Session Information
Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Safety of Biologics and Small Molecules in Rheumatoid Arthritis
Session Type: Abstract Submissions (ACR)
Background/Purpose: TNFα-Inhibitors are the most widely used biological agents in rheumatic conditions or other chronic inflammatory diseases. Over the last ten years, the occurrence of lupus-like disease and the induction of antinuclear antibodies have been observed in more than 800 individuals receiving anti-TNFα-treatment worldwide. However, the exact incidence of serological changes and the frequency of associated clinical manifestations are unknown.
Methods: We conducted a single center, interdisciplinary prospective study on patients with RA, spondyloarthropathies and inflammatory bowel diseases who were elected for anti-TNFα-therapy as their first biological treatment. Clinical and serological parameters were collected before the first application and thereafter at six-monthly intervals. The evaluation included a clinical questionnaire and serological testing for ANA, dsDNA-antibodies and ANCA. We calculated the incidence rates based upon duration of drug exposure. The odds ratios within the subgroups were adjusted to the diagnosis or the compound with the lowest event rate, respectively.
Results: Between January 2011 and February 2014, 223 patients entered the study. The underlying diseases of these patients were RA (68), spondyloarthropathies (67), inflammatory bowel disease (84) and JIA (4). During the follow-up, 318 serum samples were collected, 117 of these were allotted to week 26, 89 to week 52, 51 to week 78 and 61 to week 104 of follow-up. – During the entire observation period, there was a continuous rise in ANA-titers and in the concentration of dsDNA-antibodies. The proportion of samples tested positive for ANA increased from 20 or 9.0% at baseline to 21 out of 56 or 37.5% respectively at week 104 (p=0.001). The proportion of samples with dsDNA-antibodies above the normal range (20 IU/ml) rose from none at baseline to 16 of 49 or 32.7% at the two year evaluation (p=0.0002), the average anti-dsDNA value increasing from 5.6 IU/ml to 18.5 IU/ml (p=0.004). These results were confirmed by a crithidia luciliae assay in 51.4% of these cases. 5 individuals or 2.5% of the study population additionally developed musculoskeletal symptoms assessed as lupus-like disease. These events required temporary termination of anti-TNFαtreatment and the application of corticosteroids. – When analyzing the impact of the various biologics and the co-medication, the highest seroconversion rate was observed in patients receiving infliximab (46.1%), followed by adalimumab (15.6%), certolizumab (8.2%) and etanercept (6.1%). In patients being treated with concomitant MTX (only rheumatic conditions were considered), the risk was lower (odds ratio 0.87) than in patients without MTX.
Conclusion: The present data confirm the capability of TNFα-inhibitors to induce both, clinically relevant lupus like disease and a high rate of seroconversion towards a lupus like antibody profile in a substantial proportion of patients. Our prospective study thus substantiates the hypothesis that these phenomena represent a systematic effect of TNFα-inhibitors, and that their incidence is higher than assumed by estimates based upon case reports.
Disclosure:
S. J. Winkelmann,
None;
R. A. Zeuner,
None;
D. Schuldt,
None;
J. Bethge,
None;
U. Mrowietz,
None;
M. Laudes,
None;
S. Schreiber,
None;
J. Schroeder,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incidence-of-clinical-and-serological-lupus-like-disease-during-anti-tnf%ce%b1-treatment-a-two-year-prospective-study-in-an-interdisciplinary-patient-cohort/