番茄社区

More patients with oligoarticular psoriatic arthritis (PsA) saw symptoms largely disappear when apremilast (Otezla) was started early in the disease course compared with placebo, a randomized trial showed.

With more than 300 patients in the trial, dubbed FOREMOST, 33.9% of those assigned to apremilast achieved minimal disease activity (MDA) in "sentinel" joints (those affected at baseline) after 16 weeks, compared with 16.0% of the placebo group, according to Laure Gossec, MD, PhD, of Sorbonne Université in Paris, and colleagues.

When assessments were expanded to include all joints, MDA rates were 21.3% with apremilast versus 7.9% with placebo, the researchers .

was the first randomized trial to examine targeted therapy in early oligoarticular PsA, the group noted. The results, they added, "may inform the appropriate management of disease in these patients, but further studies are needed."

As in other rheumatic disorders, clinicians and patients have been eager for ways to shut down or at least minimize PsA symptoms when they first appear. This has been just as true for oligoarticular PsA, in which only a few joints are involved. Up to half of all PsA patients have this less severe version that nevertheless "can significantly impact the quality of life," Gossec and colleagues observed.

Apremilast is an oral phosphodiesterase-4 inhibitor that is already approved for active PsA based on studies in patients with established disease. Neither it nor other targeted agents, however, have been rigorously tested in patients whose symptoms came on within only the past few years.

Gossec and colleagues enrolled 308 patients with at least one swollen and at least one tender joint, but no more than four of either. Disease duration was initially capped at 2 years, but that was later extended to 5 years when recruitment proved to be too slow. Patients on methotrexate or sulfasalazine at enrollment could stay on them during the trial. Corticosteroids and non-steroidal anti-inflammatory drugs could continue as well, so long as patients were on stable doses. An important requirement was that patients had not previously received biologic agents, Janus kinase inhibitors, or three or more old-line anti-rheumatic drugs for their PsA.

MDA -- maximum one swollen and one tender joint -- in sentinel joints when assessed at week 16 served as the primary endpoint. Secondary outcomes included MDA across all joints (i.e., allowing for new involvement of non-sentinel joints), clinical remission, low disease activity (LDA), patients' pain ratings, and patient and physician evaluations of overall response. Remission and LDA were defined by scores on the index: 4 or less as remission, and from 4 to 13 as LDA.

All of these outcomes significantly favored apremilast, although some of the prespecified targets were out of reach for most patients irrespective of treatment. For example, only 29% of those on apremilast gauged their pain at 15 or less on a 100-point scale, versus 13% of the placebo group (P=0.002), and just 30% of the apremilast patients scored their global response at less than 20 out of 100, compared with 19% of the placebo group (P=0.029).

On the other hand, 60% of the apremilast group achieved remission or LDA, whereas this was seen in only 38% of those assigned to placebo (P<0.001). And a less stringent global response endpoint that combined both physician and patient assessments showed that about 60% of the apremilast group had good/moderate responses, versus 40% among those on placebo (P=0.001). Gossec and colleagues noted, too, that 20% of the apremilast group with four or fewer active joints at baseline went on to have more than four at week 16, whereas such progression was seen in 35% of the placebo group.

Safety findings were about as expected. Somewhat more patients on apremilast experienced treatment-emergent adverse events, largely due to increased rates of diarrhea and nausea. Two patients on apremilast died, one halfway through the treatment period and the other 3 months afterward; the investigators decided the deaths were not related to treatment.

Comment