Session Type: Abstract Submissions (ACR)
Background/Purpose Response to tumor necrosis factor alpha (TNF-α) inhibition is variable in rheumatoid arthritis (RA). Previous studies have suggested that circulating type I interferon (IFN) levels may predict treatment response to TNF-α inhibitors and other biological agents in RA. Prediction of likely responders prior to initiating therapy would represent a major advance in biological treatment strategies for RA.
Methods We studied a test set of 32 RA patients from the ABCoN registry and a validation set of 80 RA patients from the TETRAD registry. All subjects had serum available prior to treatment with a TNF-α inhibitor. In the test set, only those with a good response or no response at 14 weeks by EULAR criteria were included. In the validation set, subjects were included from the EULAR good, moderate, and non-response categories defined at 12 weeks post-treatment. Pre-treatment total serum type I IFN activity as well as IFN-α vs. IFN-β activity were measured using a functional reporter cell assay.
Results In the test set, an increased ratio of IFN-β/IFN-α >1.3 in the pre-treatment serum sample was associated with lack of response by EULAR criteria at 14 weeks (p=0.009), and a receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. Similarly, higher IFN-β/IFN-α ratio was positively correlated with higher DAS score at 14 weeks in the test set (Spearman’s rho= 0.57, p=0.0075). In the validation set, subjects with an IFN-β/IFN-α ratio >1.3 were significantly more likely to have non-response by EULAR criteria at 12 weeks (p=0.0035), and no patient with this ratio or greater achieved a good response. In meta-analysis, IFN-β/IFN-α ratio >1.3 was a strong discriminator of good response vs. non-response at 12-14 weeks (OR = 18.0, p=7.4×10-5), and also a significant predictor of non-response vs. either moderate or good response at 12-14 weeks (OR = 4.34, p=0.0014). Anti-CCP antibody titer and mechanism of action (mAb vs etanercept) of TNF-α inhibitor did not influence this relationship.
Conclusion Increased pre-treatment serum IFN-β/IFN-α ratio was strongly associated with non-response to TNF-α inhibition by EULAR criteria at 12-14 weeks. This blood test may be useful in making treatment decisions using TNF-α inhibitors in RA and other diseases.
J. M. Dorschner,
M. A. Jensen,
T. Wampler Muskardin,
S. L. Bridges Jr.,
P. K. Gregersen,
T. B. Niewold,
Janssen Pharmaceutica Product, L.P., EMD Serono,
Biogen Idec, EMD Serono,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/baseline-serum-interferon-betaalpha-ratio-predicts-response-to-tumor-necrosis-factor-alpha-inhibition-in-rheumatoid-arthritis/