Aiming for a disease activity target while reducing biologic therapy could be a winning approach for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), according to the results of a new study presented at the annual European Congress of Rheumatology.
The findings show that a treat-to-target (T2T) strategy with tapering using a tumor necrosis factor (TNF) inhibitor produces results that are noninferior to a T2T strategy that doesn’t include tapering in these patients.
Dr. Celia Michielsens
“Our study has for the first time shown that a treat-to-target tapering strategy is just as good as full-dose continuation, while reducing medication use substantially,” first author Celia Michielsens, MD, a PhD student and researcher at Sint Maartenskliniek in Nijmegen, the Netherlands, said in an interview before her presentation of the study during an oral abstract session at the congress. “Stepwise tapering is also better than fixed-dose reduction or discontinuation, since it is much more individualized.”
The study is now published in Annals of the Rheumatic Diseases.
In the randomized, controlled, open-label, noninferiority study, researchers enrolled patients with PsA or axSpA who were using a TNF inhibitor such as etanercept, adalimumab, or infliximab, and had stable low disease activity for at least 6 months. Patients needed to have a Psoriatic Arthritis Disease Activity Score (PASDAS) of 3.2 or less, or an Ankylosing Spondylitis Disease Activity Score (ASDAS) of at 2.1 or less. In cases of flare, patients were treated with NSAIDs and/or glucorticoids, and if they still had not reached low disease activity after a month, their previous TNF inhibitor dose was reinstated to the last effective interval or dosage, which was maintained throughout the study period. When the patient was already using a full TNF-inhibitor dose or if dose adjustment did not suffice, patients were switched to another biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD).
Participants were randomized, from January 2019 to June 2021, to a tapering or a nontapering T2T strategy in a 2:1 fashion. Then researchers then followed them for 12 months and aimed to determine if the tapering strategy proved noninferior to not tapering within a predefined 20% margin for noninferiority, which Dr. Michielsens said was derived from other studies and what her group determined to be “an acceptable risk.”
Results show strategy is ‘feasible in daily clinical care’
A total of 81 patients – 42 with PsA and 39 with axSpA – were in the group with tapering, and 41 were in the group without tapering: 22 with PsA and 19 with axSpA.
At 12 months, researchers found that 69% of the patients in the group with tapering had low disease activity, measured via the PASDAS and ASDAS, compared with 73% in patients who did not taper. And those in the tapering group saw their medication use dramatically reduced. At the 12-month mark, they were taking just 53% of the defined daily dose for maintenance, compared with 91% of the defined daily dose for the group that didn’t taper.
The researchers were able to successfully taper 72% of the patients in the tapering group, with 28% of them discontinuing their TNF-inhibitor medication entirely. The incidence of flares was 85% in the tapering group and 78% in the nontapering group, a nonsignificant difference (P = .32).
The start of a new medication or an increase in use of an existing medication was more frequent in the tapering group, and significantly so for NSAIDs. An increase in NSAID use was seen in 54% of the tapering group and in just 24% of the nontapering group (P = .002).
Conventional synthetic DMARD use went up in the tapering group, compared with the nontapering group, but this was only among the PsA patients and the change in use was not statistically significant. There were also more frequent increases in glucocorticoid use in the tapering group, compared with the nontapering group, but this was not significant.
Dr. Michielsens said the findings show the value of an individualized approach in treating patients with PsA or axSpA.
“Our study – and those [studies] in rheumatoid arthritis earlier – deliver the highest quality of evidence that disease activity–guided dose personalization can, and in fact should, be used in clinical practice,” she said. “Our pragmatic treat-to-target tapering strategy is feasible in daily clinical care, although treat-to-target using PASDAS and ASDAS needs some implementation. In shared decision-making with patients, a 50% reduction in TNFi use is obtainable, while maintaining low disease activity.”
The increase in the use of NSAIDs is something to be aware of, but it is “not concerning,” Dr. Michielsens added. She pointed out that the NSAID use was typically temporary, used when flares arose, and that the drugs are effective, safe, and inexpensive. She also noted that the use of TNF blockers decreased more than the use of NSAIDs increased.
“This seems a perfectly acceptable trade-off that can be discussed with your patient,” she said.
The 12-month duration of the study is likely long enough to show that the tapering strategy works, Dr. Michielsens said. In rheumatoid arthritis studies, for example, differences in strategies didn’t change after 1 year.
“That said, we are doing an observational extension study to provide more insights in the long-term effects of this treat-to-target strategy,” she said. “At the end of this summer, all patients will have completed their extended follow-up period – a 12-month observational period – so hopefully we can present the results next year at EULAR.”
This study received funding from ReumaNederland. Dr. Michielsens did not have any financial interests to disclose. Two coauthors reported financial relationships with numerous pharmaceutical companies.