Ustekinumab or a tumor necrosis factor inhibitor (TNFi) are better used alone than with methotrexate in the treatment of psoriatic arthritis suggest the results of PsABio (A Study on Assessment of STELARA and Tumor Necrosis Factor Alpha Inhibitor Therapies in Participants With Psoriatic Arthritis), a large, ongoing, prospective observational study.
Dr. Stefan Siebert
The percentages of patients achieving multiple psoriatic arthritis disease activity outcome measures at 6 months were higher if biologic monotherapy was used rather than a biologic in combination with methotrexate.
For example, minimal disease activity (MDA) was achieved by 27.5% of patients taking ustekinumab as monotherapy and by 32.1% of those taking a TNFi alone. When methotrexate was used in combination, the respective percentages of patients achieving MDA were 23.7% and 27.8%.
A similar pattern was seen for very-low disease activity (VLDA), with 9.8% of patients in the ustekinumab monotherapy arm and 12% of those in the TNFi monotherapy arm achieving this target, compared with 5.7% and 5.4% when these drugs were combined with methotrexate.
MDA is defined as meeting five or more cutoffs for seven domains of disease activity, and VLDA for all seven: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area Severity Index 1 or less or body surface area involved 3% or less, 0-1 tender entheseal points, Health Assessment Questionnaire score of 0.5 or less, patient global disease activity visual analog scale score of 20 or lower, and patient pain visual analog scale score of 15 or lower.
Other outcome measures used that showed no advantage of adding methotrexate to these biologics were the Clinical Disease Activity in Psoriatic Arthritis low disease activity and remission scores, the patient acceptable symptoms rate of the 12-item Psoriatic Arthritis Impact of Disease Questionnaire, and improvement in skin involvement.
“Patients were no more likely to achieve lower disease activity or a remission target having received methotrexate than they did just on the biologic drug on its own,” Stefan Siebert, MBBCh, PhD, one of the PsABio investigators, said in an interview.
Dr. Siebert, who is clinical senior lecturer in inflammation and rheumatology at the University of Glasgow (Scotland), was scheduled to present the findings at the British Society for Rheumatology annual conference. The meeting was canceled because of the ongoing COVID-19 crisis. Abstracts and ePosters from the meeting have since been released in a supplement to Rheumatology and via the BSR’s conference app.
First data for ustekinumab
“There certainly doesn’t appear to be any added benefit from using methotrexate on a group level in patients getting ustekinumab and TNF inhibitors,” Dr. Siebert said. “We’ve looked at everything,” he emphasized, and “none of the single domains or composite measures were improved by the addition of methotrexate. I think we knew that for TNF inhibitors, but the key thing is we’ve never known that for ustekinumab, and this is the first study to show that.”
Indeed, the findings match up with those from the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study in which patients who were treated with the TNFi etanercept as monotherapy did much better than those given the TNFi in combination with methotrexate or methotrexate alone. While not a randomized trial, PsABio now shows that the same is true for ustekinumab.
Obviously, there are some clear differences between a clinical trial and an observational study such as PsABio. For one thing, there was no randomization and patients taking methotrexate were presumably doing so for good reason, Dr. Siebert said. Secondly, there was no methotrexate-only arm.
PsABio recruited patients who were starting treatment with either ustekinumab or a new TNFi as first-, second-, or third-line biologic disease-modifying antirheumatic therapy (DMARD). “These are all people starting on a biologic, so they’ve already got severe disease and have failed methotrexate on some level. So everything we’ve done is biologic without methotrexate or biologic with methotrexate,” Dr. Siebert explained. Patients may not have been taking methotrexate for a variety of reasons, such as inefficacy or side effects, so PsABio “doesn’t tell us anything about methotrexate on its own.”