Adalimumab (Humira) regulates the production of the inflammatory protein TNFalpha

This study examined whether blocking TNFalpha can also regulate the production of TNFalpha in rheumatoid arthritis patients.

Tumor necrosis factor alpha (TNFalpha) is a protein mainly produced by monocytes (white blood cells). It can exist in 3 different states: inside cells (intracellular), attached to the outside of cells (membrane bound) or floating outside cells (soluble).

Levels of TNFalpha are high in the fluid surrounding joints in patients with rheumatoid arthritis. This contributes to the inflammation and damage that occurs in their joints. As a result, new drugs (such as adalimumab [Humira]) that block TNFalpha are used to treat patients. Adalimumab attaches to both soluble and membrane bound TNFalpha, which blocks TNFalpha activity. It is unclear whether adalimumab also regulates the levels of TNFalpha produced in rheumatoid arthritis patients. 

This study included 12 patients with rheumatoid arthritis and 5 healthy blood donors for comparison. Patients received an injection of adalimumab once every 2 weeks for 24 weeks. Changes in blood TNFalpha levels were analyzed after 4, 12 and 24 weeks of treatment. Any improvement in symptoms were also recorded.

Before starting the treatment, the percentage of monocytes positive for intracellular TNFalpha was lower in patients than in healthy donors (33.16% versus 66.51%). As expected membrane and soluble TNFalpha were blocked after 2, 6 and 12 adalimumab injections.

There was also a progressive increase in the number of monocytes positive for intracellular TNFalpha in 10 of the patients. After 12 injections these 10 patients had similar percentages of monocytes positive for intracellular TNFalpha as healthy donors (60.68% versus 66.51%). These patients also had reduced symptoms of rheumatoid arthritis after treatment (less swollen and tender joints).

The same increase was not seen in 2 patients. The first patient developed new proteins (anti-adalimumab antibodies) which blocked the drug and prevented it from working. The second patient stopped treatment due to adverse effects (allergy).

The authors concluded that adalimumab can return intracellular TNFalpha levels in rheumatoid arthritis patients to levels seen in healthy donors.