Abstract
Studies on autoantibody production in patients treated with tumor necrosis factor-α (TNF-α) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-α antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-β2 glycoprotein I (anti-β2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-β2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-β2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents.
Highlights
Clinical trials in rheumatoid arthritis (RA) have demonstrated that tumor necrosis factor-α (TNF-α) blocking agents are highly beneficial for most patients refractory to classic treatment with disease-modifying anti-rheumatic drugs [1,2,3,4]
No patients who were positive for anti-CCP or rheumatoid factor (RF) at baseline became negative after anti-TNF-α treatment, both RF serum titers and anti-CCP autoantibodies decreased significantly at week 24 (p < 0.01 and p < 0.01, respectively) and week 48 (p < 0.01 and p < 0.01, respectively) (Table 2)
When we grouped the patients on the basis of their clinical response (ACR improvement criteria) to adalimumab, a significant decrease in RF serum titers was observed in those who were clinically improved according to American College of Rheumatology (ACR) 20 and ACR 50 at weeks 24 and 48, whereas a decrease was found for ACR 70 at week 48 (Table 3)
Summary
Clinical trials in rheumatoid arthritis (RA) have demonstrated that tumor necrosis factor-α (TNF-α) blocking agents are highly beneficial for most patients refractory to classic treatment with disease-modifying anti-rheumatic drugs [1,2,3,4]. Arthritis Research & Therapy Vol 8 No 1 Atzeni et al. Recently, two papers showed a decrease in RF and anti-CCP antibody titers in patients with RA treated with infliximab [6,8]. Antinuclear (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibodies have been respectively described in up to 86% and 57% of patients with RA treated with the TNF-α blocking agent infliximab [3,7,12,13,14,15,16]. Lower percentages were reported in patients treated with etanercept [17] These autoantibodies were only anecdotally associated with clinical manifestations suggestive of a druginduced systemic lupus erythematosus [17]. ANA and anti-dsDNA autoantibodies have been reported at higher prevalence in patients treated with infliximab than in those treated with etanercept and in spite of the lack of any flare in a patient with previous infliximab-induced systemic lupus erythematosus when etanercept therapy was started, the occurrence of these autoantibodies has been considered a drug class-related side effect [17,18]
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