Feasibility of TNF-Inhibitor Dose Reduction in Patients with Psoriatic Arthritis and Ankylosing Spondylitis

New research indicates that most psoriatic arthritis patients can maintain low disease activity on reduced doses of tumor necrosis factor inhibitors (TNFis) — but patients who experience flares after switching to the lower dose can struggle to regain control over their disease.

Investigators recruited 15 psoriatic arthritis patients whose disease activity score in 28 joints (DAS28 ESR) remained at or below 3.2 for 6 months or more and another 33 ankylosing spondylitis patients whose Bath ankylosing spondylitis disease activity index (BASDAI) had remained under 4 for the same period.

The investigators then lowered each patient’s TNFi dosage by a third. Patients who fared well continued on the lower dose indefinitely. Patients who experienced flares (defined as index scores above the threshold levels above) resumed standard TNFi doses.

Overall, 9 of the 15 psoriatic arthritis patients (60%) and 19 of the 33 ankylosing spondylitis patients (58%) remained on the lower dose for a mean period of 1 year (standard deviation, 0.8 years).

Among ankylosing spondylitis patients who experienced flares during the study period, the resumption of standard TNFi doses brought disease activity back down. After 24 weeks of treatment at the higher dose, there were no significant differences in BASDAI scores between patients who flared (mean score, 2.4; standard deviation, 1.1) and patients who maintained low disease activity on less medication (mean score, 1.9; standard deviation, 1.5; p=0.229).

The same was not true for psoriatic arthritis patients. Those who resumed normal medication doses after experiencing flares had significantly higher disease activity than those whose disease activity remained low.

After 24 weeks on the higher dose, patients still had a mean DAS28-ESR score of 2.7 (standard deviation, 0.6) while patients who remained stable on the lower dose had a mean DAS28-ER score of 1.3 (standard deviation, 0.5; p < 0.001).

“In a real-world setting, 60% of individuals with severe ankylosing spondylitis and psoriatic arthritis who achieve low disease activity can successfully reduce the dose of TNFi therapy by a third for a mean of 1 year,” the study authors wrote in Rheumatology. “In psoriatic arthritis, a lower DAS28-ESR prior to dose reduction of TNFi was associated with more successful dose reduction.”

At least 1 other study has found that a significant number of psoriatic arthritis patients fare well on reduced doses of TNFis.

A 2012 Biologics article reported that 47 of 53 psoriatic arthritis patients who had achieved remission on full doses of adalimumab maintained that response on half doses over a mean follow-up period of 28.9 months. (The superior results in this earlier study may reflect the patient population: people with early psoriatic arthritis who achieved full remission before dose reduction.)

There is also evidence that some patients with related conditions such as rheumatoid arthritis can safely reduce treatment doses. A 2015 paper from the Annals of the Rheumatic Diseases compared outcomes among 73 stable patients who maintained etanercept doses, halved them or received placebo instead. Nearly 90% of the placebo patients failed to maintain disease control but rates were similar among those on full (48%) and half (56%) doses.

If medication doses can be reduced without worsening outcomes, the potential cost savings are significant. Patients would also benefit from lower toxicity and less frequent trips to care providers.