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\shorttitle{}

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\title{\NormalBaseline\raggedright\bfseries Adapalene Gel Therapy in Patients with Moderate to Severe Acne Vulgaris}
  
      	\def\AuAffLabelStyle#1{\textsuperscript{\upshape#1}}
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\renewcommand\thanks[1]{\begingroup\let\rlap\relax\origthanks{#1}\endgroup}
\author{\hskip2pc\parbox{.82\linewidth}{\AuFont Likitha A \AuAffLabelStyle{1}\thanks{Corresponding author.}\thanks{E-mail: adigopulalikitha@gmail.com}\AuSep 
        Prapurna Chandra Y \AuAffLabelStyle{2}\AuSep 
        Penabaka Venugopalaiah \AuAffLabelStyle{3}\AuSep 
        Yerikala Ramesh \AuAffLabelStyle{3}
      \\[3pt] 
    % Address
    \normalfont\itshape\NormalBaseline \AuAffLabelStyle{1} 
    Ratnam Institute of Pharmacy, Pidathapolur Village and Post, Muthukur (M), SPSR Nellore, Andhra Pradesh 524346\unskip, \normalfont\itshape\NormalBaseline 
    Tel.:~+91 8790013482\AffSep
    \normalfont\itshape\NormalBaseline \AuAffLabelStyle{2} 
    Department of Pharmacology, Ratnam Institute of Pharmacy, Pidathapolur Village and Post, Muthukur (M), SPSR Nellore, Andhra Pradesh 524346\normalfont\itshape\NormalBaseline \AffSep
    \normalfont\itshape\NormalBaseline \AuAffLabelStyle{3} 
    Department of Pharmaceutics, Ratnam Institute of Pharmacy, Pidathapolur Village and Post, Muthukur (M), SPSR Nellore, Andhra Pradesh 524346\normalfont\itshape\NormalBaseline }}
    
    
\maketitle 
\pagestyle{custom}


\begin{abstract}
Acne is  a  chronic inflammatory disease of pilosebaceous  units. Topical  Adapalene is the most effective  despite the availability of various treatments. Abnormalities in plasma lipids are recognized side effects of  Adapalene therapy. Minimal reports compare the lipid changes in intermittent and continuous Adapalene treatment. To evaluate the alteration in  lipid  profile before,  during, and after constant/ intermittent  topical Adapalene therapy. One hundred  patients  with moderate to severe acne  were randomly assigned to two  treatment regimens. Serum levels of lipids  were measured at baseline,  4wk,  8wk,  12wk,  16wk, and at the end of the treatment. A significant increase in cholesterol, triglyceride, and LDL concentration and a decrease in  HDL  levels in a continuous regimen beyond the normal range but not requiring any treatment interruption  compared to intermittent therapy. In intermittent therapy, the cholesterol, triglyceride, and LDL concentration increase was within the normal range. Intermittent  Adapalene therapy  was clinically equally effective, with lesser effects on serum lipid levels and cost than continuous Adapalene therapy.
\end{abstract}
% Keywords:
    
    \noindent\textbf{Keywords:} Acne Vulgaris, Adapalene, Intermittent, Serum Lipids
    %\end of Keywords
        
    
\section{Introduction}
Acne vulgaris is a long-lasting, inflammatory condition of the pilosebaceous unit that causes comedones, papules, pustules, nodules, and cysts, as well as scars in seborrheic areas like the face, back, and chest \unskip~\cite{2072361:29027837}. Almost everyone experiences some degree of acne during adolescence, which resolves on its own in early adulthood \unskip~\cite{2072361:29027838}. Sometimes, the illness continues into the fourth decade or even lasts the rest of one's life. Acne is a significant psychological issue for many teenagers and young adults due to the involvement of the face with cosmetic substantial problems. Acne vulgaris medication does not cure the condition \unskip~\cite{2072361:29027839}. The goal is to lessen pain from inflammatory lesions, enhance the physical appearance, and avoid scarring. The long-term treatment for acne calls for patience \unskip~\cite{2072361:29027840}. The patient needs to be told about the problem. Adapalene controls keratinization and has anti-inflammatory effects, according to in vitro tests. The medication specifically impacts only the b and g subtypes of the nuclear retinoic acid receptors (RARs). Contrarily, the first-generation retinoid, tretinoin, binds to the cytosolic retinoic acid binding protein (CRABP) and all RARs. Adapalene's selective binding to RARs helps explain why it is less likely to irritate patients and more well-liked by them\unskip~\cite{2072361:29027841}. Adapalene is far more stable than tretinoin, even when exposed to light and powerful oxidizers like benzoyl peroxide. After being applied to the skin, Adapalene has been shown to permeate the sebaceous follicle in about five minutes. Adaferin {\textregistered} gel is a specially formulated medication that is proven to penetrate follicular ducts. It contains micro crystals of Adapalene that are equally disseminated and range in size from 3 to 10 mm \unskip~\cite{2072361:29027843}.
    
\section{Materials and Methods}
\textbf{Source of data}

Subjects who, based on the Indian Acne Grading system, have moderate to severe acne in the Department of Dermatology and Venereal Diseases at Government Medical College, Nellore, were selected.

The subjects were between the ages of 15-45 yrs. A written consent was obtained from them before enrolment, and the study details were thoroughly given to them before enrolment. The study was initiated after thorough scrutiny and processing by the Ethics Committee from the Department of Dermatology and Venereal Diseases at Government Medical College, Nellore.

The selected subjects were interviewed, and a questionnaire about the age, sex, weight, and personal and family history of acne vulgaris was handed over to them before the sample was taken in the patient's native tongue. Subject permission, as well as parental consent, were required for minors. 

\textbf{Study design}

A Randomized controlled trial was performed. 

\textbf{Sample size}

A total of 100 subjects with moderate to severe acne vulgaris are randomly assigned to one of the two treatment regimen groups:

Arm 1: 0.1\% Adapalene gel applied once daily for four months (continuous regimen)

Arm 2: 0.1\% gel was applied once daily for one week a month, followed by the study duration of 4 months (intermittent therapy).

\textbf{Sampling method}

Simple random sampling 

Randomization of subjects was done in a 1:1 ratio, containing 50 in each group. They are either to receive intermittent therapy or on a continuous regimen.

Baseline data of subjects was obtained by investigating total cholesterol, Triglyceride, HDL, and LDL before starting topical Adapalene therapy (day), and follow-up investigations were carried out at the end of the 4\ensuremath{^{th}},8\ensuremath{^{th}}, 12\ensuremath{^{th}} week, and the completion of the treatment. The response to treatment and lipid profile were evaluated at the end of every month for four months.

\textbf{Method of collection of data}

\textbf{Inclusion criteria}


  
  \begin{enumerate}
  \item \relax A male with a clinical diagnosis of acne vulgaris, who is not pregnant or lactating, and who is willing to receive adapalene therapy.
  \item \relax {\textgreater} 25 noninflammatory lesions (open and closed comedones), more than 20 inflammatory lesions (papules and pustules), less than one nodular lesion, and no cystic lesions on the face (Global Assessment (IGA) of acne severity Grade 2, 3, or 4).
  \item \relax Willing to forego using any additional topical antibiotics or acne drugs for the 12-week therapy period.
  \item \relax d. If the subject is a female of childbearing potential, they must start treatment during a regular menstrual cycle, have a negative pregnancy test result within two weeks of starting treatment, and be willing to use an acceptable method of birth control throughout the study.
  \item \relax Subjects willing to give permission and consent:
  \end{enumerate}
  
\begin{table*}[!htbp]
\caption{{IGA Scale for Acne Vulgaris} }
\label{tw-45ccb02f6584}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.26740000000000006\linewidth-2\tabcolsep}p{\dimexpr.7325999999999999\linewidth-2\tabcolsep}}
\tbltoprule Grade & Description\\
\tblmidrule 
0 &
  clear skin with no inflammatory lesions or none at all\\
1 &
  The area is nearly transparent and unusual, with only one little inflammatory lesion.\\
2 &
  Papules/pastures only; no nodular lesions; mild severity greater than Grade 1; some no inflammatory lesions; no more than a few.\\
3 &
  More than a tiny modular lesion, moderate severity larger than Grade 2, up to many no-inflammatory lesions, and possibly some inflammatory lesions.\\
4 &
  Severe; larger than Grade 3 up to several noninflammatory lesions, may have inflammatory lesions, however not more significant than a few nodular lesions\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Distribution of 100 acne cases based on age of the patient} }
\label{tw-b4f447d5c781}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3904\linewidth-2\tabcolsep}p{\dimexpr.6096\linewidth-2\tabcolsep}}
\tbltoprule Age & Number of Cases\\
\tblmidrule 
15-24 &
  84\\
25-34 &
  20\\
35-45 &
  4\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Cases are distributed according to sex} }
\label{tw-09dbbf277eaf}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.31389999999999997\linewidth-2\tabcolsep}p{\dimexpr.6861\linewidth-2\tabcolsep}}
\tbltoprule GENDER & NUMBER OF CASES\\
\tblmidrule 
Male &
  60\\
Female &
  45\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Site of acne} }
\label{tw-61a70dfbb2b4}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.50660000000000004\linewidth-2\tabcolsep}p{\dimexpr.49339999999999996\linewidth-2\tabcolsep}}
\tbltoprule Anatomical site of acne & Number of cases\\
\tblmidrule 
Facial acne &
  85\\
Truncal &
  6\\
Both &
  15\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Previous treatment} }
\label{tw-78d7bef651e2}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.4834\linewidth-2\tabcolsep}p{\dimexpr.5166\linewidth-2\tabcolsep}}
\tbltoprule Previous treatment & Number  of patients\\
\tblmidrule 
Antibiotics+Topical &
  42\\
Antibiotics &
  34\\
Topical therapy &
  15\\
Isotretinoin &
  6\\
Adapalene &
  2\\
No treatment &
  20\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Grade of acne} }
\label{tw-be514cf5313b}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2106\linewidth-2\tabcolsep}p{\dimexpr.1894\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule Grade  of  Acne & Week  0 & Week  4 & Week  12 & \\
\tblmidrule 
0 &
  ----------- &
  ------------ &
  10\% &
  10\%\\
I &
  --------------- &
  15\% &
  85\% &
  96\%\\
II &
  65\% &
  69\% &
  16\% &
  4\%\\
III &
  45\% &
  30\% &
  ------------- &
  ---------\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Lipid profile before and after four months of intermittent Adapalene treatment} }
\label{tw-3dc2f392c1e8}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2434\linewidth-2\tabcolsep}p{\dimexpr.2566\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}}
\tbltoprule Lipid & Baseline & After treatment & p-value\\
\tblmidrule 
Cholesterol &
  133.35\ensuremath{\pm} 34.12 &
  155.56\ensuremath{\pm}22.68 &
  \textless\ 0.0001\\
Triglyceride &
  99.59\ensuremath{\pm}45.08 &
  125.88\ensuremath{\pm}41.27 &
  \textless\ 0.0001\\
HDL &
  48.28\ensuremath{\pm}15.40 &
  45.46\ensuremath{\pm}13.08 &
  \textless\ 0.0001\\
LDL &
  60.65\ensuremath{\pm}30.45 &
  85.82\ensuremath{\pm}26.12 &
  \textless\ 0.0001\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Lipid profile before and after four months of continuous Adapalene treatment} }
\label{tw-6ff1d4dae56b}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.22680000000000003\linewidth-2\tabcolsep}p{\dimexpr.2865\linewidth-2\tabcolsep}p{\dimexpr.25659999999999997\linewidth-2\tabcolsep}p{\dimexpr.2301\linewidth-2\tabcolsep}}
\tbltoprule Lipid & Baseline & After treatment & p-value\\
\tblmidrule 
Cholesterol &
  116.54\ensuremath{\pm} 25.09 &
  212.56\ensuremath{\pm}15.55 &
  \textless\ 0.0001\\
Triglyceride &
  98.56\ensuremath{\pm}24.05 &
  192.87\ensuremath{\pm}16.23 &
  \textless\ 0.0001\\
HDL &
  44.67\ensuremath{\pm}11.34 &
  43.99\ensuremath{\pm}8.92 &
  \textless\ 0.0001\\
LDL &
  58.62\ensuremath{\pm}26.33 &
  134.65\ensuremath{\pm}25.04 &
  \textless\ 0.0001\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Comparison of Total cholesterol between Intermittent and Continuous Treatment} }
\label{tw-f6319e7f610a}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2434\linewidth-2\tabcolsep}p{\dimexpr.2566\linewidth-2\tabcolsep}p{\dimexpr.2766\linewidth-2\tabcolsep}p{\dimexpr.2234\linewidth-2\tabcolsep}}
\tbltoprule Period & Intermittent therapy & Continuous therapy & P value\\
\tblmidrule 
Baseline &
  126.35\ensuremath{\pm}35.09 &
  115.55\ensuremath{\pm}25.09 &
  \textless\ 0.450\\
After  four  weeks &
  128.75\ensuremath{\pm}35.46 &
  136.85\ensuremath{\pm}28.53 &
  \textless\ 0.142\\
After  eight  weeks &
  132.79\ensuremath{\pm}32.95 &
  157.85\ensuremath{\pm}26.22 &
  \textless\ 0.0001\\
After  12  weeks &
  138.87\ensuremath{\pm}34.46 &
  178.15\ensuremath{\pm}27.78 &
  \textless\ 0.0001\\
After  16  weeks &
  145.62\ensuremath{\pm}30.72 &
  195.25\ensuremath{\pm}28.78 &
  \textless\ 0.0001\\
After  20  weeks &
  156.58\ensuremath{\pm}25.70 &
  210.56\ensuremath{\pm}16.57 &
  \textless\ 0.0001\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Comparison of Triglycerides between Intermittent and Continuous Treatment triglycerides} }
\label{tw-09dc6613b055}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2434\linewidth-2\tabcolsep}p{\dimexpr.26990000000000002\linewidth-2\tabcolsep}p{\dimexpr.26\linewidth-2\tabcolsep}p{\dimexpr.2267\linewidth-2\tabcolsep}}
\tbltoprule Period & Intermittent therapy & Continuous therapy & P value\\
\tblmidrule 
Baseline &
  98.59\ensuremath{\pm}45.02 &
  98.57\ensuremath{\pm}24.01 &
  \textless\ 0.785\\
After  4   weeks &
  98.49\ensuremath{\pm}45.95 &
  115.50\ensuremath{\pm}24.65 &
  \textless\ 0.0440\\
After  8   weeks &
  105.48\ensuremath{\pm}45.08 &
  132.09\ensuremath{\pm}22.91 &
  \textless\ 0.0002\\
After  12  weeks &
  108.50\ensuremath{\pm}43.79 &
  150.52\ensuremath{\pm}20.20 &
  \textless\ 0.0001\\
After  16  weeks &
  115.26\ensuremath{\pm}45.99 &
  165.25\ensuremath{\pm}18.82 &
  \textless\ 0.0001\\
After  20  weeks &
  126.90\ensuremath{\pm}42.25 &
  188.90\ensuremath{\pm}16.25 &
  \textless\ 0.0001\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Comparison of HDL between Intermittent and Continuous Treatment} }
\label{tw-5fe258fe371d}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2334\linewidth-2\tabcolsep}p{\dimexpr.28990000000000002\linewidth-2\tabcolsep}p{\dimexpr.2466\linewidth-2\tabcolsep}p{\dimexpr.2301\linewidth-2\tabcolsep}}
\tbltoprule Period & Intermittent therapy & Continuous therapy & P value\\
\tblmidrule 
Baseline &
  50.26\ensuremath{\pm}11.38 &
  44.64\ensuremath{\pm}10.32 &
  \textless\ 0.0865\\
After  four  weeks &
  50.48\ensuremath{\pm}12.69 &
  43.86\ensuremath{\pm}9.20 &
  \textless\ 0.0176\\
After  eight  weeks &
  49.63\ensuremath{\pm}13.95 &
  45.00\ensuremath{\pm}11.28 &
  \textless\ 0.0662\\
After  12  weeks &
  51.08\ensuremath{\pm}12.60 &
  41.80\ensuremath{\pm}9.59 &
  \textless\ 0.0054\\
After  16  weeks &
  49.62\ensuremath{\pm}12.99 &
  41.42\ensuremath{\pm}8.56 &
  \textless\ 0.0029\\
After  20  weeks &
  48.45\ensuremath{\pm}10.09 &
  40.98\ensuremath{\pm}7.91 &
  \textless\ 0.0085\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{{Comparison of LDL between Intermittent and Continuous Treatment} }
\label{tw-d28172bf75b4}
\def\arraystretch{1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2367\linewidth-2\tabcolsep}p{\dimexpr.2633\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}}
\tbltoprule Period & Intermittent therapy & Continuous therapy & P value\\
\tblmidrule 
Baseline &
  59.62 \ensuremath{\pm} 32.45 &
  60.62 \ensuremath{\pm}26.34 &
  \textless\ 0.853\\
After  four  weeks &
  65.95\ensuremath{\pm}34.28 &
  75.06 \ensuremath{\pm}28.90 &
  \textless\ 0.102\\
After  eight  weeks &
  66.69\ensuremath{\pm}30.20 &
  91.55 \ensuremath{\pm}28.76 &
  \textless\ 0.0003\\
After  12  weeks &
  72.45\ensuremath{\pm}28.80 &
  106.99 \ensuremath{\pm}27.61 &
  \textless\ 0.0001\\
After  16  weeks &
  75.30\ensuremath{\pm}27.99 &
  122.26 \ensuremath{\pm}28.95 &
  \textless\ 0.0001\\
After  20  weeks &
  86.80\ensuremath{\pm}28.12 &
  134.65 \ensuremath{\pm}27.20 &
  \textless\ 0.0001\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\bgroup
\fixFloatSize{images/562a4762-1093-4a40-ad5d-c4ee088ac31c-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/562a4762-1093-4a40-ad5d-c4ee088ac31c-upicture1.png}{\includegraphics{images/562a4762-1093-4a40-ad5d-c4ee088ac31c-upicture1.png}}{\includegraphics{562a4762-1093-4a40-ad5d-c4ee088ac31c-upicture1.png}}
\makeatother 
\caption{{Age-based distribution of acne cases}}
\label{f-82008436f635}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/69487513-f1a1-472b-bc9a-eb81e72d6469-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/69487513-f1a1-472b-bc9a-eb81e72d6469-upicture2.png}{\includegraphics{images/69487513-f1a1-472b-bc9a-eb81e72d6469-upicture2.png}}{\includegraphics{69487513-f1a1-472b-bc9a-eb81e72d6469-upicture2.png}}
\makeatother 
\caption{{Sex distribution}}
\label{f-55ccbfe7cc4c}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/a109a6fb-53c6-4117-826a-39abdc47c9bd-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/a109a6fb-53c6-4117-826a-39abdc47c9bd-upicture3.png}{\includegraphics{images/a109a6fb-53c6-4117-826a-39abdc47c9bd-upicture3.png}}{\includegraphics{a109a6fb-53c6-4117-826a-39abdc47c9bd-upicture3.png}}
\makeatother 
\caption{{Site of Acne}}
\label{f-3a80f687b4c2}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/06407b32-840d-4fd1-b9f4-45135c2314e3-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/06407b32-840d-4fd1-b9f4-45135c2314e3-upicture4.png}{\includegraphics{images/06407b32-840d-4fd1-b9f4-45135c2314e3-upicture4.png}}{\includegraphics{06407b32-840d-4fd1-b9f4-45135c2314e3-upicture4.png}}
\makeatother 
\caption{{Previous treatment}}
\label{f-5e60fe905615}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/a33db4cb-0a7d-4d54-a215-dcfcb4c746eb-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/a33db4cb-0a7d-4d54-a215-dcfcb4c746eb-upicture5.png}{\includegraphics{images/a33db4cb-0a7d-4d54-a215-dcfcb4c746eb-upicture5.png}}{\includegraphics{a33db4cb-0a7d-4d54-a215-dcfcb4c746eb-upicture5.png}}
\makeatother 
\caption{{Lipid profile before and after four months of intermittent Adapalene treatment}}
\label{f-f23cfdaf2ff1}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/60769695-feb4-42c2-92a3-09a2c1cb7b03-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/60769695-feb4-42c2-92a3-09a2c1cb7b03-upicture6.png}{\includegraphics{images/60769695-feb4-42c2-92a3-09a2c1cb7b03-upicture6.png}}{\includegraphics{60769695-feb4-42c2-92a3-09a2c1cb7b03-upicture6.png}}
\makeatother 
\caption{{Lipid profile before and after four months of continuous adapalene treatment}}
\label{f-0d7d1115808f}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/77a180e3-255e-40b6-bece-26bbf82169ce-upicture7.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/77a180e3-255e-40b6-bece-26bbf82169ce-upicture7.png}{\includegraphics{images/77a180e3-255e-40b6-bece-26bbf82169ce-upicture7.png}}{\includegraphics{77a180e3-255e-40b6-bece-26bbf82169ce-upicture7.png}}
\makeatother 
\caption{{Comparision of Cholesterol levels in adapalene treatment}}
\label{f-76e19c658724}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/49c4f3cc-f374-4864-95ed-af350c87ddb2-upicture8.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/49c4f3cc-f374-4864-95ed-af350c87ddb2-upicture8.png}{\includegraphics{images/49c4f3cc-f374-4864-95ed-af350c87ddb2-upicture8.png}}{\includegraphics{49c4f3cc-f374-4864-95ed-af350c87ddb2-upicture8.png}}
\makeatother 
\caption{{Comparision of triglyceride levels in adapalene treatment}}
\label{f-8c51d7ae8340}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/15635798-e017-45a8-9829-66d279f0d848-upicture9.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/15635798-e017-45a8-9829-66d279f0d848-upicture9.png}{\includegraphics{images/15635798-e017-45a8-9829-66d279f0d848-upicture9.png}}{\includegraphics{15635798-e017-45a8-9829-66d279f0d848-upicture9.png}}
\makeatother 
\caption{{Comparision of HDL levels of adapalene treatment}}
\label{f-46d465df8ccf}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/c42efcc2-0803-4df6-8693-3d6d566edae6-upicture10.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/c42efcc2-0803-4df6-8693-3d6d566edae6-upicture10.png}{\includegraphics{images/c42efcc2-0803-4df6-8693-3d6d566edae6-upicture10.png}}{\includegraphics{c42efcc2-0803-4df6-8693-3d6d566edae6-upicture10.png}}
\makeatother 
\caption{{Comparision of DL levels of adapalene treatment}}
\label{f-c117ad866145}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/a881514c-d9ef-42b2-8280-5d0b7488ddc2-upicture11.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/a881514c-d9ef-42b2-8280-5d0b7488ddc2-upicture11.png}{\includegraphics{images/a881514c-d9ef-42b2-8280-5d0b7488ddc2-upicture11.png}}{\includegraphics{a881514c-d9ef-42b2-8280-5d0b7488ddc2-upicture11.png}}
\makeatother 
\caption{{Moderate acne}}
\label{f-bcb44d54f503}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/5dc5fee2-de8f-458c-a034-f553bcd954ab-upicture12.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/5dc5fee2-de8f-458c-a034-f553bcd954ab-upicture12.png}{\includegraphics{images/5dc5fee2-de8f-458c-a034-f553bcd954ab-upicture12.png}}{\includegraphics{5dc5fee2-de8f-458c-a034-f553bcd954ab-upicture12.png}}
\makeatother 
\caption{{Severe Acne}}
\label{f-b25870444883}
\end{figure}
\egroup
\textbf{Exclusion criteria }


  
  \begin{enumerate}
  \item \relax Females who refuse to use an appropriate method of birth control during the research, including those who are pregnant, nursing, planning a pregnancy, or who are pregnant.
  \item \relax The existence of any skin condition that can impede the identification or evaluation of acne.
  \item \relax A history of Adapalene, retinoids, or any other component of the test product or RLD hypersensitivity or allergy.
  \item \relax Use of estrogens or other forms of contraception within six months of baseline; such therapy must be continued throughout the research.
  \item \relax The use of oral contraceptives or estrogens for less than three months before baseline must be continued throughout the study.
  \item \relax Use 1) cryodestruction or chemodestruction on the face within one month of baseline or during the trial; 2) Dermal ablation; 3. Photodynamic treatment surgery for acne, 6) Radiation therapy, or 5) intralesional steroids. 
  \item \relax Using spironolactone, systemic steroids, systemic antibiotics, systemic treatment for acne vulgaris (other than retinoids, which require a washout period of six months), or systemic anti-inflammatory drugs within one month of baseline.
  \item \relax Use no later than two weeks before the baseline. 1) Topically applied steroids, 2) Topically applied retinoids, 3) topically applied acne medications, including over-the-counter options, 4) topically applied anti-inflammatory drugs, or 5) topically applied antibiotics.
  \item \relax Allergy to Adapalene.
  \item \relax  The patient is not willing to take Adapalene therapy.
  \end{enumerate}
  The Case description Types for acne research allow researchers to describe lesions that get worse with therapy and are worse than Grade 4. It is advised against enrolling subjects with nodulocystic acne as acne vulgaris participants. In the safety evaluation, those who deteriorate past Grade 4 must be described.

\textbf{Parameters to be studied}

Cholesterol estimation using the dynamic extended stability CHOD- POD endpoint method and ERBA XL as a lipid cleaning agent 300 analyzer manufactured by Transasia  Bio-medicals Ltd.

Estimating triglycerides  by  GPO-PAP endpoint method by ERBA  XL  300 analyzer manufactured  by Transasia Bio-medicals Ltd.

Estimation of  HDL  by immune inhibition method  using analyzer ERBA XL  300 analyzer manufactured  by AGAPPE Diagnostics.

Estimation of LDL  by Friedwald's calculation.

\textbf{Estimation  of Serum Lipid Profile}

\textbf{Serum Total Cholesterol }

The enzymatic End  Point  Method  (Cholesterol   Oxidase  Method)   was  used to quantitatively determine  total cholesterol in human serum using the CHOD-POD endpoint method,  with a lipid clearing agent  by ERBA Manheim analyzer, manufactured  by Transasia Biomedicals Ltd. 

\textbf{Principle}

The cholesterol is identified in the wake of enzymatic hydrolysis and oxidation. The cholesterol esterase hydrolyzes cholesterol esters to create free cholesterol and fatty acids. The enzyme cholesterol oxidase then transforms cholesterol into cholestene-3-one and hydrogen peroxide. In the presence of peroxidase, hydrogen peroxide oxidatively links with 4-aminoantipyrine and phenol to generate red quinoneimine dye, which has a maximum absorbance range of 510{\textendash}530 nm. The amount of total cholesterol in the serum is inversely correlated with the intensity of the red colour.

Cholesterol esterase

Cholesterol ester  +  H20 Cholesterol  + Fatty acids

Cholesterol  oxidase

Cholesterol  +  O2 Cholestene -3-one  +  H2O2 peroxidase

2H2O2  +  phenol  + 4-  Aminoantipyrine  Quinoneimine  +  4H2O  49

\textbf{Reagent  Composition Contents Concentrations }

R1.Reagent

Goods Buffer  100mmol/L,  pH  6.4

4-Aminoantipyrine

0.3mmol/L Phenol 5mmol/L

Peroxidase  \ensuremath{\geq } 3000U/L Cholesterol esterase {\textgreater}200U/L Cholesterol  Oxidase {\textgreater}100  U/L 

\textbf{Preparation  of reagent}

R1 Reagent  {\textendash} contents ready for  use.

\textbf{Procedure}

Cholesterol  was estimated  using the ERBA  XL  300 auto analyzer. The sample used for the assay was 10\ensuremath{\mu }l, and the reagent volume  used  was R1-  1000\ensuremath{\mu }l.

\textbf{Typical  Values in serum plasma}

\textbf{Risk levels}

Value Interpretation \textless\  200 mg/dl Desirable  blood cholesterol 200-  239 mg/dl Border line-high  blood cholesterol \ensuremath{\geq } 240mg/dl High  blood cholesterol  50.

\textbf{Serum triglycerides}

Enzymatic Method (GPO- PAP Method)  was  used to quantitatively determine triglycerides in human serum using the Erbaauto analyzer.

\textbf{Principle}

Following enzymatic hydrolysis utilizing lipoprotein lipase, the triglyceride is identified. Glycerol kinase uses the released glycerol to create glycerol-3-phosphate. Glycerol phosphate oxidase converts glycerol-3-phosphate into dihydroxy acetone phosphate and hydrogen peroxide. The  hydrogen  peroxide in the  presence of  peroxidase oxidizes 4-aminophenazone  and  4- 4-chlorophenol to create the 510{\textendash}530 nm absorbent red quinoneimine dye. The intensity of the red color is proportional to the amount of triglyceride  present in the serum [86]. Triglycerides +  H20 Lipoprotein  lipase Glycerol  + fatty acids combined with ATP Globule kinase ADP plus glycerol-3-phosphate

Glycerol  + ATP Glycerol kinase Glycerol-3-phosphate  + ADP

Glycerol-3-phosphate  +  O2  Glycerol  phosphate oxidase dihydroxy acetone  phosphate +H2O2.

2H2O2  +  4-aminophenazone  + 4- chlorophenol  peroxidase  Quinoneimine +HCl+  4H2O  51

\textbf{Reagent  Composition Contents Concentrations }

Buffer pipes 40mmol/L,  pH  7.0

4-Aminoantipyrine  0.4mmol/L 

Magnesium-ions 2.5mmol/L 

Enzyme Reagent

ATP  2.0mmol/L

Lipoprotein Lipase 4000U/L 

Glycerol-kinase  1500U/L

Glycerol-3-phosphate oxidase  4000  U/L 

Peroxidase  2200U/L

DHBS  0.2mmol/L

\textbf{Preparation  of  Reagent}

Buffer/ Enzyme Reagent {\textendash} Reagents R1 and R2 are prepared for usage. The working reagent is created by carefully combining four parts of R1 and 1 part of R2.

\textbf{Procedure}

Triglyceride  was estimated  using an ERBA auto analyzer. The sample volume  used for the assay was two \ensuremath{\mu }l, and the reagent volume  used  was R1-180 \ensuremath{\mu }\ensuremath{\mu }l

\textbf{Values in serum: Intended cut-off points }

Normal  \textless\  150mg/ dl High  150  {\textendash}  199 mg/dl

Hypertriglyceridemia  200-499 mg/dl  52

Very  high  {\textgreater}  499 mg/ dl

\textbf{Serum  HDL- cholesterol}

The direct method  was  used to determine HDL-cholesterol using quiche HDL quantitatively. Cholesterol with calibrator in an auto analyzer.

\textbf{Principle}

The electrostatic interaction between polyanions and cationic compounds inhibits the response between cholesterol other than HDL and the enzyme for cholesterol testing. The free cholesterol in HDL is converted to hydrogen peroxide by cholesterol oxidase. In the presence of peroxidase, hydrogen peroxide causes the oxidative condensation of EMSE and 4-AA, and the absorbance of the resultant red-purple quinine is measured to determine the HDL cholesterol value [70]. HDL polyanions are not the only lipoproteins that inhibit enzyme reactions.

Cationic substances

HDL (cholesterol esters) +H\ensuremath{_{2}}O cholesterol esterase  HDL (free cholesterol)  + FFA HDL (free cholesterol) +  O\ensuremath{_{2}} +  H cholesterol  oxidase cholestenone +H2O2

2H2O2 +4-AA+EMSE+H3 +  O~peroxidase red-purple  quinine +5H2O 

\textbf{Reagent composition}

HDL {\textendash}C Direct R1 N-ethyl-N-(3-methylphenyl)-Nsuccinylethyenediame(EMSE) HDL-C Direct R2 Cholesterol oxidase 4-Aminoantipyrine HDL {\textendash}C Direct calibrator

\textbf{Preparation of reagents}

The R1 enzyme reagent's usable contents are Ready-to-use and the R2 enzyme reagent.

\textbf{Procedure}

HDL cholesterol  was estimated  using an Erba XL  300 auto analyzer. The sample volume  used for the assay was 5\ensuremath{\mu }L, and the reagent volume  used  was R1  450\ensuremath{\mu }L and R2  150\ensuremath{\mu }L.

\textbf{Normal range }

Male:  35-80mg/dl

Female:  42-88mg/d

\textbf{Serum LDL Cholesterol}

LDL cholesterol in human serum was quantitatively determined using the Friedewald equation. 

Friedewald Equation

[LDL-cholesterol]  = [Total cholesterol]  {\textendash} [HDL- cholesterol]  {\textendash} [Triglyceride/5] Limitations for Friedewald Equation:

There are two main limitations where the Friedewald Equation cannot be applied:


  
  \begin{enumerate}
  \item \relax If the triglyceride concentration is above  400mg/dl. 
  \item \relax VLDL is present in people with type III hyperlipoproteinemia who have this condition. -VLDL is a kind of VLDL that has a higher cholesterol content than VLDL. The calculation of LDL for the current study has considered the restrictions above.
  \end{enumerate}
  \textbf{Risk Levels}

Optimal {\textless}100mg/dl

Near  or above optimal  100 -129 mg/dl

Borderline High  130-159 mg/dl

High  160-  189mg/dl

Very  high {\textgreater}189mg/dl

\textbf{Statistical  analysis using Graph Pad Prism  version  8.03}

Using Graph Pad Prism version 8.03, statistical data analysis was performed.
    
\section{Results and Discussion}
100 patients  diagnosed  to have moderate  to severe acne vulgaris attending the Dermatology  \&  Venereal Diseases  OPD at Government Medical College,  Nellore,  who fulfilled the inclusion and exclusion criteria,  were studied from October  2019- February  2020. The study aimed to assess the lipid profile changes in intermittent and continuous Adapalene  topical therapy in moderate  to severe acne vulgaris cases.

The majority of the  patients, i.e.,  84  patients, were in the age  group of  15-24 years,  20  patients were in the age group of  25-34years, and  four  patients were in the age  group of  35-45 yrs.

Of the 100 patients, 60 (58\%) were males and 45 (42\%) were females. There  was an overall male  preponderance, with a male-to-female ratio of  1.38:1.

Eighty-five patients had facial acne, which was the most prevalent type. Six patients had Truncal, and 15 had face and Truncal acne. (Tables~\ref{tw-3dc2f392c1e8}, \ref{tw-be514cf5313b} and~\ref{tw-6ff1d4dae56b}, Figures~\ref{f-3a80f687b4c2}, \ref{f-82008436f635} and~\ref{f-55ccbfe7cc4c})

Regarding the  previous treatment taken  by the  patients, the majority of the  patients, i.e.,  42 patients, had taken treatment with both antibiotics and topical therapy,  34  patients had taken treatment  with antibiotics alone, and  15  patients had taken topical treatment.  With  topical therapy alone,  six  patients  had taken treatment with isotretinoin;  two  patients had Adapalene, and  20  patients had not taken any treatment before.

On cutaneous assessment, it  was found that at  week  0,  60  \%  of patients had grade II acne, and 40\% had  grade III acne. At  week 4,  10\% had  grade I,  64\% had  grade II acne, and  26\% had grade III acne. At  12  weeks, 5\% of patients had grade 0 acne, 82\% had grade I~acne, and 13\% had  grade II acne. After completing treatment, at  16 weeks, it  was found that  5\% had  grade 0,  93\% had  grade I, and 2\% had  grade II. (Tables~\ref{tw-f6319e7f610a} and~\ref{tw-09dc6613b055})  

Serum cholesterol, triglycerides, and  HDL significantly changed on continuous Adapalene therapy.  Values were elevated  when compared with baseline but  were above average levels. (Table~\ref{tw-5fe258fe371d}, Figures~\ref{f-0d7d1115808f}, \ref{f-5e60fe905615} and~\ref{f-f23cfdaf2ff1}) 

\textbf{Cholesterol}

The measured baseline cholesterol in the intermittent therapy group was 126.3535.09, and the values at four weeks, eight weeks, 12 weeks, and 16 weeks later, as well as after the treatment, were 128.75\ensuremath{\pm}35.46,  132.79\ensuremath{\pm}32.95,  138.87\ensuremath{\pm}34.46,  145.62\ensuremath{\pm}30.72 and  156.58\ensuremath{\pm}25.70 respectively. Compared to baseline, there was a rise in cholesterol at every interval, but it stayed within normal limits. A fundamental value that was measured of cholesterol in the continuous therapy  group  was 115.55\ensuremath{\pm}25.09, then after at  4,  8,  12wk,  16, and the end  of the  treatment  were 136.85\ensuremath{\pm}28.53,  157.85\ensuremath{\pm}26.22,  178.15\ensuremath{\pm}27.78,  195.25\ensuremath{\pm}28.78 and  210.56\ensuremath{\pm}16.57 respectively. There  was a significant increase in cholesterol compared to baseline and above the upper limit at all intervals. (Table~\ref{tw-d28172bf75b4}, Figure~\ref{f-76e19c658724}). Cholesterol levels compared between intermittent and continuous therapy at  four weeks of treatment were  128.75\ensuremath{\pm}35.46 and 136.85\ensuremath{\pm}28.53. The difference  was statistically insignificant, with a value of  0.142. When reached at  8, the values  were  132.79\ensuremath{\pm}32.95 and  157.85\ensuremath{\pm}26.22, and the difference was statistically significant  with a p-value (0.0001). At  12, the values  were  138.87\ensuremath{\pm}34.46 and  178.15\ensuremath{\pm}27.78, and the difference  was statistically significant with a p-value(0.0001). At  16, the values  were  145.62\ensuremath{\pm}30.72 and  195.25\ensuremath{\pm}28.78, and the difference  was statistically significant with a p-value(0.0001). At  20wk, the values  were  156.58\ensuremath{\pm}25.70 and  210.56\ensuremath{\pm}16.57, and with a p-value of (0.0001), the difference was statistically significant. (Table~\ref{tw-d28172bf75b4})

\textbf{Triglyceride}

Triglycerides' baseline values in the group receiving intermittent treatment were 98.59\ensuremath{\pm}45.02, then after at  4,  8wk,  12wk,  16wk, and at the end of the treatment  were  98.49\ensuremath{\pm}45.95,  105.48\ensuremath{\pm}45.08,  108.50\ensuremath{\pm}43.79,  115.26\ensuremath{\pm}45.99 and  126.90\ensuremath{\pm}42.25 accordingly. Compared to the baseline, triglycerides increased at every interval but within normal limits.

The measured baseline values of Triglycerides in the continuous therapy  group  were 98.57\ensuremath{\pm}24.01 then after 4 4,  8wk,  12wk,  16wk, and at the end of the  treatment  were  115.50\ensuremath{\pm}24.65,  132.09\ensuremath{\pm}22.91,  150.52\ensuremath{\pm}20.20,  165.25\ensuremath{\pm}18.82 and  188.90\ensuremath{\pm}16.25 respectively. There  was a significant increase in triglycerides at all the intervals compared with baseline and above the standard limit. (Table~\ref{tw-45ccb02f6584}, Figure~\ref{f-8c51d7ae8340})

Triglyceride levels compared between intermittent and continuous therapy at  four weeks of treatment were 98.49\ensuremath{\pm}45.95 and  115.50\ensuremath{\pm}24.65. The  difference  has been statistically insignificant,  with  a value of  0.0440. When compared at  8, the values  were  105.48\ensuremath{\pm}45.08 and  132.09\ensuremath{\pm}22.91, and the difference was statistically significant  with a p-value (0.0002). At  12, the values  were  108.50\ensuremath{\pm}43.79 and  150.52\ensuremath{\pm}20.20, and the difference  was statistically significant with a p-value (0.0001). At  16, the values  were  115.26\ensuremath{\pm}45.99 and  165.25\ensuremath{\pm}18.82, and the difference  was statistically significant with a p-value(0.0001). At  20wk, the values  were  126.90\ensuremath{\pm}42.25 and  188.90\ensuremath{\pm}16.25, and the  difference  was statistically significant with a p-value(0.0001).

\textbf{HDL}

HDL levels in the intermittent therapy group were measured at baseline at 50.26 11.38 and again at 4 wk, 8,  12,  16, and at the end of the treatment  were 50.48\ensuremath{\pm}12.69,  49.63\ensuremath{\pm}13.95,  51.08\ensuremath{\pm}12.60,  49.62\ensuremath{\pm}12.99 and  48.45\ensuremath{\pm}10.09 accordingly. Compared to baseline, HDL decreased at every interval but stayed within normal limits. The measured baseline values of  HDL in the continuous  therapy  group  were,  44.64\ensuremath{\pm}10.32 then after at 4,  8wk,  12wk,  16wk, and at the end of the treatment  were 43.86\ensuremath{\pm}9.20,  45.00\ensuremath{\pm}11.28,  41.80\ensuremath{\pm}9.59, 41.42\ensuremath{\pm}8.56,  40.98\ensuremath{\pm}7.91 respectively. There  was  a significant reduction in HDL relative to baseline at each period. (Tables~\ref{tw-61a70dfbb2b4}, \ref{tw-78d7bef651e2} and~\ref{tw-be514cf5313b}, Figures~\ref{f-46d465df8ccf}, \ref{f-bcb44d54f503} and~\ref{f-b25870444883}).

HDL levels compared between intermittent and continuous therapy at  four weeks of treatment  were 50.26\ensuremath{\pm}11.38 and  44.64\ensuremath{\pm}10.32. The difference  has been statistically insignificant with a p-value (0.0174). When compared at  8, the values  were  49.63\ensuremath{\pm}13.95 and  45.00\ensuremath{\pm}11.28, and the difference  was statistically slight with p-value(0.0660). At  12, the values  were  51.08\ensuremath{\pm}12.60 and  41.80\ensuremath{\pm}9.59, and the  difference  was statistically insignificant  with a p-value(0.0052). At  16, the values  were  49.62\ensuremath{\pm}12.99 and  41.42\ensuremath{\pm}8.56, and the difference  was statistically significant with a p-value(0.0028). At  20wk, the values  were  48.45\ensuremath{\pm}10.09 and  40.98\ensuremath{\pm}7.91, and the  difference  was statistically significant with a p-value(0.0084).

\textbf{LDL}

LDL baseline values in the group receiving intermittent treatment were 59.62 \ensuremath{\pm}32.45, then after at 4,  8, 12wk,  16wk, and the end of the treatment  were 65.95\ensuremath{\pm}34.28,  66.69\ensuremath{\pm}30.20,  72.45\ensuremath{\pm}28.80,  75.30\ensuremath{\pm}27.99,  86.80\ensuremath{\pm}28.12 respectively. Compared to baseline, there was an increase in LDL at every interval, but it was within normal limits. HDL baseline value measured in the continuous therapy  group  was 59.62 \ensuremath{\pm}32.45, then after at 4wks,  8wk  ,  12wk,  16wk and  following the course of treatment were 65.95\ensuremath{\pm}34.28,  66.69\ensuremath{\pm}30.20, 72.45\ensuremath{\pm}28.80,  75.30\ensuremath{\pm}27.99,  86.80\ensuremath{\pm}28.12 respectively. There  was significant every interval saw a rise in LDL compared to baseline. (Tables~\ref{tw-b4f447d5c781} and~\ref{tw-09dbbf277eaf}, Figures~\ref{f-46d465df8ccf} and~\ref{f-c117ad866145}).

LDL levels compared between intermittent and continuous therapy at  four weeks of treatment  were 65.95\ensuremath{\pm}34.28 and  75.06 \ensuremath{\pm}28.90. The difference  has been statistically insignificant  with a p-value (0.101). When compared at  8, the values  were  66.69\ensuremath{\pm}30.20 and  91.55 \ensuremath{\pm}28.76, and the  difference  was statistically significant with a p-value (0.0001). At  12, the values  were  72.45\ensuremath{\pm}28.80 and  106.99 \ensuremath{\pm}27.61, and the difference  was statistically significant with a p-value(0.0001). At  16, the values  were  75.30\ensuremath{\pm}27.99 and  122.26 \ensuremath{\pm}28.95, and the contrast  was statistically significant with a p-value(0.0001). At  20wk, the values  were  86.80\ensuremath{\pm}28.12 and  134.65 \ensuremath{\pm}27.20, and the difference  has been statistically significant with a p-value(0.0001).
    
\section{DISCUSSION}
Acne vulgaris is  a multifactorial disease characterized clinically  by inflammatory and non-inflammatory lesions. Successful acne therapy dramatically improves acne and minimizes its effects. Adapalene is a  drug  that acts on all pathogenic factors and is associated with side effects.  The study aimed to assess the lipid profile changes in intermittent and continuous Adapalene  topical therapy in acne vulgaris.

A study  done  by Stern et  al. showed the  prevalence of acne  was  virtually  100\%  by  mid-teens in both the sex. Another survey  by Smithard et al. showed that the majority of acne was 56\% in boys and  45\%. Girls between  14-16 yrs, with moderate  to severe acne in  11\%.10.

Similar to the study  done  by Smithard et  al., in  our research, out \% of  100  patients,  56\%  were males, and  44\%  were female. There  was an overall  preponderance of males. In  a study by  Goulden et  al.,  25\% of acne patients had  a mean age of  24 years, and  8\% had late onset (over  25 years)acne. In our study, the mean age  was found to be  21.8 years. Our study showed intermittent regimen with less effects on lipid  profile.  Our study reported that On periodic Adapalene medication, blood triglycerides, HDL, and LDL exhibited no discernible changes. Compared to the baseline, values were higher at all intervals but were within the average level.  Our result  was similar  to an RCT conducted  by Akman et al.,  which compared intermittent. Adapalene treatment with conventional treatment reported that an intermittent regimen represented an effective alternative treatment with fewer side effects. There are studies  done independently  to evaluate the lipid profile changes in traditional medicine, showing a significant increase in cholesterol, triglycerides, and LDL.

An RCT of 90  patients with severe acne showed that  patients  using Adapalene  daily for three months developed a significant increase in cholesterol and  triglyceride levels.  Another study indicates stopping the therapy when triglyceride levels are above   800mg/dl because of the risk of pancreatitis. 

Our study found that Continuous Adapalene medication resulted in significant changes in serum cholesterol, triglycerides, and HDL. Values were higher than baseline, but they were above average level.  As reflected in our  present study, it showed statistically significant changes compared with the baseline at all intervals. The effect of Adapalene is  dose-dependent because usage of the  drug  daily could have been probable reason for influencing the increase in the lipids in continuous therapy compared with intermittent treatment.

Our study proved that  a lipid  profile change in intermittent therapy was less than in continuous treatment. Intermittent therapy is better than constant therapy. Further,  we can standardize the treatment by extending the study to a large group of patients.

Some studies have shown the effects of  lipid  profiles in continuous therapy. Another multicenter randomized controlled trial showed that low-dose Adapalene had significantly elevated serum triglycerides.

Previous studies have examined serum lipid abnormalities associated  with conventional Adapalene  use and have estimated the incidence of  lipid abnormalities.

The  present study  demonstrated that intermittent Adapalene therapy  has  little effect on plasma cholesterol,  triglyceride, LDL, and  HDL, and  the results or changes  were  within the standard acceptable level. Lipid changes  were more frequent in continuous therapy  when compared with intermittent regimens.  Other side effects were less in an intermittent regimen. Because the side effects of Adapalene are  dose-dependent, it could be one reason why the lipid  profile  was significant in continuous therapy. The changes are reversible on stopping the treatment. Patients  with acne  who develop a considerable increase in triglyceride levels  during  Adapalene therapy are at increased risk for future  hyperlipidemia and metabolic syndrome. In his study, Kannelet et al. commented on the potential cardiovascular risk of this lipid change.
    
\section{Conclusion}
The  present  study demonstrated  that  intermittent  Adapalene therapy has  little effect  on  plasma cholesterol,  triglyceride, LDL, and  HDL, and  the results  or changes  were  within  the  standard acceptable  level. At the same time, continuous  Adapalene therapy caused an  increase  in cholesterol,  triglycerides, LDL, and  HDL above  the  normal  range  with a grade  1  increase. Lipid changes  were more frequent  in continuous therapy when compared  with  intermittent  regimens.  Other  side effects  were  less  in the  intermittent regimen. Our  study  found  that  intermittent  Adapalene regimens are clinically effective, cost-effective, less impacting plasma lipid levels, and considered a better alternative.
    
\section{Acknowledgment}
The authors are thankful to the Principal (Dr. Y. Prapurna Chandra) \& HOD (Dr. Yerikala Ramesh) from Ratnam Institute of Pharmacy, Pidathapolur, SPSR Nellore, for providing the necessary facilities to carry out this research work.

\textbf{Conflict of Interest}

The authors declare no conflict of interest, financial or otherwise.

\textbf{Funding Support}

The authors declare that they have no funding for this study.
    

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