Does Rheumatoid Factor Influence Anti-TNF Responses in RA? Save

Smolen and colleagues have published a subanalysis of the EXXELERATE study that showed while certolizumab pegol [CZP] concentrations and efficacy  was unaffected by high titers of rheumatoid factor (RF), patients treated with adalimumab had a blunted response in the face of high RF titers.

At issue in this trial is whether Fc receptor binding by high titers of RF would differentially affect of CZP (without an Fc fragment) or ADA (Fc-containing TNFi).

The phase 4 EXXELERATE trial was a 2 year, randomized head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, the read out was drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3).

The outcomes compared 453 CZP-treated and 454 ADA-treated patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). After week 12, ADA concentration were lower in patients with the highest RF (>204 IU/ml) compared to those with RF ≤204 IU/ml. By comparison the CZP concentrations were similar, regardless of RF quartiles. 

Similarly the disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. But for patients with high RF (>204 IU/ml) the mean DAS28-CRP was significantly lower in CZP-treated vs ADA-treated patients. 

These analyses suggested that very high titers of RF may interfered with monoclonal antibody based therapies with an intact Fc receptor.  Repeated analyses of this phenomenon should be investigated to understand the applicability of these findings.