Reducing the dose of TNF blockers by about half is nearly as effective as the standard dose taken by ankylosing spondylitis patients who are in stable remission, a clinical trial shows.
Reducing dosage could also potentially reduce side effects.
The study, “Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis,” was published in the journal Arthritis Research & Therapy.
Spondyloarthritis (SpA) is a type of arthritis that affects mainly the spine and, in some cases, the arm and leg joints. When the spine and pelvic joints are the predominantly attacked regions, the disease is referred to as axial spondyloarthritis, of which the most common form is ankylosing spondylitis (AS).
First line treatment for SpA combines physical therapy and non-steroidal anti-inflammatory drugs (NSAIDs) for relieving symptoms and improving mobility.
But for patients who do not respond to NSAIDs, other medications are prescribed including a type of biologics called tumour necrosis factor (TNF) inhibitors, also known as TNF blockers or anti-TNF therapy. These biological medicines often work to maintain long-term clinical remission, which is considered the absence or near absence of signs and symptoms of the disease.
However, prolonged use of TNF inhibitors comes with some issues: they chronically shut down immune response (increasing the risk of serious infections) and can create a financial burden because of their cost.
Some evidence suggests that TNF blockers may be tapered down, with little impact on their efficacy, for patients in remission. However, data pointing towards this conclusion is scarce and not robust enough.
Therefore, researchers at Universitat Autònoma de Barcelona designed a Phase 4 clinical trial, REDES-TNF (NCT01604629), to determine if reducing the dose of TNF blockers could be just as effective as standard doses at maintaining low disease activity in patients in stable remission.
Several Spanish centers were sites for the study, which enrolled 126 patients with axial spondyloarthritis who had been in clinical remission for at least six months with a standard-dose TNF inhibitor. Patients had a mean age of 45.6 years, and most (84.1%) were men.
Participants were randomized to continue on the same TNF-inhibitor dose schedule, or to reduce their dosage to nearly half.
Anti-TNF therapies used included adalimumab (brand names Humira, Amjevita, Cyltezo, Hyrimoz, Imraldi), etanercept (brand names Brenzys, Enbrel, Erelzi), infliximab (brand names Flixabi, Inflectra, Ixifi, Remicade, Renflexis), and golimumab (brand name Simponi).
The main goal of the study was to measure the proportion of subjects with low disease activity — based on physician and patient global assessments and validated scales — after one year.
The results showed that at the end of one year, 83.8% of patients (47 of 55) assigned the full-dose regimen, and 81.3% of patients (48 of 58) who took a reduced dose maintained low disease activity.
The difference between the groups was small enough (less than 2.5%) to support that a reduced dose of TNF inhibitors is non-inferior to the standard dose for patients in remission. This means that the reduced dose is only marginally worse than the standard dose — a difference small enough for researchers to consider the reduced dose practically as good as the conventional dose.
The same tendency was true for clinical remission rates — 83.7% of patients given the full dose compared with 78.2% in the reduced-dose group were in clinical remission. (Clinical remission is considered more restrictive in definition than low disease activity).
In the study, clinical remission was defined as a BASDAI score of two or lower, no clinically active arthritis or joint inflammation, and normal laboratory markers of inflammation (C-reactive protein).
Serious adverse events or infections were observed in seven out of 62 patients (11.3%) who received a full dose and in two out of 61 patients (3.3%) assigned a reduced dose. Although not statistically significant, this difference suggests that low doses of TNF blockers may be safer, especially for more fragile patients. This supposition, however, needs to be confirmed in larger and longer studies, the researchers said.
This study was “the first randomized trial to support the non-inferiority of reduced-dose TNFi [inhibitor] doses compared with full doses in patients with SpA,” they wrote.
Reducing treatment dosage to about half was non-inferior for SpA patients, regardless of clinical variables and the type of TNF blockers used. Therefore, a dosage reduction is a viable option for patients in stable clinical remission, the researchers concluded.