In patients with active ankylosing spondylitis (AS), treatment with oral phosphodiesterase 4 (PDE4) inhibitor apremilast does not confer clinical benefits, with safety and tolerability evaluations consistent with the known profile of apremilast, according to study results published in The Journal of Rheumatology.

In the current study, the investigators sought to evaluate the efficacy and safety of apremilast in patients with active AS.

The phase 3, double-blind, randomized, placebo-controlled study (ClinicalTrials.gov Identifier: NCT01583374) was conducted between May 2012 and October 2018 at 88 sites in North America, Europe, South Africa, and Russia. All adult participants were randomly assigned 1:1:1 to receive placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily for 24 weeks, followed by a long-term extension phase of up to an additional 4.5 years (236 weeks). The primary study endpoint was the percentage of patients who fulfilled the Spondyloarthritis International Society 20 (ASAS 20) response at week 16. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) was used to evaluate the effect of treatment on radiographic outcomes after 104 weeks.


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A total of 490 participants with active AS were randomly assigned to receive treatment, with 164 receiving placebo, 163 receiving apremilast 20 mg twice daily, and 163 receiving apremilast 30 mg twice daily. Results of the study indicated that ASAS 20 response at week 16 was not met with placebo, apremilast 20 mg twice daily, and apremilast 30 mg twice daily (37%, 35%, and 33%, respectively; P =.44 vs placebo). Mean changes from baseline in mSASSS at week 104 were 0.83 (SD, 3.57) in patients who received placebo, 0.98 (SD, 2.18) in those who received apremilast 20 mg twice daily, and 0.57 (SD, 1.86) in those who received apremilast 30 mg twice daily.

Diarrhea, nasopharyngitis, upper respiratory tract infection, nausea, and headache were the most commonly reported adverse events through week 104.

Study limitations included the differences in demographic, disease activity, and radiographic data observed in this analysis vs other comparison studies; the inability to accurately detect effect on radiographic progression due to differences in mSASSS scores; and the inability to measure the effects of cytokine modulation, caused by PDE4 inhibition, on different immune cells.

Researchers speculated that the failure of apremilast to demonstrate efficacy in this patient population was suggestive of a dominant effect of PDE4 inhibition on the proinflammatory cytokine interleukin (IL)-23, which is consistent with the failure of biologic disease-modifying antirheumatic drugs that target the p19 subunit of IL-23 to be effective in this disease phenotype.

Disclosure: This clinical trial was supported by Celgene. Please see the original reference for a full list of authors’ disclosures.

Reference

Taylor PC, van der Heijde D, Landewé R, McCue S, Cheng S, Boonen A. A phase III randomized study of apremilast, an oral phosphodiesterase 4 inhibitor, for active ankylosing spondylitis. J Rheumatol. Published online February 15, 2021. doi:10.3899/jrheum.201088