Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE)

Abstract

ObjectiveEvaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA.MethodsPatients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52.ResultsAmong 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast’s safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0–24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo).ConclusionsIn biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports.Trial registration numberNCT01925768; Results.

Network Meta-Analysis of Tofacitinib, Biologic Disease-Modifying Antirheumatic Drugs, and Apremilast for the Treatment of Psoriatic Arthritis

“… Trial Total no. of ITT patients Population Treatment arms and doses, ITT patient numbers Duration of follow-up time, wk Reference NCT00534313 170 bDMARD-IR TNFi-IR Abatacept 3 mg/kg IV at Week 0, 2, 4, then q4w (n = 45) Abatacept 10 mg/kg IV at Week 0, 2, 4, then q4w (n = 40) Abatacept 30 mg/kg IV at Week 0, 2, 4, then q4w (n = 43) Placebo IV at Day 1, 15, 29, then q4w (n = 42) 24 Mease, et al (2011) 23 ASTRAEA (NCT01860976) 424 TNFi-naïve, TNFi-IR subpopulation Abatacept 125 mg SC q1w (n = 213) Placebo (n = 211) 24 Mease, et al (2017) 24 ADEPT (NCT00195689) 313 TNFi-naïve Adalimumab 40 mg SC q2w (n = 151) Placebo (n = 162) 12 Mease, et al (2005) 2 NCT00646178 100 TNFi-naïve Adalimumab 40 mg SC q2w (n = 51) Placebo (n = 49) 12 Genovese, et al (2007) 25 ACTIVE (NCT01925768) 209 bDMARD-naïve Apremilast 30 mg BID (n = 110) Placebo (n = 109) 16 Nash, et al (2018) 26 PALACE 1 (NCT01172938) 504 bDMARD-naïve, bDMARD-IR subpopulation (≤10% of total population) Apremilast 20 mg BID (n = 168) Apremilast 30 mg BID (n = 168) Placebo (n = 168) 16 Kavanaugh, et al (2014) 27 PALACE 2 (NCT01212757) 484 bDMARD-naïve, bDMARD-IR subpopulations Apremilast 20 mg BID (n = 163) Apremilast 30 mg BID (n = 162) Placebo (n = 159) 16 Cutolo, et al (2016) 28 PALACE 3 (NCT01212770) 505 bDMARD-naïve, bDMARD-IR subpopulation (≤10% of total population) Apremilast 20 mg BID (n = 169) Apremilast 30 mg BID (n = 167) Placebo (n = 169) 16 Edwards, et al (2016) …”

Apremilast in psoriasis and beyond: Big hopes on a small molecule

“…[ 19 ] ACTIVE trial analyzed the effects of apremilast alone in patients of PsA who had no prior exposure to biologicals but had one csDMARD. [ 20 ] Apremilast (30 mg twice daily) use resulted in improvement of clinical features of psoriatic arthritis in both DMARD exposed and nonexposed patients. Around 30% in both the groups have achieved American College of Rheumatology (ACR) response criteria, ACR20 by week 16 compared to around 15% improvement with placebo.…”

“…[ 16 17 18 19 ] The ACTIVE trial has demonstrated early onset of action (at week 2) and sustained efficacy of apremilast at 52 weeks in biological-naïve patients with PsA. [ 20 ] Enthesitis, dactylitis, physical function, and fatigue were also improved in these trials, and a long-term sustained efficacy was also noted. A recent analysis of the pooled data from PALACE 1-3 trials has demonstrated efficacy of apremilast in improving enthesitis and dactylitis up to 3 years.…”

“…as well as real-world postmarketing surveillance were diarrhea, headache, nausea, nasopharyngitis, and upper respiratory tract infections. [ 8 17 20 23 24 25 ] The rates of these adverse events were more during the initial stages of therapy and most of them self-resolved over time. Other less common side effects were depression, suicidal tendency, and weight loss.…”

Apremilast: target synthetic drug for the treatment of psoriatic arthritis and psoriasis

“…На 24-й нед. все больные из группы ПЛ начинали получать АП [39]. Оценка проявлений ПсА проводилась уже на 2-й нед.…”