Skip to main content
main-content

01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Arthritis Research & Therapy 1/2017

Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 1/2017
Autoren:
T. W. J. Huizinga, A. Batalov, R. Stoilov, E. Lloyd, T. Wagner, D. Saurigny, B. Souberbielle, E. Esfandiari
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13075-017-1267-3) contains supplementary material, which is available to authorized users.

Abstract

Background

Namilumab (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.

Methods

Adults 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.

Results

Patients 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).

Conclusions

Subcutaneous namilumab was generally well tolerated. Although namilumab demonstrated preliminary evidence of efficacy, patient numbers were small; phase 2 studies are ongoing.

Trial registration

ClinicalTrials.gov, NCT01317797. Registered 18 February 2011.
Zusatzmaterial
Additional file 1: Figure S1. PRIORA study design. D day (PDF 7 kb)
13075_2017_1267_MOESM1_ESM.pdf
Additional file 2: Figure S2. Flow diagram showing patient disposition. DMARDs disease-modifying antirheumatic drugs, HIV human immunodeficiency virus, IgG, immunoglobulin G (PDF 16 kb)
13075_2017_1267_MOESM2_ESM.pdf
Additional file 3: Figure S3. Change from baseline in swollen (a) and tender (b) joint counts. *Error bars show upper SE for placebo and lower SE for namilumab. SE standard error, SJC swollen joint count, TJC tender joint count. (PDF 1292 kb)
13075_2017_1267_MOESM3_ESM.pdf
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2017

Arthritis Research & Therapy 1/2017 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Meistgelesene Bücher aus der Inneren Medizin

2017 | Buch

Rheumatologie aus der Praxis

Entzündliche Gelenkerkrankungen – mit Fallbeispielen

Dieses Fachbuch macht mit den wichtigsten chronisch entzündlichen Gelenk- und Wirbelsäulenerkrankungen vertraut. Anhand von über 40 instruktiven Fallbeispielen werden anschaulich diagnostisches Vorgehen, therapeutisches Ansprechen und der Verlauf …

Herausgeber:
Rudolf Puchner

2016 | Buch

Ambulant erworbene Pneumonie

Was, wann, warum – Dieses Buch bietet differenzierte Diagnostik und Therapie der ambulant erworbenen Pneumonie zur sofortigen sicheren Anwendung. Entsprechend der neuesten Studien und Leitlinien aller wichtigen Fachgesellschaften.

Herausgeber:
Santiago Ewig

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin 

Bildnachweise