Botox Versus Tacrolimus in Psoriasis Vulgaris

Официальное название

Efficacy and Safety of Mesobotox as a Potential New Therapeutic Modality of Psoriasis Vulgaris in Comparison/Combination With Topical Calcineurin Inhibitor

Обзор

Psoriasis is a systemic chronic relapsing immune-mediated disease which often requires a long-term therapy. Psoriasis occurs in around 2-3% of the total global population. In Egypt, the prevalence of psoriasis ranges between 0.19% and 3%. Besides, it could have profound implications on the patients' psychological state and quality of life. It is presented by erythematous, scaly plaques over the preferred sites. The pathogenesis of this highly complex disease is still far from being fully understood. Keratinocytes' hyperproliferation and immune system dysfunctions are well recognized contributors, with numerous treatments targeting these unique immunologic dysfunctions.

Подробное описание

Neurogenic inflammation has been suggested as an etiopathogenic factor of psoriasis. Previous reports revealed an increased concentration of nerve fibers as well as a high level of neuropeptides of cutaneous sensory nerve origin, primarily Substance P and calcitonin gene-related peptide (CGRP).

Some investigators reported improvement of psoriatic plaques after injuries that compromised peripheral nerves. Hence, it was postulated that cutaneous sensory afferent neurons are involved in the etiopathogenesis of psoriasis and may serve as a potential therapeutic target.

Substance P (SP) is a neuropeptide of sensory nerve origin that can influence the immune cell functions and the inflammatory responses in psoriasis. By binding to NK1R on T cells, SP can stimulate Th17 cell differentiation and production of interleukin-17A cytokine (IL-17A). IL-17A is a key effector cytokine in psoriasis, by releasing several pro-inflammatory cytokines, such as TNF alpha, stimulating abnormal keratinocytes' proliferation and promoting angiogenesis.

Topical drug therapy is the cornerstone of the treatment of mild to moderate psoriasis. It offers a direct skin targeting and avoids systemic adverse events. Several topical therapies are currently available for the treatment of psoriasis such as topical steroids, topical vitamin D3 analogues e.g. Calcipotriol, tar, anthraline, topical calcineurin inhibitors and tazarotene.

Tacrolimus, formerly known as FK506, is a macrolide antibiotic possessing immunosuppressive properties. Tacrolimus disrupts the intracellular activation of T-lymphocytes and inhibits the ability of calcineurin to regulate gene transcription. Thus, tacrolimus intervenes at an early stage of T-cell activation, leads to several secondary consequences providing effective and therapeutically efficient results to overcome problems associated with psoriatic skin disease.

Botulinum Toxin-A (BoNT-A) is an injectable neuromodulator produced by Clostridium Botulinum, a Gram-positive bacillus that causes Botulism. The clinical utility of BoNT-A originates from the ability to block muscular contractions by inhibiting neurotransmission between peripheral nerve cells and muscle fibers. Currently, BoNT-A is widely used for multiple aesthetic concerns that can be alleviated by local muscle relaxation, such as upper facial dynamic rhytides .

Botulinum Toxin-A can inhibit the release of neurotransmitters e.g. SP from the sensory motor neurons. SP is an important neuropeptide in the pathophysiological process of cutaneous neurogenic inflammation. Thus, it was hypothesized that BoNT-A can potentially be used for treating several inflammatory skin diseases, including psoriasis.

Вмешательства

• Препарат Botulinum Toxin-A
  Botulinum Toxin-A (BoNT-A) is an injectable neuromodulator produced by Clostridium Botulinum, a Gram-positive bacillus that causes Botulism.
• Препарат Tacrolimus
  topical Calcineurin inhibitor

Первичные конечные точки

• To evaluate the efficacy and safety of Mesobotox for treatment of plaque psoriasis as a monotherapy versus its combination with a topical Calcineurin inhibitor 0.03% ointment and topical Calcineurin inhibitor 0.03% ointment alone. [Срок оценки: 6 months]

Вторичные конечные точки (2)

• To explore the treatment effects on the histopathological features of psoriasis. [Срок оценки: 2 months]
• To explore the treatment effects on the immunohistochemical features of psoriasis. [Срок оценки: 2 months]

Критерии участия

Критерии включения

• Patients with clinical diagnosis of mild to moderate psoriasis vulgaris
• Patients who stopped any systemic therapy or phototherapy for at least 3 months and topical therapy for at least 4 weeks prior to enrollment.

Критерии исключения

• • Psoriasis vulgaris involving > 10% of the body surface area, pustular or erythrodermic psoriasis.

• Patients with neuromuscular disease or history of epilepsy.
• Pregnant or lactating females.
• Patients with any current dermatological disease.
• Patients with any current systemic disease.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. Psoriasis Prevalence in Adults in the United States. JAMA Dermatol. 2021 Aug 1;157(8):940-946. doi: 10.1001/jamadermatol.2021.2007. PMID 34190957
• Omar SS, Helaly HA. Prevalence of ocular findings in a sample of Egyptian patients with psoriasis. Indian J Dermatol Venereol Leprol. 2018 Jan-Feb;84(1):34-38. doi: 10.4103/ijdvl.IJDVL_1239_15. PMID 29067934
• Goff KL, Karimkhani C, Boyers LN, Weinstock MA, Lott JP, Hay RJ, Coffeng LE, Norton SA, Naldi L, Dunnick C, Armstrong AW, Dellavalle RP. The global burden of psoriatic skin disease. Br J Dermatol. 2015 Jun;172(6):1665-1668. doi: 10.1111/bjd.13715. Epub 2015 May 6. No abstract available. PMID 25645671
• Khattab FM, Samir MA. Botulinum toxin type-A versus 5-fluorouracil in the treatment of plaque psoriasis: Comparative study. J Cosmet Dermatol. 2021 Oct;20(10):3128-3132. doi: 10.1111/jocd.14306. Epub 2021 Jul 14. PMID 34146460
• Kubanov AA, Katunina OR, Chikin VV. Expression of Neuropeptides, Neurotrophins, and Neurotransmitters in the Skin of Patients with Atopic Dermatitis and Psoriasis. Bull Exp Biol Med. 2015 Jul;159(3):318-22. doi: 10.1007/s10517-015-2951-4. Epub 2015 Jul 24. PMID 26201903
• Popescu MN, Beiu C, Iliescu MG, Mihai MM, Popa LG, Stanescu AMA, Berteanu M. Botulinum Toxin Use for Modulating Neuroimmune Cutaneous Activity in Psoriasis. Medicina (Kaunas). 2022 Jun 16;58(6):813. doi: 10.3390/medicina58060813. PMID 35744076
• Khattab FM. Evaluation of Botulinum Toxin A as an Optional Treatment for Atopic Dermatitis. J Clin Aesthet Dermatol. 2020 Jul;13(7):32-35. Epub 2020 Jul 1. PMID 32983334
• Gonzalez C, Franco M, Londono A, Valenzuela F. Breaking paradigms in the treatment of psoriasis: Use of botulinum toxin for the treatment of plaque psoriasis. Dermatol Ther. 2020 Nov;33(6):e14319. doi: 10.1111/dth.14319. Epub 2020 Oct 8. PMID 32949180

Идентификаторы

NCT: NCT06203470 · BTP

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗