Adalimumab regulates intracellular TNFalpha production in patients with rheumatoid arthritis

IntroductionAdalimumab is a fully human anti-tumour necrosis factor (TNF)alpha monoclonal antibody that specifically blocks the interaction of TNFalpha with its receptors. It binds both soluble and transmembrane TNFalpha.

We hypothesized that blocking these TNFalpha signals regulates the altered TNFalpha production in rheumatoid arthritis (RA) patients.

Methods:
We compared, by flow cytometry, TLR-induction levels of membrane and intracellular TNFalpha in monocytes (iTNFalpha + CD14 + cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors.

Results:
Before starting the treatment, the percentage of iTNFalpha + CD14+ cells in patients was significantly lower than in healthy donors (33.16 +/- 4.82 vs 66.51 +/- 2.4%, P

After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFalpha and a progressive increase in iTNFalpha + CD14+ cells in 10 patients with a good/moderate EULAR response. Levels of iTNFalpha + CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors.

In two patients, iTNFalpha + CD14+ cell upregulation was not observed and EULAR response did not improve. The first patient developed anti-adalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFalpha.

In the second patient, adalimumab was discontinued due to adverse effects and iTNFalpha + CD14+ cells then decreased to levels before treatment.

Conclusions:
Our findings suggest that adalimumab treatment in RA patients can return intracellular TNFalpha levels to that of healthy donors. This effect was not observed in the presence of neutralizing anti-adalimumab antibodies.

Author: Carlos Zamora-AtenzaCesar Diaz-TorneCarme GeliCesar Diaz-LopezM Angels OrtizPatricia MoyaIvan CastellvÃƒÂJuan C NietoElisabet CantÃƒÂ³Jordi CasademontCandido JuarezJosep M LlobetSilvia Vidal
Credits/Source: Arthritis Research Therapy 2014, 16:R15

Published on: 2014-07-18

News Provider: 7thSpace Interactive / EUPB Press Office

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