Pilot trial: Pioglitazone versus placebo in patients with plaque psoriasis (the P6)

Shafiq, Nusrat; Malhotra, Samir; Pandhi, P; Gupta, Monica; Kumar, Bhushan; Sandhu, Kamaldeep

doi:10.1111/j.1365-4632.2005.02504.x

Cited by 79 publications

(60 citation statements)

References 40 publications

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“…However, their clinical efficacy needs evaluation as PPARb/d agonist, tetradecylthioacetic acid, did not exhibit beneficial effects when applied topically on psoriasis plaques in a pilot study [46]. Shafiq et al [79] in a double-blind clinical trial evaluated 70 patients Arch Dermatol Res with moderate to severe psoriasis who were given placebo, 15 mg/day of pioglitazone or 30 mg/day of pioglitazone. At the end of 10-week trial, PASI scores improved significantly in treated patients with greater benefit in those receiving higher doses of pioglitazone.…”

Section: Psoriasismentioning

confidence: 99%

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Gupta¹,

Mahajan²,

Mehta³

et al. 2015

Arch Dermatol Res

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Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and comprise three different isoforms namely PPARα, PPARγ, and PPARβ/δ with PPARβ/δ being the predominant subtype in human keratinocytes. After binding with specific ligands, PPARs regulate gene expression, cell growth and differentiation, apoptosis, inflammatory responses, and tumorogenesis. PPARs also modulate a wide variety of skin functions including keratinocyte proliferation, epidermal barrier formation, wound healing, melanocyte proliferation, and sebum production. Recent studies have shown the importance of PPARs in the pathogenesis of many dermatological disorders. Clinical trials have suggested possible role of PPAR agonists in the management of various dermatoses ranging from acne vulgaris, psoriasis, hirsutism, and lipodystrophy to cutaneous malignancies including melanoma. This article is intended to be a primer for dermatologists in their understanding of clinical relevance of PPARs and PPAR agonists in dermatology therapeutics.

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Section: Psoriasismentioning

confidence: 99%

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Gupta¹,

Mahajan²,

Mehta³

et al. 2015

Arch Dermatol Res

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“…A striking improvement of skin lesions had initially been documented in patients with psoriasis treated with the oral PPARg activator troglitazone (9,113). Although subsequent clinical trials using the oral PPARg activator rosiglitazone did not substantiate the initial troglitazone observation (114), favorable effects of oral pioglitazone not only on psoriatic skin lesions (10,115) but also on psoriatic arthritis (8) have been reported. An ongoing phase II trial is currently evaluating the efficacy and safety of a combination of pioglitazone with acitretin in psoriasis (NCT00395941: clinicaltrials.gov).…”

Section: Clinical Trials In Humansmentioning

confidence: 99%

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

Schmuth

Jiang

Dubrac

et al. 2008

Journal of Lipid Research

182

160

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The epidermis is a very active site of lipid metabolism, and all peroxisome proliferator-activated receptor (PPAR) and liver X receptor (LXR) isoforms are expressed in the epidermis. Activation of PPARa, -b/d, or -g or LXRs stimulates keratinocyte differentiation. Additionally, activation of these receptors also improves permeability barrier homeostasis by a number of mechanisms, including stimulating epidermal lipid synthesis, increasing lamellar body formation and secretion, and increasing the activity of enzymes required for the extracellular processing of lipids in the stratum corneum, leading to the formation of lamellar membranes that mediate permeability barrier function. The stimulation of keratinocyte differentiation and permeability barrier formation also occurs during fetal development, resulting in accelerated epidermal development. PPAR and LXR activation regulates keratinocyte proliferation and apoptosis, and studies have shown that these receptors play a role in cutaneous carcinogenesis. Lastly, PPAR and LXR activation is anti-inflammatory, reducing inflammation in animal models of allergic and irritant contact dermatitis. Because of their broad profile of beneficial effects on skin homeostasis, PPAR and LXR have great potential to serve as drug targets for common skin diseases such as psoriasis, atopic dermatitis, and skin

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“…14,[16][17][18] Further evidence in support of a role for Thiazolidinediones in the treatment of psoriasis was provided Brauchli et al who found a statistically significant decrease in the risk for the development of psoriasis in long-term users of TZDs compared with nonusers. 19 Considering the fact that the effect of TZDs is largely through inhibition of epidermal cells and Methotrexate by suppression of lymphoid cells, and since psoriasis is a disease of both epidermal and lymphoid cells, there is a strong theoretical possibility that these two agents could act synergistically.…”

Section: Introductionmentioning

confidence: 99%

A study to compare the efficacy of methotrexate alone vs. methotrexate plus pioglitazone in the management of plaque-type psoriasis

Shabeer

Bhandare

Satyanarayana

et al. 2017

Int J Basic Clin Pharmacol

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INTRODUCTIONPsoriasis is one of the common, chronic, inflammatory cutaneous diseases in India.1 It is characterized by aberrant differentiation and hyperproliferation of keratinocytes and inflammatory infiltration of leukocytes, predominantly into the dermis.2 It affects 2% to 3% of the world's population, with chronic plaque-type psoriasis accounting for approximately 90% of the cases. 2Prevalence of psoriasis ranges across population from 0% to 11.8% across different populations. 3,4 In India, most prevalence studies are hospital based. 5Kaur et al study that included 782 patients showed a prevalence of 1.4 % among the total dermatology outpatients. A similar study by Bedi et al. reported 2.8% prevalence among the dermatology OPD cases. Genetic correlation in terms of family history showed wide differences between studies. Bedi reported positive family history of psoriasis in 14% of their patients, while Kaur et al reported the same in only 2% of their patients and found that first degree relatives were affected in 84% of the cases, while second degree relatives only in 12% cases. 6,7 Currently the treatment options include the use of Methotrexate, which is an established standard; systemic drug approved by USFDA for the treatment of psoriasis. It acts mainly by inhibiting immune cells and is shown to be more potent in decreasing the number of lymphocytes than keratinocytes. 9Other available options are cyclosporine and oral retinoids, all of which are associated with severe toxicity and are usually an expensive ordeal in Indian scenario. There is a need for novel treatment approach with a better ABSTRACT Background: Psoriasis is a common skin condition affecting a huge segment of global population. So far, the treatment has been confined to drugs like methotrexate, cyclosporine and oral retinoids which are highly toxic for long term usage and requires a novel drug that is safer. Methods: Cases of plaque type psoriasis are divided into two arms and treated with methotrexate monotherapy in group A and methotrexate plus pioglitazone combination therapy in group B. The outcome of the study is analyzed using PASI score and DLQI scoring systems. Results: Group A and Group B showed significant reduction in the PASI and DLQI scores. Group B was better in terms of efficacy (p<0.05) when compared to Group A. There was no significant difference between the groups in terms of DLQI scoring. Both groups had similar side effect profile. Conclusions: Pioglitazone which acts by sensitizing the cells to insulin poses no risk of hypoglycemia. It is more specific for the treatment of psoriasis as it targets the keratinocytes. Present study suggests a possible role as an adjuvant in the treatment of psoriasis, and could pave way for low dose methotrexate and thereby reducing the potential side effects.

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Pilot trial: Pioglitazone versus placebo in patients with plaque psoriasis (the P6)

Abstract: This is the first report from a controlled trial demonstrating that pioglitazone could be considered as an efficacious and safe agent for the treatment of plaque psoriasis. The optimum dose and duration of pioglitazone therapy remain to be determined.

Cited by 79 publications

References 40 publications

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

A study to compare the efficacy of methotrexate alone vs. methotrexate plus pioglitazone in the management of plaque-type psoriasis

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