Research Highlights

TARGETED THERAPIES OSTEOARTHRITIS Apremilast reduces Short-term prednisolone improves Behçet oral ulcers hand OA Treatment with apremilast 30 mg twice daily Inflammation is often present in the hand inflammation, determined by MRI and for 12 weeks led to a greater decrease in the joints of patients with hand osteoarthritis ultrasonography, were also decreased. number of oral ulcers and in associated pain (OA), particularly in those with erosive “The effects on pain and function we found for patients with Behçet syndrome than disease, and is linked with pain and disease in this trial exceeded those of all currently treatment with placebo, according to the progression. Targeting this inflammation available treatment options,” notes Kroon. results of a new phase III study. More than half with a short course of glucocorticoid therapy Notably, symptoms returned to pre-treatment of the patients treated with apremilast (53%) could offer pain relief, according to the results levels after the prednisolone was tapered were free of oral ulcers at week 12, compared of the Hand Osteoarthritis Prednisolone over 2 weeks. with 22% in the placebo group, and the Efficacy (HOPE) study. “The results of our study provide benefits of the treatment were apparent The study specifically included patients clinicians with a new short-term treatment as early as week 1. with a flare of painful hand OA and signs option for patients with hand OA who Oral ulcers are an early and frequent mani- of active synovial inflammation, in order report a flare-up of their disease,” Kroon festation of Behçet syndrome, and can have a to target those patients who would benefit says. Whether continued treatment would substantial effect on a patient’s quality of life. most from the anti-inflammatory treatment. have provided additional benefit or could Although a number of agents are available to “More liberal patient inclusion criteria eventually modify the disease course remains treat oral ulcers, including colchicine, topical might have been a reason that previous trials to be determined. In light of the potential or systemic glucocorticoids, TNF inhibitors or (of other anti-inflammatory drugs) in hand complications of prolonged glucocorticoid thalidomide, some patients fail to respond OA produced negative results,” suggests therapy, further studies are needed to to these treatments. Apremilast, an orally corresponding author Féline Kroon. determine the optimal dosage and duration ­available small-molecule phosphodies­ Compared with placebo, 6 weeks of of treatment for inflammatory hand OA. terase 4 (PDE4) inhibitor that is already treatment with oral prednisolone 10 mg Sarah Onuora approved for the treatment of psoriasis and daily substantially reduced finger pain Original article Kroon, F. P. B. et al. Results of a 6-week psoriatic arthritis, is a potential treatment (as measured on a 100 mm visual analogue treatment with 10 mg prednisolone in patients with hand for Behçet syndrome as it modulates several scale) and function (measured by AUSCAN osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial. Lancet 394, 1993–2001 (2019) pro-inflammatory mediators that are upregu- function score and FIHOA score). Signs of lated in the disease (TNF, IL-2, IL-8, IL-17 and IFNγ). The phase III results are consistent with SPONDYLOARTHRITIS those of a previous phase II trial of patients with Behçet syndrome from Turkey and the New positive results for upadacitinib in AS USA, but the current trial included a larger The selective Janus kinase 1 (JAK1) inhibitor As well as the primary endpoint of group of patients (n = 207) from 10 countries across 3 continents. Also notable is that updacitinib, which was approved in 2019 ASAS40 response, the study also met for use in patients with rheumatoid arthritis several secondary endpoints related to patients in the phase III study had failed to (RA), is also showing promise as a treatment disease activity (including partial remission), respond to previous treatment with one or for ankylosing spondylitis (AS). In the SELECT- the degree of functional limitation and more nonbiologic agents. AXIS 1 study, upadacitinib not only improved MRI-detected axial inflammation. Compared with the placebo group, the signs and symptoms of AS, but also reduced Updacitinib was well-tolerated, with a patients in the apremilast group had a greater inflammation in the spine and sacroiliac joints safety profile consistent with that seen in improvement in Behçet’s Disease Quality on MRI. previous studies in RA. Rates of adverse of Life score, and in pain associated with The study follows trials of upadacitinib in events were similar in the treatment and oral ulcers as assessed on a 100-mm visual RA and also encouraging phase II trials of placebo groups and no new safety concerns analogue scale. However, adverse events, other JAK inhibitors in AS. SELECT-AXIS 1 were apparent. including diarrhoea, nausea and headache, enrolled adult patients with active AS who Long-term efficacy and safety data are were more frequent in the apremilast group had not yet been treated with biologic expected to be collected in the ongoing than the placebo group. DMARDs. A dose of 15 mg updacitinib ­extension period of SELECT-AXIS 1. Further As the trial had no active comparator, orally once daily was chosen for evaluation. studies are also needed to evaluate upadacitinib­ further studies are needed to determine how At week 14 of SELECT-AXIS 1, 52% (48 of 93) in patients with AS who have previously the efficacy of apremilast compares with of the patients treated with upadacitinib failed to respond to biologic DMARD ­therapy, that of other agents. Longer follow-up is also achieved an ASAS40 response (indicating as well as in the full spectrum of axial required to determine whether long-term ≥40% improvement from baseline according to spondyloarthritis. administration of apremilast could be safe Assessment of SpondyloArthritis International Sarah Onuora and effective. Society criteria), compared with 26% (24 of 94) of patients who were treated with placebo. Original article van der Heijde, D. et al. Efficacy and Sarah Onuora safety of upadacitinib in patients with active ankylosing Differences between the two groups in ASAS40 spondylitis (SELECT-AXIS 1): a multicentre, randomised, Original article Hatemi, G. et al. Trial of apremilast for double-blind, placebo-controlled, phase 2/3 trial. Lancet 394, oral ulcers in Behçet’s syndrome. N. Engl. J. Med. 381, 1918–1928 response were apparent as early as week 2 2108–2117 (2019) (2019) and sustained through 14 weeks.

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