A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial

Cutolo, Maurizio; Myerson, Gary E.; Fleischmann, Roy; Lioté, Frédéric; Dı́az-González, Federico; Bosch, Filip Van den; Marzo‐Ortega, Helena; Feist, Eugen; Shah, K.; Hu, ChiaChi; Stevens, R.; Põder, Airi

doi:10.3899/jrheum.151376

Cited by 185 publications

(161 citation statements)

References 30 publications

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“…Improved QOL may help motivate patients to maintain treatment over time, which may lead to better disease control. The safety profile of apremilast during the apremilast‐extension phase was consistent with the ESTEEM and PALACE trials 2, 3, 4, 5, 6, 7…”

Section: Discussionsupporting

confidence: 75%

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: Discussionsupporting

confidence: 75%

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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“…The inhibition of PDE4 increases cyclic adenosine monophosphate, downregulates the inflammatory cascade and leads to inhibition of Th1, Th2 and Th17 cytokines. Its clinical efficacy could be demonstrated in phase 3 trials by improving signs and symptoms of PsA as well as physical function [40, 41]. Ustekinumab is a fully human monoclonal immunoglobulin G1 antibody that binds the common p40 subunit of IL-12 and IL-23.…”

Section: Novel Treatment Targetsmentioning

confidence: 99%

An overview of psoriatic arthritis – epidemiology, clinical features, pathophysiology and novel treatment targets

Kerschbaumer

Fenzl²,

Erlacher³

et al. 2016

Wien Klin Wochenschr

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SummaryPsoriatic arthritis is a chronic inflammatory joint disease occurring in a subgroup of patients suffering from psoriasis. This article gives an overview of the complexity of psoriatic arthritis, looking at several aspects of this heterogeneous disease, such as epidemiology, important clinical features and comorbidities as well as current concepts of the pathophysiology and subsequent insights in novel treatment targets.

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“…Its clinical efficacy was observed in both phase II [77,81] and phase III trials (the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy: PALACE 1, 2, and 3) [82,83,84], in which 41% of patients achieved ACR20 (20% improvement in American College of Rheumatology criteria) for apremilast 30 mg twice daily, compared with 18% for the placebo group [81], with clinical improvements generally being sustained for up to Week 104 [82]. Apremilast has also demonstrated beneficial effects in disease-modifying anti-rheumatic drugs (DMARDs)-naïve PsA-affected patients in the phase III trial, named PALACE 4 [85], although its use is not currently approved in this setting in the EU (Table 1).…”

Section: Apremilast In Immune-mediated Inflammatory Disordersmentioning

confidence: 99%

PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue

Spadaccini

D’Alessio

Peyrin–Biroulet

et al. 2017

IJMS

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Background. In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets. The novel Phosphodiesterase 4 (PDE4) inhibitors have been recently introduced as new modulators of intracellular signals and gene transcription for the treatment of IBD. Aim. To discuss and describe the state of the art of this new class of compounds in the IBD field, with particular attention to apremilast. Methods. Published articles selected from PubMed were comprehensively reviewed, with key words including apremilast, inflammatory disease, IBD, psoriasis, psoriatic arthritis, pathogenesis, therapies, and treatment. Results. PDE4 inhibitors generate elevated intracellular levels of cyclic Adenosine Monophosphate (cAMP), that consequently down-regulate the release of pro-inflammatory cytokines in the mucosa of IBD patients. The newly developed apremilast is one of these drugs and has already been approved for the treatment of dermatologic/rheumatologic inflammatory conditions; studies in psoriasis and psoriatic arthritis have in fact demonstrated its clinical activity. However, no clinical trials have yet been published on the use of apremilast in IBD. Conclusion. In light of the similarity of pro-inflammatory signaling pathways across the gut, the skin, and joints, apremilast is likely supposed to show its efficacy also in IBD.

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A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial

Abstract: Apremilast demonstrated clinical improvements in PsA for up to 52 weeks, including signs and symptoms, physical function, and psoriasis. No new safety signals were observed. ClinicalTrials.gov identifier: NCT01212757.

Cited by 185 publications

References 30 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

An overview of psoriatic arthritis – epidemiology, clinical features, pathophysiology and novel treatment targets

PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue

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