AS Patients Can Benefit from Switching Anti-TNF Therapies When One Stops Working, Study Suggests

Therapy with anti-tumor necrosis factor (anti-TNF) is highly effective in people with ankylosing spondylitis. But researchers suggest that patients whose treatment lost its effectiveness or resulted in adverse events can benefit from switching anti-TNF therapies.

These are the conclusions of a review study, “Ankylosing Spondylitis Treatment after First Anti-TNF Drug Failure,” published in the Israel Medical Association Journal.

Anti-TNF therapies have brought new relief to those with spondyloarthritis (SpA), but 20-30% of patients eventually stop responding properly and discontinue treatment, while 10-20% of patients stop taking their medication because their anti-TNF therapy has stopped working or from adverse effects.

There are a variety of anti-TNF agents available, including infliximab (Remicade), adalimumab (Humira, Imraldi), golimumab (Simponi), certolizumab (Cimzia), and etanercept (Enbrel).

These agents differ in their chemical structure and mechanism of action, which means that if one therapy no longer works for a patient, that patient can still respond to a different anti-TNF therapy.

Researchers gathered data from studies (randomized control trial, systematic review, and observational studies) conducted from 1999 to 2016, to characterize patients and treatment outcomes after the first anti-TNF failure among people with ankylosing spondylitis.

The National Danish (DANBIO) database included 432 patients, and the Norwegian database (NOR-DMARD; NCT01581294) included 77 patients, all of whom switched to a second anti-TNF drug.

Both registries revealed that most patients who switched were female, had a shorter duration of disease and symptoms, and a higher disease activity.

In addition, among those who switched, the effects of the first and second anti-TNF drug on disease activity were similar during the first year follow-up. But these registries included a higher proportion of patients achieving lower disease activity than other reports.

An earlier review study found that 30% of patients who start an anti-TNF therapy switch to a second one. However, the time between treatment initiation and discontinuation was not different between the first, second, and third anti-TNF drug.

Patients may stop responding to one anti-TNF agent because they start producing antibodies against this agent, an effect that seems to be dependent on the anti-TNF agent used.

Remicade, an antibody combining mouse and human proteins, induces the production of anti-drug antibodies more strongly than Humira/Symponi and Enbrel, both consisting of humanized proteins only.

Previous results indicate that 25.9% of spondyloarthritis patients produce anti-drug antibodies, mostly those treated with Remicade. 

Because the presence of antibodies against anti-TNF therapies can worsen patients’ response to therapy, evaluating anti-drug antibody levels in ankylosing spondylitis patients may help when deciding to switch therapies.

And, the effect of anti-drug antibodies on anti-TNF responses is stronger in ankylosing spondylitis patients than in those with other inflammatory diseases.

A study involving 1,159 patients with ankylosing spondylitis found that by the end of a 12-week treatment period with Humira, 57.2% of participants had reduced disease activity, and 27.7% had reached partial remission. Among the predictors for a positive outcome was no previous treatment with anti-TNF therapies.

Another study confirmed the effectiveness of Humira, Enbrel, or Remicade in ankylosing spondylitis either as a first or second anti-TNF therapy, but found that partial remission was less likely in patients with enthesitis (inflammation at tendon, ligament or joint capsule insertions), psoriasis, or low C-reactive protein levels, an indicator of inflammation.

Data from the National Swedish Biologics Registry showed that patients with ankylosing spondylitis stayed on their first anti-TNF drug longer if they were also treated with conventional disease-modifying rheumatic drugs (DMARDs).

Additional research indicates that 30.5% of spondyloarthritis patients remain on a first-line anti-TNF drug after 10 years, but more patients stay longer on Enbril than on Remicade and Humira.

Researchers conclude that although some studies are conflicting, they suggest that switching  anti-TNF therapies has become common practice in patients who fail their initial treatment. This trend is observed even though there are no published guidelines concerning the best strategy after a first anti-TNF failure.

“The most frequent reason for discontinuing is lack of efficacy but, regardless of the reason and the sequence of drugs administered, disease activity is reduced after switching,” researchers wrote, adding that “ankylosing spondylitis patients can be successfully treated with a second TNF antagonist.”