Background/Purpose: Amyloidosis is often due to an underlying inflammatory disorder, such as rheumatoid arthritis (RA), with organ deposition of serum amyloid A (SAA).  Oral disease modifying anti-rheumatic drugs (DMARDs) and biologics can ameliorate RA, reduce SAA levels and improve amyloidosis.  Anti-tumor necrosis factor α (TNF) therapy has yielded remarkable benefits in case studies of patients with amyloidosis, and studies suggest TNF regulates SAA production. Our aim was to determine if RA patients treated with the TNF antagonist, etanercept, have greater reductions in SAA levels than RA patients treated solely with oral DMARD therapies. 

Methods: Samples were analyzed from RA subjects (n = 755) enrolled in the Treatment of Early RA (TEAR) study, a randomized, double-blind trial.  In the TEAR trial, early RA subjects with less than 2 years of disease duration were randomized to either combination etanercept (ETN)/methotrexate (MTX) therapy (n = 244), MTX/hydrochloroquine/sulfasalazine (triple oral) therapy (n = 132) or MTX monotherapy (n = 379).  MTX monotherapy subjects with a DAS28-ESR > 3.2 after 6 months of treatment were stepped up to either ETN/MTX (n = 205) or triple oral therapy (n = 93).  Serum samples and clinical data were collected when treatment was initiated and at 24, 48 and 102 week follow-up visits. The results from the TEAR trial indicated that there were equal reductions in disease activity in all arms of the study after two years of treatment.  A mixed effects model was used to determine whether ETN/MTX treatment compared to triple oral therapy differentially lowered SAA levels.  In addition to treatment, fixed effects in the model included time, baseline SAA levels, treatment*time and DAS28-ESR.

Results: There were no baseline differences in age, SAA level, CRP level, RF status, or disease duration between the different treatment arms of the TEAR trial. Overall, there were significant differences in SAA levels by both visit (p=0.0197) and treatment arm (p=0.0130).  SAA levels were lower by an average of 66 ranks following treatment with ETN/MTX compared to triple oral therapy.  Similar results were found for serum CRP levels by visit (p=0.0254) and by treatment (p < 0.0001), with an even more pronounced mean difference than SAA levels; serum CRP levels were lower by an average of 144 ranks following treatment with ETN/MTX compared to triple oral therapy. 

Conclusion: RA subjects treated with ETN plus MTX had a greater reduction in SAA levels than subjects treated with oral DMARD therapy, even after correcting for disease activity.  While the TEAR trial was not designed to study amyloidosis, our analysis suggests that RA patients with amyloidosis may derive greater benefit from treatment with TNF antagonists than oral DMARDs in clinical situations where both treatments lower disease activity to the same extent.  Interestingly, the differential effect of ETN plus MTX compared to triple oral DMARDs on SAA levels may be less pronounced than the differential effects of ETN plus compared to triple oral DMARDs on CRP levels.  The latter may be important when considering use of SAA versus CRP levels as biomarkers for disease activity during treatment with TNF antagonists.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-tumor-necrosis-factor-%ce%b1-therapy-etanercept-plus-methotrexate-lowers-serum-amyloid-a-levels-to-a-greater-extent-than-triple-oral-disease-modifying-anti-rheumatic-drug-therapy-in-early-rheum/