Efficacy of Atorvastatin as Adjunctive Treatment for Chronic Plaque Type Psoriasis

Atorvastatin as Adjunctive Therapy for Chronic Plaque Type Psoriasis Versus Betamethasone Valerate Alone:A Randomized, Double-Blind, Placebo-Controlled Trial

This study aimed to assess the efficacy and safety of atorvastatin 40 mg/day as an adjunct to betamethasone valerate 0.1% ointment applied twice daily in the treatment of patients with mild to moderate chronic plaque type psoriasis, as determined by mean reduction in PASI scores. Specific objectives included the determination and comparison of the absolute number and proportion of patients who achieved PASI-50 and the mean reductions in lipid profile (total cholesterol, HDL, LDL, triglycerides) and high-sensitivity C-reactive protein (hsCRP) measured from baseline and every month thereafter up to 6 months of treatment. This study also investigated the impact of atorvastatin treatment on the patients' quality of life as well as the association of clinical response to the lipid-lowering and anti-inflammatory effects of atorvastatin.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo

Detailed Description

This was a single-center, parallel-group, randomized, double-blind, placebo-controlled clinical trial. The study was conducted from February 2013 to October 2013 at a dermatology out-patient clinic in a tertiary hospital in the Philippines. Twenty-eight patients aged 19-65 years old assessed to have mild to moderate chronic plaque psoriasis, with psoriasis area and severity index (PASI) scores less than 10, were enrolled into the study and randomized into two equal treatment groups. Before participating in the study, patients were required to have a washout period of psoriasis pharmacotherapy for at least 2 months for phototherapy and systemic drugs, and 2 weeks for topical therapies.

Exclusion criteria were as follows: patients with uncontrolled hypertension, endocrine or other metabolic diseases; patients with known allergy to any of the treatments; patients with active liver disease or liver enzymes (AST and ALT) thrice the upper limit; patients with any myopathy or presence of elevated creatine kinase (CK-MM) levels; patients taking any drug that might interact with statins and those already taking statins or patients with clear indications for statin treatment; patients with impaired renal function or creatinine > 2.0 mg/dL; patients with active infection or white blood cell (WBC) > 10 and pregnant or lactating females. The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee. Informed consent was obtained from all participants at study entry.

Patients were randomly assigned into the two groups through a computer-generated randomization table with sequencing of assignments unknown to the primary investigator. The assigned interventions were placed in sequentially-numbered, opaque envelopes, which were opened by one of the secondary investigators only after the patient had agreed to participate in the study. Patients were assigned numerical codes that were indicated in their case record forms.

Fourteen patients took atorvastatin 40 mg once a day while 14 patients took a similar-looking placebo tablet once a day. The study duration was 6 months. All patients were allowed to continue the use of betamethasone valerate 0.1% ointment twice a day for the duration of the study. Dispensing of the medications was done by a secondary investigator, while clinical assessment was done by the primary investigator who was blinded to the treatment assignments.

Patients' PASI scores, lipid profiles, aspartate aminotransferase (AST), alanine aminotransferase (ALT), hsCRP levels, and dermatology life and quality index (DLQI) scores were taken at baseline. Recording of the lipid profile, and AST, ALT values was done by another secondary investigator so that the primary investigator would not be biased by the decreasing values of the lipid profile or elevations in the AST or ALT. Photo-documentation was done throughout the study. Patients were also asked to bring their medications each visit so that the primary investigator could check for compliance. PASI scores, lipid profiles, AST, and ALT levels were monitored monthly, while DLQI scores and hsCRP levels were evaluated again after 6 months of therapy. Difference in the mean changes in PASI scores, lipid profile levels, DLQI scores, and hsCRP levels between groups were compared. Difference in the proportion of patients reaching 50% reduction in PASI scores (PASI-50) after 3 months and that after 6 months of therapy were compared. Correlation between the changes in PASI scores and the changes in lipid profile levels, as well as correlation between the changes in PASI scores and the changes in hsCRP levels were computed.

The period of observation for adverse events started from the time the subject received the first dose of the study drug until his last follow-up. Adverse event monitoring was by active query and spontaneous reporting.

Intention-to-treat analysis was the primary efficacy analysis. Patients included were those who had at least one assessment beyond baseline (Month 1). The last measurement of each randomized patient was moved forward to represent the end-of-treatment measurement at 6 months. Per-protocol analysis was the secondary efficacy analysis. All data analyses were performed using a statistical software (STATA 12.0).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Philippines
  • Manila, Philippines, 1000
    • University of the Philippines - Philippine General Hospital Section of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with mild to moderate psoriasis vulgaris, chronic plaque type, with PASI score not more than 10
• Adult patients ≥ 19 years old and ≤ 65 years old
• Male or female
• Able to give consent
• Able to follow-up monthly for 6 months

Exclusion Criteria:

• Patients with PASI score ≥ 10
• Systemic therapy for psoriasis within the last two months
• Phototherapy within the last four weeks
• Known allergy to any of the treatments
• Active liver disease or liver enzymes (AST and ALT) more than 3 times the upper limit of normal
• Any myopathy or presence of elevated creatine kinase (CK-MM) levels
• Intake of any drug that might affect or interact with the study drug (e.g. fibrates, niacin, macrolide antibiotics)
• Patients already taking statins or patients with clear indications for statin treatment (i.e. coronary heart disease or disease equivalents according to the Adult Treatment Panel III Guidelines)
• Impaired renal function or creatinine > 2.0 mg/dL
• Active infection or WBC > 10
• Pregnant or lactating
• Uncontrolled hypertension, endocrine or other metabolic diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin; Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most	Drug: Atorvastatin; Atorvastatin is a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor used to treat dyslipidemia; Other Names: Atopitar
Placebo Comparator: Placebo; Placebo tablets But patients are still asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most	Drug: Placebo; Placebo tablets, made to look like the interventional drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Gross Change in Psoriasis Area and Severity Index (PASI) Scores From Baseline to the End of 6 Months	Psoriasis Area and Severity Index involves grading psoriatic plaques based on erythema (E), infiltration (I), desquamation (D). Severity is graded from 0-4 for each criteria (0 - none, 1 - slight, 2 - moderate, 3 - severe, and 4 - very severe). The body is divided into 4 regions, head, upper extremities, trunk, and lower extremities, and for each region, the surface area involvement is graded on a 0-6 scale (0 - 0% involvement, 1 - <10%, 2 - 10-<30%, 3 - 30-<50%, 4 - 50-<70%, 5 - 70-<90%, 6 - 90-100%).The highest potential PASI score is 72, with higher PASI scores indicating worse psoriasis.	6 months
Percentage of Patients Achieving PASI-50 in Each Arm at the End of 6 Months	Percentage of patients in each arm who will achieve 50% reduction in PASI scores at the end of 6 months will be compared	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monthly Mean Changes in PASI Scores	PASI scores were measured monthly and mean changes from baseline for each month for the whole 6-month duration of the study recorded.	Monthly from baseline to 6 months
Percentage of Patients Achieving PASI-50 at the End of 3 Months	PASI-50 means at least a 50% reduction from baseline PASI score	3 months
Mean Change in Dermatology Life Quality Index (DLQI) Scores After 6 Months		6 months
Mean Change in Lipid Profile Levels		6 months
Mean Change in hsCRP Levels		6 months
Adverse Events		6 months

Collaborators and Investigators

• Sponsor: Philippine Dermatological Society
• Investigators: Principal Investigator: Sharlene H Chua, Medicine, University of the Philippines-Philippine General Hospital Section of Dermatology; Study Director: Ma. Lorna F Frez, Medicine, University of the Philippines-Philippine General Hospital Section of Dermatology

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: April 28, 2015
• First Posted (Estimate): May 1, 2015

Study Record Updates

• Last Update Posted (Estimate): November 23, 2015
• Last Update Submitted That Met QC Criteria: October 21, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: psoriasis; atorvastatin; chronic plaque psoriasis; psoriasis area and severity index; betamethasone valerate
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: PDS_PGH_2013_002