ULTIMATE: Biologic DMARD affords inflammation control in psoriatic arthritis

Interleukin (IL)-17 inhibition with the biologic disease-modifying antirheumatic drug (DMARD) secukinumab appears to produce a substantial reduction in synovitis in psoriatic arthritis (PsA), in addition to improvements in the signs and symptoms of the disease, according to the results of the phase III ULTIMATE.

“This [inflammation-lowering] effect was observed as early as 1 week after the initiation of treatment and continued to improve at each time point of evaluation until week 12,” as pointed out by an international team of researchers.

“The ultrasound approach also allowed assessment of which aspects of synovitis improved first. Thus, the synovial hypertrophy (SH) component showed the response as early as 1 week and the power Doppler (PD) component as early as 2 weeks after treatment initiation, highlighting a fast onset of efficacy of secukinumab in controlling inflammation in PsA,” they added.

Ultrasound in B-mode combined with PD (PDUS) facilitates visualization of both morphological and functional changes of synovium. As such, the European League Against Rheumatism (EULAR) and the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) standardized the use of PDUS for detecting synovitis and developed a composite scoring system at joint and patient level, named the Global EULAR-OMERACT Synovitis Score (GLOESS). [Reumatol Clin 2018;14:27-35; RMD Open 2017;3:e000428; Ann Rheum Dis 2015;74:1327-1339; Arthritis Rheumatol 2012;64:S352-S353]

In ULTIMATE, the researchers used GLOESS to assess the direct effect of secukinumab on synovitis in 166 PsA patients (mean age 47 years, median disease duration 4 years, 55 percent female). They were randomized to receive either subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis; n=83) or placebo (n=83) weekly for 12 weeks, followed by 4-weekly dosing thereafter until week 52. These patients had clinical synovitis and enthesitis, with an inadequate response to conventional DMARDs, and underwent PDUS evaluation at multiple time points.

Among the patients who completed 12 weeks of treatment (secukinumab, 99 percent; placebo, 95 percent), the primary endpoint of a significant decrease in GLOESS was met. The decrease was greater with secukinumab than with placebo (adjusted mean change in GLOESS, −9 vs −6; difference, −3, 95 percent confidence interval, −6 to −1; p=0.004). [Rheumatology 2021;doi:10.1093/rheumatology/keab628]

Likewise, the American College of Rheumatology (ACR) 20 and 50 responses at week 12 were more favourable among secukinumab-treated patients than those who received placebo, with marked improvements seen as early as week 1 for ACR20 and week 2 for ACR50.

There were no new or unexpected safety findings documented. The most frequent treatment-emergent adverse events (AEs) with either secukinumab or placebo were nasopharyngitis, hypertension, diarrhoea, headache, and latent tuberculosis. None of the patients died or developed serious AEs, serious infections, neutropaenia, major adverse cardiovascular events, inflammatory bowel disease, or malignancies.

“To date, only one small observational study has suggested that DMARDs have an effect on synovitis in PsA… ULTIMATE revealed that the activity of synovitis in PsA can be scored at patient level using a validated ultrasound scoring system. Moreover, the study showed that reliable assessment of synovitis in PsA is feasible across different centres,” the researchers said. [Arthritis Res Ther 2018;20:153]

The team described GLOESS as highly sensitive and reliable, given that it was able to detect a change in synovitis across different ultrasound devices and examiners even without excluding patients with protocol deviations.

“As synovitis is critical for cartilage and bone destruction in PsA, [ULTIMATE] also provide the basis for the observed protection of joint structure by secukinumab in patients with PsA,” they added.