Background/Purpose: Psoriatic arthritis (PsA) is associated with obesity and increased cardiometabolic risk. Weight loss has been noted in association with the phosphodiesterase 4 (PDE4) inhibitor apremilast.  Studies also suggest a potential role for PDE4 in glucose metabolism.  We aimed to investigate the effects of PDE4 inhibition with apremilast on metabolic and vascular status in PsA.

Methods: The Immune Metabolic Associations in Psoriatic Arthritis (IMAPA) study was a prospective, open label study of adults receiving apremilast as part of routine care for PsA and/or psoriasis.  Cardiometabolic, anthropometric, and disease activity assessments were performed at baseline, months 1, 3, and 6 of apremilast treatment in 60 patients.  A subgroup underwent endothelial function assessment by Endo-PAT (n=38) and MRI of abdominal fat distribution (n=25) at baseline and 3 months of apremilast treatment.  The primary endpoints were change in body weight and glucose homeostasis parameters after 3 months of PDE4 inhibition with apremilast.  Secondary outcomes included change in lipid profile, blood pressure, endothelial function, visceral, subcutaneous, and liver fat percentage on MRI.  Repeated measures mixed models were used to compare mean changes in outcomes.

Results: 60 participants were recruited; median age (IQR) 55 (43, 62) years, 63% female, median disease duration (IQR) 8.0 (2.0, 12.2) years.  To date, outcome data available for n=59 at baseline, n=54 month 1, n=49 month 3, and n=43 month 6.  Results are summarised in table 1.   Mean weight loss after 3 and 6 months apremilast treatment was -1.4kg (95% CI -2.1, -0.6, p=0.001) and -2.2kg (95% CI -3.1, -1.4, p< 0.001), respectively.  >5% weight loss was achieved in 6.1% (3/49) and 21.4% (9/42) after 3 and 6 months treatment, respectively.  There was no statistically significant change in HbA1c, fasting, 1 hour and 2 hour glucose and insulin concentrations, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and area under the OGTT curve for glucose or insulin after 3 months treatment.  Small reductions in total cholesterol, HDL-C, and LDL-C were seen at 3 months.  Mean systolic BP decreased by 4.7mmHg after 6 months, however this was no longer statistically significant after excluding antihypertensive use.  There was no statistically significant change in Reactive Hyperemia Index (RHI).  Median liver fat fraction was 8.12% (IQR 4.00-13.89) at baseline.  There was a modest reduction in abdominal subcutaneous adipose tissue (ASAT), with no change in visceral adipose tissue or liver fat fraction after 3 months treatment.   Statistically significant improvements in 66/68 joint count, DAS28-ESR, PtGA, PGA, pain-VAS, LEI, and PASI were seen at month 6.  These were independent of weight changes.

Conclusion: Apremilast was associated with modest weight loss and reduced disease activity over 6 months.  There was no statistically significant change in glucose parameters or endothelial function, although there was minimal glycaemic and vascular dysfunction at baseline.  Apremilast was associated with reduced total cholesterol, LDL-C, and HDL-C and modest reductions in ASAT at 3 months.  Improvements in disease activity with apremilast appear largely independent of weight change in this cohort.

ACR abstract_IMAPA_table1

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-phosphodiesterase-4-inhibition-with-apremilast-on-cardiometabolic-outcomes-in-psoriatic-arthritis-initial-results-from-the-immune-metabolic-associations-in-psoriatic-arthritis-ima/