Journal Article

Clinical significance of high levels of soluble tumour necrosis factor-α receptor-2 produced by alternative splicing in rheumatoid arthritis: a longitudinal prospective cohort study

Juan D. Cañete, Carolina Albaladejo, Maria Victoria Hernández, Begoña Laínez, José A. Pinto, Julio Ramírez, Maria José López-Armada, José R. Rodríguez-Cros, Pablo Engel, Francisco J. Blanco and Raimon Sanmartí

in Rheumatology

Volume 50, issue 4, pages 721-728
Published in print April 2011 | ISSN: 1462-0324
Published online December 2010 | e-ISSN: 1462-0332 | DOI: https://dx.doi.org/10.1093/rheumatology/keq381
Clinical significance of high levels of soluble tumour necrosis factor-α receptor-2 produced by alternative splicing in rheumatoid arthritis: a longitudinal prospective cohort study

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Objectives. We investigated whether serum levels of an alternatively spliced soluble (s)TNF receptor-2 (DS-TNFR2) affected the clinical response to anti-TNF-α therapy, classical DMARDs or radiological evidence of disease progression in patients with RA.

Methods. We included 116 patients with RA. Cohort 1: 52 DMARD-naïve early RA patients [mean (s.d.) disease duration 8.5 (6.2) months] who started gold salts and MTX therapies. Cohort 2: 64 MTX-resistant established RA patients [144 (107) months] who started infliximab therapy. We evaluated the European League Against Rheumatism (EULAR) response to therapy and the serum levels of DS-TNFR2, sTNFR2 and ACPAs at baseline and at 12 months. In Cohort 1, radiological progression and levels of MMP-1 were also determined.

Results. In Cohort 1, 40% of patients had high baseline levels (HL > 50 ng/ml) of DS-TNFR2 with significantly higher RF and ACPA levels than patients with normal levels (NL ≤ 50 ng/ml) of DS-TNFR2. The EULAR response to DMARDs was similar in HL and NL patients. Radiographic progression was observed in 23.5% of all patients after 12 months. In Cohort 2, 26.6% of patients had HL of DS-TNFR2 with significantly higher RF and ACPA levels than patients with NLs. The EULAR response from 6 to 30 weeks was prolonged in the HL group compared with the NL group.

Conclusions. Patients with HL of DS-TNFR2 maintained a prolonged therapeutic response to anti-TNF-α therapy and had proportionally less radiographic progression compared with patients with NLs.

Keywords: Tumour necrosis factor receptors; Anti-tumour necrosis factor therapy; Synthetic disease-modifying anti-rheumatic drug; Rheumatoid arthritis; European League Against Rheumatism response; Radiographic progression

Journal Article.  4331 words.  Illustrated.

Subjects: Rheumatology

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