The efficacy and safety of apremilast, etanercept and placebo in patients with moderate‐to‐severe plaque psoriasis: 52‐week results from a phase IIIb, randomized, placebo‐controlled trial (LIBERATE)

Reich, Kristian; Gooderham, Melinda; Green, L.; Bewley, Anthony; Zhang, Z.; Khanskaya, Irina; Day, Robert M.; Gonçalves, Joana; Shah, K.; Piguet, Vincent; Soung, Jennifer

doi:10.1111/jdv.14015

Cited by 174 publications

(206 citation statements)

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“…In patients who continued or were switched from placebo or etanercept to apremilast during the apremilast‐extension phase, PASI‐75 response rate was maintained across treatment groups at Week 52 (range, 52.7%–57.0%)1 and Week 104 (45.9%–51.9%; Table 1; Fig. 1) and was similar between treatment groups.…”

Section: Resultsmentioning

confidence: 78%

“…At Week 16, mean percentage improvement in PASI score was significantly greater with apremilast compared with placebo ( P < 0.0001). Mean percentage improvement in PASI score was maintained across treatment groups at Week 52 (range, 66.2%–75.1%)1 and continued through Week 104 (63.3%–70.1%; Table 1). Likewise, achievement of sPGA response was significantly greater with apremilast vs. placebo at Week 16 (21.7% vs. 3.6%, P = 0.0005)1; achievement was 24.3%–35.6% across treatment groups at Week 521 and 18.9%–27.4% at Week 104 (Table 1).…”

Section: Resultsmentioning

confidence: 93%

“…2a and 2b). Improvements were maintained at Week 521 and Week 104 in patients who continued or were switched to apremilast during the apremilast‐extension phase. Mean change from baseline in pruritus VAS score across treatment groups was −31.7 to −35.9 mm at Week 521 and −24.4 to −32.3 mm at Week 104 (Table 1).…”

Section: Resultsmentioning

confidence: 95%

“…The most common reasons for withdrawal from the apremilast‐extension phase were lack of efficacy ( n = 27, 11.9%), lost to follow‐up ( n = 25, 11.0%) and withdrawal by patient ( n = 24, 10.6%). Baseline characteristics were balanced between groups 1. Mean psoriasis duration was 18.2 years, and mean PASI score was 19.6 1…”

Section: Resultsmentioning

confidence: 99%

“…LIBERATE (NCT01690299), a global phase 3b study in biologic‐naive patients with moderate to severe plaque psoriasis, demonstrated that significantly more patients receiving apremilast for 16 weeks achieved PASI‐75 (≥75% reduction from baseline in Psoriasis Area and Severity Index [PASI]) vs. placebo 1. A post hoc analysis found no significant difference in response rates among patients given apremilast vs. etanercept, an anti‐tumour necrosis factor‐α biologic agent 1…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study

Reich

Gooderham

Bewley

et al. 2018

Acad Dermatol Venereol

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BackgroundApremilast, an oral phosphodiesterase‐4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis.ObjectiveTo evaluate long‐term efficacy and safety of apremilast in biologic‐naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial.MethodsTwo hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0–72), Scalp Physician Global Assessment (ScPGA; 0–5) and Nail Psoriasis Severity Index (NAPSI; 0–8); patient‐reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0–32) and pruritus visual analog scale (VAS; 0–100 mm).ResultsThe apremilast‐extension phase (Weeks 16–104) included 226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74) and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last‐observation‐carried‐forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%–59.2% of patients; NAPSI mean change from baseline was −48.1% to −51.1%; DLQI score ≤5 was achieved by 66.0%–72.5% of patients; and pruritus VAS mean change from baseline was −24.4 to −32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged apremilast exposure.ConclusionsApremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of apremilast.

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Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study

Reich

Gooderham

Bewley

et al. 2018

Acad Dermatol Venereol

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Risk of Serious Infection in Patients Receiving Systemic Medications for the Treatment of Psoriasis

et al. 2019

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IMPORTANCE There is a need for better understanding of the comparative safety of systemic medications used in the treatment of psoriasis. OBJECTIVE To compare the risk of serious infection associated with biologic and nonbiologic systemic medications in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS An observational cohort study was conducted using medical and outpatient pharmacy claims from 2 large US health insurance claims databases from January 1, 2003, through September 30, 2015. We included patients with a diagnosis of psoriasis who were new users of systemic medications for psoriasis. EXPOSURES Prescription claims for acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, or ustekinumab. MAIN OUTCOMES AND MEASURES The primary outcome was serious infection, defined by inpatient discharge diagnosis International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Cox proportional hazards regression was used to compare rates of serious infection for each exposure (acitretin, adalimumab, apremilast, etanercept, infliximab, and ustekinumab) with the referent group (methotrexate). We used pairwise 1:1 propensity score (PS) matching to adjust for potential confounders, which were assessed during a 180-day baseline period prior to study drug initiation. Results from the 2 databases were pooled via fixed-effects analysis. RESULTS The databases included 31 595 patients in the Optum Clinformatics Data Mart and 76 112 patients in Truven MarketScan who were new users of acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, and ustekinumab. Users of acitretin, apremilast, infliximab, and methotrexate were older and had higher baseline comorbidity scores than subcutaneous biologic users (adalimumab, etanercept, and ustekinumab). The pooled PS-matched analysis yielded a decreased rate of overall serious infection in users of apremilast (hazard ratio [HR], 0.50; 95% CI, 0.26-0.94), etanercept (HR, 0.75; 95% CI, 0.61-0.93), and ustekinumab (HR, 0.65; 95% CI, 0.47-0.89) compared with methotrexate. We did not find a different rate of overall serious infection among users of acitretin, adalimumab, and infliximab compared with methotrexate. Subanalysis by type of serious infection showed a significantly increased risk of cellulitis among users of acitretin compared with methotrexate (PS-adjusted HR, 1.76; 95% CI, 1.11-2.80). CONCLUSIONS AND RELEVANCE Among patients with psoriasis treated with systemic medications in 2 large US claims databases, new users of apremilast, etanercept, and ustekinumab had a decreased rate of serious infection compared with methotrexate.

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Comparison of Biologics and Oral Treatments for Plaque Psoriasis

et al. 2020

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The clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments.OBJECTIVE To estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis.DATA SOURCES A systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included.STUDY SELECTION Phase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline.DATA EXTRACTION AND SYNTHESIS Data were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis. PASI 75,90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline. MAIN OUTCOMES AND MEASURES RESULTSSixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses. CONCLUSIONS AND RELEVANCEThis study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.

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The efficacy and safety of apremilast, etanercept and placebo in patients with moderate‐to‐severe plaque psoriasis: 52‐week results from a phase IIIb, randomized, placebo‐controlled trial (LIBERATE)

Cited by 174 publications

References 18 publications

Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study

Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study

Risk of Serious Infection in Patients Receiving Systemic Medications for the Treatment of Psoriasis

Comparison of Biologics and Oral Treatments for Plaque Psoriasis

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