group. Skin involvement and disease severity was measured with Rodnan's skin score and Valentini activity index. Vascular involvement was accessed by measurement of pulse wave velocity (PWV) and augmentation index (AI) with applanation tonometry (SphygmoCor system, AtCor Medical Pty Ltd., Sydney, Australia). Anti-hnRNP B1 IgG was assessed by an ELISA employing recombinant human hnRNP B1 expressed in E.coli (in.vent DIAGNOSTICA GmbH, Germany). SSc-specific Aab were measured with line immunoassay (Euroimmun AG, Germany) according to the manufacturer's instructions. Results Anti-hnRNP B1 were found in 18.5% (12/64) of SSc patients and in 1.1% (2/174) of controls (p<0.001). Median concentrations were also significantly higher in SSc patients (p<0.001). There were no significant associations of anti-hnRNP B1 level with any other particular SSc-specific Aab, clinical form of the SSc, degree of skin involvement, and clinical activity. We found that anti-hnRNP B1 antibodies directly correlated with the presence (r=0.33 p=0.009) of arterial hypertension and vessel-wall stiffness parameters like PWV (r=0.39, p=0.004) and AI (r=0.35, p<0.001). Conclusions Anti-hnRNP B1 (RA33) is an independent serological marker in SSc and is associated with vascular involvement. References Nell-Duxneuner Vet al. Ann Rheum Dis. 2010; 69(1):169-74. Tomoum HY et al. Pediatr Int. 2009;51(2):188-92. Siapka Set al. Autoimmunity. 2007;40(3):223-33. Cho SBetal.J Invest Dermatol. 2012;132:601-8. Hoffmann MH et al. J Immunol. 2007;179(11):7568-76. Steiner Get al. ClinExpRheumatol. 2002 Jul-Aug;20(4):517-24. LeRoy EC, et al. J Rheumatol 1988; 15:202-205. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2222