Clinical and Life Quality Improvement, and IL-17 Serum Level in

Psoriasis Patients Treated with Metothrexate Injection: A Pilot Study

in 15 Severe Psoriasis Cases

Prasta Bayu Putra

, Kusnindita Noria Rahmawati

, Adissa Tiara Yulinvia

, Sunardi Radiono

, Dyah

Ayu Mira Oktarina

Department of Dermatology and Venereology, Gadjah Mada University/Sardjito General Hospital, Yogyakarta-Indonesia

Department of Dermatology and Venereology, Erythrosquamous Disease and Phototherapy Subdivision, Gadjah Mada

University/Sardjito General Hospital, Yogyakarta-Indonesia

Department of Dermatology and Venereology, Dermatopathology Subdivision, Gadjah Mada University/Sardjito General

Hospital, Yogyakarta-Indonesia

Keywords: Severe Psoriasis, Methotrexate Injection, Clinical Improvement, Life Quality Improvement, IL-17 serum

level

Abstract: Psoriasis is an autoimmune T cell mediated chronic skin disorder which is difficult to treat. Conventional

therapy using oral methotrexate in severe cases often showed unsatisfying result. Our department was

developing methotrexate injection protocol for severe cases to improve patient treatment and life quality and

for achieving quick remission. Objective: This pilot study was aimed to observe efficacy of methotrexate

injection 50mg/week for 6 consecutive weeks. Method: Study subjects were severe psoriasis patients that

unresponsive to any conventional therapies. PASI score and DLQI score improvement and serum IL-17 level

at the end of study were measured. Result: PASI-100 was achieved by 12 subjects (80%) at the end of sixth

weeks. DLQI score were significantly different (p<0.001) after sixth injection and subjects serum IL-17 level

were not significantly different with healthy peoples at the end of study. Conclusion: Methotrexate injection

50mg/week for 6 consecutive weeks initiation can be considered as an effective treatment for severe psoriasis.

Further studies with larger samples and longer observation period are needed to determine long term efficacy,

side effects, and protocol guideline policy.

1 INTRODUCTION

Psoriasis is an autoimmune T cell mediated chronic

skin disorder with polygenic predisposition and

clinical manifestation such as papule and

erythematous plaque with thick scale, pustular, or

erythroderma (Gudjonsson et al., 2012). Psoriasis

pathogenesis is run by IL-23/Th17 axis, in which IL-

23 is Th17 cell activator, and IL-17 is the prime

secreted cytokine. Recent study also reported that IL-

23 and IL-17 can be used to assess psoriasis remission

(Chiricozzi, 2014; Karczewski et al., 2016).

Psoriasis often need long term therapy and

difficult to treat. Conventional therapeutic modalities

that can be used for psoriasis treatment consist of

topical agent, systemic, and phototherapy. Topical

corticosteroid, vitamin D analogues, tazaroten, and

calcineurin inhibitor can be used as topical therapy.

Cyclosporine, methotrexate, acitretin, fumaric acid

esther, hydroxyurea, mychophenolate mofetil, and

sulfasalazine can be used as systemic therapy.

Phototherapy modality consist of Narrowband

Ultraviolet B (NB-UVB), Broadband Ultraviolet B

(BB-UVB), and Psoralen with Ultraviolet A (PUVA)

(Gudjonsson et al., 2012).

Methotrexate is the prime choice for systemic

conventional therapy in psoriasis treatment that has

anti-proliferative effect by inhibition of DNA

synthesis giving anti-inflammatory and

immunosuppression effect (Puig, 2014; Yélamos &

Puig, 2015)

Mild to severe psoriasis and psoriasis that

unresponsive to topical therapy and phototherapy are

the indications of methotrexate administration.

Methotrexate as single psoriasis drug need 1-8 weeks

to achieve therapeutic effects. High dose

methotrexate (15-25 mg/week) is more effective than

176

Putra, P., Rahmawati, K., Yulinvia, A., Radiono, S. and Oktarina, D.

Clinical and Life Quality Improvement, and IL-17 Serum Level in Psoriasis Patients Treated with Metothrexate Injection: A Pilot Study in 15 Severe Psoriasis Cases.

DOI: 10.5220/0008153401760180

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 176-180

ISBN: 978-989-758-494-7

low dose (7,5-15 mg/week) (Dogra & Mahajan,

2013).

The usual adverse effects of methotrexate such

as nausea, vomitus, bone marrow depression, folic

acid deficiency, and hepatotoxicity have been

reported. Cumulative dose more than 3 gram

increasing the hepatotoxicity risk (Pathirana et al.,

2009).

In severe psoriasis cases, the conventional therapy

using oral metothrexate often showed unsatisfying

results with low clinical and life quality improvement

(Gudjonsson et al., 2012). Due to the the disease

severity and socio-economic limitation, our

department tried to develop methotrexate injection

protocol. The protocol is using methrotrexate

injection 50mg/week for 6 consecutive weeks in

phase I, followed by two 50mg methotrexate injection

per two weeks in phase II and two 50mg methotrexate

injection per month for phase III. This is the pilot

study that observe efficacy of methotrexate injection

50mg/week for 6 consecutive weeks (phase I) in the

treatment of severe psoriasis from the clinical and life

quality improvement and serum IL-17. The result of

this study can be used as baseline data for further

study for determining efficacy, side effects, and

protocol guideline policy in severe psoriasis cases.

2 METHODS

The study was conducted in Dermatology and

Venereology Clinic and Ward Dr. Sardjito General

Hospital, and Dermatology and Venereology

Department Faculty of Medicine Gadjah Mada

University. All procedures were performed after

ethical clearance gained from Medical and Health

Research Ethics Committee of Faculty of Medicine,

Gadjah Mada University. Our study subjects

population were severe psoriasis patients that treated

regularly in Dr. Sardjito Hospital Yogyakarta during

September to December 2017 period and previously

unresponsive to any conventional psoriais therapies.

Selected subjects in this study were erythroderma

psoriatica or psoriasis vulgaris patients with PASI

score more than 25, who previously unresponsive to

conventional therapies. Patients with other

autoimmune disease, immunodeficiency, pregnancy

and lactation, obesity with BMI>30kg/m

, severe

anemia, in combination therapy with other

immunosuppressive drugs, renal failure, elevated

lived transaminase enzyme, hepatitis, or cirrhosis

were excluded from this study. Patients were

informed about the protocol, asked for consent and

recruited as study subjects if they signed the informed

consent form. Methotrexate 50 mg/week for 6

consecutive weeks was administered via

intramuscular injection.

Psoriasis disease severity and remission were

assessed using Psoriasis Area and Severity Index

(PASI) score at the beginning of the therapy

(baseline) and one week after each of methotrexate

injection until 6

injection. Patient’s life quality was

assessed using Dermatological Life Quality Index

(DLQI) score at the beginning of the therapy

(baseline) and one week after 6

methotrexate

injection. Blood samples from the subjects were taken

at one week after the 6

injection and from healthy

peoples without autoimmune disease or systemic

infection, to measure IL-17A serum level using

Komabiotech

human IL-17A ELISA kit. The data

were analyzed using IBM SPSS

version 24

comparative and correlation test, with the p value

<0.05 was considered as significant result.

3 RESULT

During September to December 2017 there were 15

severe psoriasis patients that undergo methotrexate

injection therapy in Dermatology and Venereology

Clinic and Ward unit Dr. Sardjito General Hospital

Yogyakarta. Mean subject’s age was 46 ± 3,98 years

old, which is range from 18 to 66 years old and consist

of 12 men and 3 women. From the occupation, most

of the subjects were farmer and labor (Table 1). The

baseline PASI score and DLQI score were

significantly decreased after 6

injection, and there

was no significant serum IL-17 level difference found

between subjects and healthy peoples at the end of

therapy (Table 2).

In this study 87% subjects achieved PASI-75 at

the end of therapy, which was achieved mostly after

the third injection. The PASI-100 was achieved

mostly after the fourth injection and at the end of

therapy was achieved by 80% subjects. There were

13% and 20% non responsive subjects that improved

clinically, but didn’t achieved PASI-75 and PASI-

100 respectively at the end of study (Chart 1). From

statistic analysis test result, there was significant

linear correlation between PASI score improvement

(ΔPASI score) and DLQI score improvement

(ΔDLQI score) with strong correlation power (r=

0.641, p= 0.01) (Chart 2).

Clinical and Life Quality Improvement, and IL-17 Serum Level in Psoriasis Patients Treated with Metothrexate Injection: A Pilot Study in

15 Severe Psoriasis Cases

177

Table 1. Subject characteristics

Characteristics Total (%) Mean

Sex Male 12 (80%)

Female 3 (20%)

Age <40

ears ol

4 (27%) 46 ± 3,98

40-60

ears ol

8 (53%)

>60

ears ol

3 (20%)

Job Farme

5 (33%)

Labo

4 (27%)

Studen

2 (13%)

Housewife 2 (13%)

Office wor

1 (6,7%)

Teache

1 (6,7%)

Diagnosis Er

throderma Psoriatica 9 (60%)

Psoriasis Vul

aris 6 (40%)

Table 2. PASI scores, DLQI scores, & serum IL-17 levels data

Measurement Period Mean p Value

PASI Score Baseline 51,56 ± 4,41 0.001

Post 1

ection 32,1 ±3,04

Post 2

ection 18,52 ± 2,38

Post 3

ection 9,6 ± 1,8

Post 4

ection 3,92 ± 1,56

Post 5

ection 2,14 ± 1,27

Post 6

ection 1,36 ± 1,08

DLQI Score Baseline 27.6 ± 0,66 0.001

Post 6

ection 5,27 ± 0,78

Serum IL-17 Level Health

Peoples 7,75 ± 0,41 0.070

Sub

ects (Post 6

ection) 9,68 ± 0,79

p value is obtained from Wilcoxon comparative test

p value is obtained from Mann Whitney comparative test

Chart 1. Subject PASI-75, PASI-100

(ΔPASI score) and DLQI score improvement (ΔDLQI score) with strong correlation power (r= 0.641, p= 0.01)

(Chart 2).

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178

Chart 2. ΔPASI score & ΔDLQI score correlation

p value is obtained from Spearman correlation test

correlation coefficient (r) is obtained from Spearman correlation test

*ΔPASI & ΔDLQI Score obtained from difference between baseline and post 6

injection score

4 DISCUSSION

Methotrexate is the prime choice for systemic

conventional therapy in patient with extensive,

refractory, or severe psoriasis. Methotrexate

monotherapy in psoriasis treatment show various

responses depend on the administered dose (Dogra &

Mahajan, 2013). When low dose is used (7,5-

15mg/week), PASI-75 response is achieved by 24%

patients at 12

week. When higher dose is used (15-

25mg/week), PASI-75 response is achieved by 42-

60% patients at 16

week (Cabello et al., 2017). In

this study the earliest PASI-75 and PASI-100

responses was achieved at 2

week by 26% subjects

and at 3

week by 13% subjects respectively by using

50mg/week methotrexate dose. These findings are in

line with previous studies that higher dose of

methotrexate could induce quicker remission in study

subjects.

IL-17 is a cytokine that has role in psoriasis

pathogenesis and host defence against pathogens such

as bacteria and fungal. IL-17 cytokine has 6 subunits

that consist of IL-17 (A-F) and 5 receptor subunits

that consist of IL-17R (A-E). IL-17A cytokine

subunit and IL-17RA and IL-17RC receptor subunits

are the subunits that have major role in psoriasis

pathogenesis (AbuHilal et al., 2016)

The importance of IL-17 in the pathogenesis can

be used to assess psoriasis remission (Karczewski et

al., 2016). In this study we found that the subject’s

serum IL-17 level after 6

injection had no significant

difference with the healthy peoples and we assumed

the remission was achieved. However, IL-17 serum

level in study subjects was still higher than in healthy

peoples.

Dermatological life quality index score is the most

often used tool for assessing patient life quality due

to its reliability and applicability. Revicki et al (2008)

study on moderate to severe plaque psoriasis reported

that PASI score improvement had correlation with

DLQI score improvement (Revicki et al., 2008). The

same results had been found in this study, in which

the PASI score and DLQI score improvement

significantly correlated. Significant difference also

can be found between baseline and after 6

injection

in DLQI score and PASI score as well.

In this study we also found that the earliest PASI-

75 and PASI-100 responses were achieved by all <40

years and >60 years old subjects and some of 40-60

years old subjects. All of non responsive subjects

derived from 40-60 years old subjects showed PASI

score improvement, however they did not achieved

PASI-75 and PASI-100 responses after 6 consecutive

weeks of 50mg/week methotrexate injection. Daily

Clinical and Life Quality Improvement, and IL-17 Serum Level in Psoriasis Patients Treated with Metothrexate Injection: A Pilot Study in

15 Severe Psoriasis Cases

179

activity, job, and environmental exposure might have

role in this condition, as the subject’s job majority are

farmers and labors that usually work without

protective equipment, which can triggering new

lesions formation or aggravating the old lesions

(Mahler et al., 2014).

5 CONCLUSION

This study reported that methotrexate injection

protocol 50mg/week for 6 consecutive weeks

initiation can be considered as an effective treatment

for severe psoriasis. Most of the subjects had

achieved full remission and significantly improved

quality of life at the end of protocol. Both clinical and

life quality improvement were significantly

correlated each other in this study. Further studies

with larger samples and longer observation period are

needed to determine long term efficacy, side effects,

and protocol guideline policy.

ACKNOWLEDGEMENT

This study was self funded by the authors without

using any research grant, scholarship, or sponsorship.

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