Combination Therapy with Apremilast and Biologics for Psoriasis: A Systematic Review

Gyldenløve, Mette; Alinaghi, Farzad; Zachariae, Claus; Skov, Lone; Egeberg, Alexander

doi:10.1007/s40257-022-00703-1

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…eApremilast is sometimes combined with biologics for psoriasis for enhanced benefit. 8 Similarly, this study suggests that concomitant apremilast and dupilumab may be a promising combination for AD patients with an inadequate response to dupilumab. Limitations of this study include the open-label design, small sample size, high drop-out rate and concomitant use of existing AD medications.…”

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confidence: 57%

Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate‐to‐severe atopic dermatitis

Cunningham

Alsukait

Cohen

et al. 2023

Acad Dermatol Venereol

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Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate-to-severe atopic dermatitis Dear Editor, The pathogenesis of atopic dermatitis (AD) is primarily due to overactive type 2 inflammation, 1 but the Th1 and Th17 pathways can also be activated in lesional skin. [2][3][4] Dupilumab, an interleukin (IL)-4 receptor alpha antagonist that blocks IL-4 and IL-13 cytokine signalling, is an FDAapproved treatment that has revolutionized the treatment of AD. 1 Nevertheless, many patients are still not fully controlled on dupilumab combined with topical therapy. Apremilast, an oral phosphodiesterase-4 inhibitor, is FDA approved for psoriasis, psoriatic arthritis and Behcet's disease. Apremilast can block multiple inflammatory mediators, including tumour necrosis factor-alpha, interferon-gamma, IL-2, IL-12, IL-13 and IL-17. 5,6 While apremilast monotherapy in AD was unsuccessful at significantly improving patients at the FDAapproved dose of 30 milligrams (mg) twice daily, a trend toward Eczema Area and Severity Index (EASI) improvement was observed at Week 12. 6 Therefore, we investigated whether apremilast used in combination with dupilumab would give added benefit to patients.This IRB-approved, open-label, prospective phase 2 study evaluated apremilast 30 mg orally twice daily (after 5-day titration) when added to dupilumab 300 mg b for 10 patients with moderate-to-severe AD, classified as an Investigator's Global Assessment (IGA) score of 3 or greater upon beginning dupilumab, that was not adequately controlled at study initiation (IGA 2 or greater). Patients were permitted to continue their current stable topical AD prescription and over-the-counter regimens and had to be on dupilumab for a minimum of 12 weeks prior to enrolment. b The primary endpoint was the proportion of patients who after starting apremilast, achieved an IGA score of 0 (clear) or 1 (almost clear) at Week 16. Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), itch on Numerical Rating Scale (NRS) and EASI were also recorded. An additional 8 weeks of study drug was administered to assess clinical benefit with continued use, up to 24 weeks after the introduction of apremilast.Patient demographics, clinical characteristics and efficacy outcomes are summarized in Table 1. An intention-to-treat analysis was performed using last-observation-carriedforward and included all enrolled patients who received apremilast at Week 0. Two patients reached the primary endpoint of IGA 0 or 1 by Week 16, and by 24 weeks, this increased to 3 patients. At 16 weeks, BSA ≤3% was achieved in 4/10 patients. BSA, DLQI, NRS pruritus and EASI decreased by an average of 4.5 ± 5.2% (mean ± standard deviation, 95% confidence interval [CI] 0.8-8.2), 3.9 ± 3.1 points (95% CI 1.7-6.1), 2.1 ± 1.1 points (95% CI 1.3-2.9) and 3.02 ± 2.8 (95% CI 1.0-5.0), respectively. Mean percent change from baseline BSA, DLQI, NRS pruritus and EASI was −37.6 ± 26.6% (95% CI -56.7 to −18.6), −36.9 ± 54.8% (95% CI -76.3 to 2.3), −45.9 ± 17.8% (95% CI -5...

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confidence: 57%

Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate‐to‐severe atopic dermatitis

Cunningham

Alsukait

Cohen

et al. 2023

Acad Dermatol Venereol

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“…Another alternative for patients with refractory PsA is the combination of apremilast and biological therapy, since apremilast has a good safety profile even in combination ( 33 , 34 ), but the presumed risk of infections is not comparable with the combination of other biological agents. Of note, a controlled clinical trial (AFFINITY) is ongoing to evaluate the efficacy of guselkumab plus golimumab combination treatment in patients with PsA and inadequate response to prior anti-TNF therapies compared with guselkumab monotherapy (NCT05071664, clinicaltrials.gov).…”

Section: Discussionmentioning

confidence: 99%

Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain

Valero-Martínez,

Urgelles,

Sallés

et al. 2023

Front. Immunol.

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Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation.

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“…Overall, PDE-4i may have only a modest benefit in patients who are unable to tolerate treatment with a TNFi, but may not be beneficial in those who experience TNFi treatment failure. Currently, PDE-4i has been added to the treatment regimen for patients with PsA as a way to improve the response to a TNFi or other biologics (84,85).…”

Section: Evidence For Treatment Recommendations In Patients Who Faile...mentioning

confidence: 99%

Expert Perspective: Management of the Psoriatic Arthritis Patient After Failure of One Tumor Necrosis Factor Inhibitor

Leung

Kavanaugh

Ritchlin

2023

Arthritis & Rheumatology

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The index case, a 36-year-old woman, had psoriasis (PsO) on her scalp, arms, legs, and trunk since age 25 years that was inadequately controlled with topical agents. She has a past medical history of treated hypertension and depression. She is an active smoker. Three years prior to our case evaluation, she developed polyarthritis, inflammatory back pain, and plantar fasciitis. Methotrexate (MTX) was added to her treatment regimen, first administered orally then subcutaneously, but the patient stated she could only tolerate 12.5 mg/week due to gastrointestinal and systemic adverse events. The dose of 12.5 mg/week resulted in minimal benefit. In addition, the patient was recently married and reported that pregnancy was being considered, and therefore treatment with MTX was stopped. She then experienced a flare of PsO and arthritis.Physical examination was notable for the presence of moderate-to-severe PsO (12% affected body surface area [BSA]), 6-7 swollen and tender joints, and evidence of mild erosive changes on hand radiographs. Monotherapy with adalimumab 40 mg every other week was initiated. The patient improved during treatment with adalimumab over 10 weeks, with 60-70% improvement in her clinical symptoms overall, but continued to experience mild residual joint pain and signs of PsO (2-4% BSA). Approximately 3 months ago, she noted profound fatigue, 90 minutes of morning stiffness, and diffuse joint pain. She found it difficult to continue her work in retail and reported feeling frustrated, anxious, and depressed. Her skin PsO also worsened and became more bothersome to her. On physical examination, her blood pressure was 140/90 mm Hg, pulse rate was 72 beats per minute, and body mass index was 35 kg/m 2 . She had psoriasiform plaques on her trunk and extremities (8% BSA). Musculoskeletal examination revealed 6 tender and 4 swollen joints, and she had a Disease Activity Index for PsA (DAPSA) score of 29 (a DAPSA score of >28 represents high disease activity). There were multiple tender entheses, most notably in the plantar fasciae, left Achilles tendon, and the left elbow lateral condyle. Pain was elicited in the right sacroiliac (SI) joint on provocative testing, and also at several locations unassociated with entheses.

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Combination Therapy with Apremilast and Biologics for Psoriasis: A Systematic Review

Cited by 8 publications

References 29 publications

Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate‐to‐severe atopic dermatitis

Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate‐to‐severe atopic dermatitis

Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain

Expert Perspective: Management of the Psoriatic Arthritis Patient After Failure of One Tumor Necrosis Factor Inhibitor

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