麻豆传媒

No differences in 6-month efficacy outcomes were observed among patients with psoriatic arthritis (PsA) who were treated with ustekinumab (Stelara) versus tumor necrosis factor (TNF) inhibitors, a prospective observational study found.

At 6 months, the change in clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) scores were -13.7 (95% CI -15.5 to -11.8) for ustekinumab and -14.5 (95% CI -16.2 to -13) for TNF inhibitors, according to Josef S. Smolen, MD, of Medical University of Vienna in Austria, and colleagues.

In addition, the propensity score adjusted odds ratio for achieving cDAPSA low disease activity with ustekinumab versus TNF inhibitors was 0.74 (95% CI 0.53-1.04), confirming a nonsignificant difference, the researchers reported online in .

Numerous treatment options are currently available for the treatment of PsA, including nonsteroidal anti-inflammatory drugs, conventional disease-modifying antirheumatic drugs (DMARDs), biologics, and targeted synthetic DMARDs. Based on the pathogenesis of PsA, agents specifically targeting the interleukin (IL)-12 and IL-23/IL-17 axes also have now been developed, adding to the available options such as the various TNF inhibitors.

Ustekinumab inhibits the p40 subunit on the IL-12 and 23 cytokines, and was shown in two trials to be effective for both skin and joint manifestations of PsA. It was approved for PsA in 2013.

Few real-world data are available comparing the efficacy of the different biologics in PsA, which can differ from what is seen in clinical trials. Therefore, Smolen and colleagues conducted a 6-month trial that enrolled 868 patients from 92 centers throughout Europe during the years 2015 to 2018.

At baseline, participants initiated ustekinumab or any approved TNF inhibitor as first-, second-, or third-line treatment. A propensity score analysis was performed to adjust for between-group differences.

Patients in the ustekinumab group were older than those in the TNF inhibitor group (51.2 vs 48.5 years) and had longer disease duration (7.5 vs 6.2 years). They also more often were on their third-line biologic (20.4% vs 12%).

Moreover, extensive skin involvement (affected body surface area above 10%) was present at baseline in more ustekinumab patients (26.7% vs 14.1%), as were chronic widespread pain and cardiovascular and metabolic comorbidities.

"Based on these baseline characteristics, the ustekinumab group could be regarded as more refractory to treatment than the TNF inhibitor comparison group," Smolen and colleagues noted.

Patients in both groups had high levels of disease activity at baseline, with mean cDAPSA scores of 31 and 29.8 in the ustekinumab and TNF inhibitor groups, respectively.

Low disease activity was defined as a score of 13 or lower on the composite cDAPSA, which reflects tender and swollen joint counts, patient global assessment, and pain, while remission was a score of 4 or less. Minimal disease activity and very low disease activity criteria reflect seven domains: tender and swollen joint counts, enthesitis, Psoriasis Area and Severity Index, Health Assessment Questionnaire score, patient global assessment, and pain. Minimal disease activity was defined as sufficient improvement in five of those domains, while all seven must be met for very low disease activity.

The percentages of patients achieving a state of low disease activity by 6 months in the ustekinumab and TNF inhibitor groups were 49.2% and 54.1%. The numbers were 17.5% and 21.9% for remission, 27% and 31.9% for minimal disease activity, and 8.3% and 9.6% for very low disease activity.

After propensity score matching, the odds ratios for achieving the stringent cDAPSA outcome measures showed comparable effects for ustekinumab versus TNF inhibitor therapy:

• Remission, OR 0.73 (95% CI 0.46-1.15)
• Very low disease activity, OR 0.74 (95% CI 0.42-1.30)
• Minimal disease activity, OR 0.87 (95% CI 0.61-1.25)

Changes in quality of life also were similar in the two groups. On the EuroQol questionnaire, the change from baseline was +8.6 at 6 months in the ustekinumab group and +11.8 in the TNF inhibitor group. In both groups, reaching remission, low disease activity, or minimal disease activity at 6 months "was associated with significant and clinically relevant improvement" on quality-of-life measures, the authors observed.

Adverse events were similar in the two groups. Any adverse event was reported by 17.9% of ustekinumab patients and by 20.9% of TNF inhibitor patients, and a serious adverse event by 3.5% and 1.6%, respectively.

Patients will continue to be followed, and future publications will provide additional long-term data on efficacy and safety, according to the investigators.

A limitation of the study was the potential for confounding by indication.

Comment