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ObjectivesTo determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA).MethodsPatients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety.ResultsOf the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters.ConclusionsMOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases.Trial registration numberNCT01023256

Biochemical markers reflecting joint remodeling in osteoarthritis (OA) are a promising diagnostic tool. The aim of this study was to investigate serum levels of candidate biomarkers in subjects with and without knee OA and assess their correlation with clinical parameters and knee structural damage. 56 patients with primary knee OA and 31 healthy controls participated in this study. Patients were separated into two groups: isolated knee OA and generalized OA. Clinical parameters were obtained by validated self-reported questionnaires and a visual analogue scale. Serum levels of cartilage oligomeric protein (COMP), matrix metalloproteinase-3 (MMP-3), and Coll2-1 were quantified by enzyme-linked immunosorbent assay. Knee structural damage was determined by plain X-ray and 1.5 T magnetic resonance imaging (MRI), using Kellgren-Lawrence (KL) grading scale and Whole-Organ Magnetic Resonance Imaging Score (WORMS), respectively. Compared to controls, patients had significantly higher median serum COMP (985 vs. 625 ng/ml; p < 0.001) and MMP-3 (36.85 vs. 22.10 ng/ml; p = 0.003) levels. Patients with radiographic evidence of KLII/III knee OA had greater median COMP levels than KLI patients (1095 vs. 720 ng/ml; p = 0.001). In the generalized OA group, mean MMP-3 levels were higher than in the isolated knee OA group (30.40 vs. 55.13 ng/ml; p < 0.001). COMP correlated positively with WORMS (r = 0.454, p< 0.001) and MMP-3 (r = 0.337, p = 0.003). Cut-off values for serum COMP and MMP-3 were determined. We observed higher serum COMP and MMP-3 levels in knee OA patients compared to controls. COMP may reflect knee structural damage, while MMP-3-OA "generalization".

BackgroundNamilumab (AMG203) is an immunoglobulin G1 monoclonal antibody that binds with high affinity to the GM-CSF ligand. This was a phase 1b, randomized, double-blind study (PRIORA) to assess namilumab in active, mild-to-moderate rheumatoid arthritis (RA). The primary outcome was the safety and tolerability of repeated subcutaneous injections of namilumab in patients with mild-to-moderate RA.MethodsAdults with mild-to-moderate RA on stable methotrexate doses for ≥12 weeks were eligible. Patients received three subcutaneous injections of namilumab 150 or 300 mg, or placebo on days 1, 15, and 29, with 12 weeks’ follow-up. Primary objective was safety/tolerability.ResultsPatients in cohort 1 were randomized to namilumab 150 mg (n = 8) or placebo (n = 5). In cohort 2, patients were randomized to namilumab 300 mg (n = 7) or placebo (n = 4). Incidence of treatment-emergent adverse events (TEAEs) was similar across the three groups (namilumab 150 mg: 63%; namilumab 300 mg: 57%; placebo: 56%). TEAEs in ≥10% of patients were nasopharyngitis (17%) and exacerbation/worsening of RA (13%). No anti-namilumab antibodies were detected. The pharmacokinetics of namilumab were linear and typical of a monoclonal antibody with subcutaneous administration. In a post hoc efficacy, per protocol analysis (n = 21), patients randomized to namilumab showed greater improvement in Disease Activity Score 28 (erythrocyte sedimentation rate and C-reactive protein [CRP]), swelling joint counts and tender joint counts compared with placebo. Difference in mean DAS28-CRP changes from baseline between namilumab and placebo favored namilumab at both doses and at all time points. In addition area under the curve for DAS28-CRP was analyzed as time-adjusted mean change from baseline. A significant improvement in DAS28-CRP was shown with namilumab (150 and 300 mg groups combined) compared with placebo at day 43 (p = 0.0117) and also 8 weeks after last dosing at day 99 (p = 0.0154).ConclusionsSubcutaneous namilumab was generally well tolerated. Although namilumab demonstrated preliminary evidence of efficacy, patient numbers were small; phase 2 studies are ongoing.Trial registrationClinicalTrials.gov, NCT01317797. Registered 18 February 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1267-3) contains supplementary material, which is available to authorized users.