Low Dose Treatment in Ankylosing Spondylitis Still Effective Save

About one-third of ankylosing spondylitis patients who cut their etanercept (Enbrel) dose in half maintained responses over 4 years, compared with two-thirds who stayed on standard therapy, researchers reported.

A majority of people who experienced disease regression were able to re-establish control when they returned to the original dose, Lauren Steel from Norfolk and Norwich University Hospital reported at the British Society for Rheumatology annual meeting.

Etanercept is commonly used to manage pain and other symptoms of ankylosing spondylitis. Biologics are expensive, and dose tapering could potentially reduce the risk of side effects and lead to considerable cost savings, Steel said during a poster discussion.

The ANSWERS trial (ANkylosing Spondylitis With Etanercept RegimeS) evaluated whether patients with active ankylosing spondylitis could safely reduce their etanercept dose.

The study included 47 patients with sufficient clinical response to the standard etanercept dose of 50 mg once weekly, defined as a reduction in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and spinal pain visual analog scores by at least 2 units.

Participants were randomly assigned to either stay on the 50 mg dose or taper to 25 mg. As previously reported in the Journal of Rheumatology, 52% of patients in the 25-mg arm maintained clinical responses at 6 months, compared with 83% of those who stayed on the full dose.

Steel presented findings from an extension study looking at longer-term follow-up through 50 months. Study participants who maintained clinical responses stayed on 25 mg etanercept, while those who experienced loss of disease control returned to the 50-mg dose.

The 4-year analysis included 12 patients in the 25-mg dose arm and 21 people in the 50-mg arm. Three-quarters in the low-dose arm and 95% in the high-dose arm were men and the median ages were 52 and 60 years, respectively.

Steel reported that 33.3% of participants randomized to the 25-mg arm had sustained responses at 50 months, compared with 66.6% of those who never reduced their dose. The median BASDAI score was somewhat higher in the low-dose group (2.8 versus 1.9, respectively).

In the low-dose group, 58.3% experienced disease flares and were reinstated on the 50-mg dose and one person stopped treatment due to side effects. They returned to the higher dose after an average of 16 months. Five of seven patients (71.4%) were able to "recapture" low disease activity within 14 months, according to Steel. The rest switched to adalimumab (Humira).

In the high-dose group, one person experienced flares, one discontinued etanercept due to side effects, two stopped after developed inflammatory bowel disease, and three were lost to follow-up.

"Although a minority of patients maintained response to the lower dose of etanercept over the longer term, the cost savings were substantial," the researchers concluded. They calculated the savings at £17,874 (approximately $23,000) per patient at 50 months.

Asked whether patients would do the trial again after being put through this, co-author Karl Gaffney, MB, from Norfolk and Norwich University Hospital in England said that many patients being treated for ankylosing spondylitis ask to come off treatment or reduce their drug doses.

"There's a big appetite for dose tapering," Gaffney said. "We didn't have any problem recruiting patients -- they wanted to be in the study for dose reduction."

Another option for reducing drug exposure would be to increase the length of time between 50 mg etanercept injections from once weekly to every 2 or more weeks. But the benefits of this approach are unknown, according to Gaffney.

"You could go another way, lengthening time between treatment," Gaffney said. "But the half-life of etanercept is 12 days, so I think it's better to reduce the dose. With some of the other [biologics] with a longer half-life, I think you could stretch it out to once a month or every 3 weeks. No one really knows the answer."