Open Journal of Stomatology, 2011, 1, 13-17 OJST
doi:10.4236/ojst 12003 Published Online June 2011 (
Published Online June 2011 in SciRes.
Efficacy of IMOD in the treatment of oral lichen planus
Efficacy of IMOD in oral lichen planus
Farzaneh Agha-Hosseini1, Iraj Mirzaii-Dizgah2, Mohammad Abdollahi3, Neda Akbari-Gillani1
1Department of Oral Medicine/Dental Research Center, Dentistry School, Tehran University of Medical Sciences, Tehran, Iran;
2Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran;
3Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
E-mail:;; mohammad@t .ir
Received 17 March 2011; revised 26 April 2011, accepted 13 May 2011.
Objectives: Oral lichen planus (OLP) is a chronic,
immunologically mediated, mucocutaneous disorder.
A wide range of topical and systemic therapies have
been used in the treatment of OLP. The efficacy of
IMOD (an Iranian new immunomodulator drug, con-
taining selenium, carotene, and flavonoids) in the
management of oral lichen planus was evaluated.
Study design: In a before-after clinical trial study,
thirty patients (21 women and 9 men; age range 35 -
66 years with 112 lesions) with lichen planus were
enrolled. The study covered a three-month period of
therapy by IMOD (400 mg/day) and a three-month
follow-up period after drug cessation. Outcome mea-
sures include soreness relief based on the “nu-meric
scale”, and clinical improvement of lesion size and
score. Saliva levels of TNF-α was analysed at the
baseline and after treatment by ELISA. Statistical
analysis of Wilcoxon and paired student’s t-test were
used. Results: Approximately 85% of patients showed
partial to complete improvement and re-mained sym-
ptom free after drug cessation. There was no signifi-
cant difference in mean saliva TNF-α level before and
after the treatment. Conclusion: These results suggest
that IMOD seems to be an effective alternative treat-
ment for OLP and TNF-α may not be a good indica-
tor for monitoring therapeutic response of OLP.
Keywords: Oral Lichen Planus; IMOD; TNF-α
Oral lichen planus (OLP) is a chronic, immunologically
mediated, mucocutaneous disorder [1]. Prevalence rate
reported for OLP varies between 0.5% and 2.2% in the
literature, and the mean age at the time of diagnosis is
approximately 55 years. Despite the self-limiting nature
of cutaneous lesions, oral lesions are chronic and rarely
undergo spontaneous remission, and are potentially pre-
malignant. World Health Organization has categorized
OLP as a pre-cancerous condition, which is “a general
state associated with a significant increased risk of can-
cer”. The pathogenesis of OLP is unclear. It was shown
that OLP patients have more cellular lipid peroxidation
[2]. Both antigen specific and non-specific mechanisms
maybe involved. Antigen specific pathways include a
cell mediated immunological response to an induced
antigenic change in the oral mucosa [1], in which cyto-
toxic CD8+ T cells trigger the apoptosis of epithelial
cells following formation of autoreactive T lymphocytes
A wide range of topical and systemic therapies have
been used in the treatment of OLP. Since the etiology
behind OLP is unknown, basic conditions are lacking for
development of preventive therapies. Several topical
drugs have been suggested, including steroids, calcineurin
inhibitors (cyclosporine and tacrolimus), retinoid and
ultraviolet phototherapy [3]. Among these, topical ster-
oids are widely used and have been accepted as the first
choice treatment [3], because they have anti- inflamma-
tory and anti-immunologic effects at the same time. But
their prolonged use should be avoided, because of the
associated adverse effect such as candidiasis over infec-
tion, hypothalamic-pituitary-adrenal axis suppression, skin
fragility and telangectasis, and lesion recurrence after
treatment cessation [4].
IMOD is an Iranian new immunomodulator drug (in-
ternational publication number: WO 2007/087825A1)
with herbal origin. It is produced from a combination of
ethanolic Rosa sp Urtica Dicica and Tanacetum Vulgare
extracts, contains selenium, carotene, flavonoids and urea,
and having been exposed to a pulsed electromagnetic
field. The immunomodulatory mechanisms of IMOD are
not clearly understood, but it can increase CD4 + lym-
phocyte count after a course of treatment of 1 to 3 months.
Its effect is also preserved for a long period after cessa-
F. Agha-Hosseini et al. / Open Journal of Stomatology 1 (2011) 13-17
Copyright © 2011 SciRes. OJST
tion of treatment. It has passed 3 phases of clinical trial
and there were no adverse effects found. Pregnancy and
breast feeding is the only contra-indications of this drug.
Considering the durability, safety and immunologic ef-
fects, it could be used in treatment of immunologic dis-
orders [5].
Serum or saliva level of TNF-α has been used in some
studies for monitoring the therapeutic response of OLP
[6,7]. TNF-α is a multi-functional cytokine that mediates
inflammation, immune response, and apoptosis, and also
has a significant role in normal development and homeo-
stasis of several organs [8]. Positive statistical correla-
tion exists between TNF-α level in serum and saliva. On
the other hand, saliva collection is non-aggressive and
more cost effective.
The purpose of this study was to evaluate the efficacy
of IMOD in the relief of symptoms and signs of OLP
lesion. We have also measured the level of TNF-α in
unstimulated whole saliva before and after treatment.
This was an open label before-after clinical trial study
enrolling 30 patients (21 females and nine males). The
study cases were selected from patients referred to the
Oral Medicine Department, Faculty of Dentistry, Tehran
University of Medical Sciences.
Inclusion criteria were the presence of symmetric re-
ticular or papular lesions with or without erosive/atro-
phic components proven by biopsy. Histopathological di-
agnosis of OLP (Presence of well-defined band like
zones of inflammatory infiltration confined to the super-
ficial part of the connective tissue, consisting mainly of
mature lymphocytes—vacuolar alteration of the basal
layer of the epithelium), was based on “a modified defi-
nition of the World Health Organization” [9]. The pa-
tients were required to sign an informed consent ap-
proved by the ethics committee of Tehran University of
Medical Sciences, and to be available for monthly ap-
pointments up to 6 months. Exclusion criteria were his-
tological sign of dysplasia, lichenoid drug reactions, and
drug consumption in the past month, pregnancy, breast
feeding or any kind of localized or systemic disease.
Patients receiving immunosuppressive or immunomodu-
latory treatments or any kind of systemic or local drugs
were either eliminated or asked to discontinue their treat-
ment for a minimum of 1 month before entering the in-
vestigation. Patient who had lesions adjacent to amalgam
filling were also excluded from the study sample.
Data associated with demographic, medical history,
symptoms and clinical score of the lesion at the baseline
were documented by an oral medicine specialist. Each
patient received IMOD in the form of a daily single dose
capsule (400 mg) for 90 days. All participants were ex-
amined at baseline, after 2 weeks and at months 1, 2, 3, 4,
5 and 6 in order to evaluate treatment efficacy. The clin-
ical data or lesion score (LS) as an index of overall clin-
ical improvement was scored as: 0 no lesion, 1 hyperk-
eratotic lesion, 2 atrophic areas < 1 cm, 3 atrophic areas
> 1 cm, 4 erosive areas < 1 cm, and 5 erosive areas >1
cm. A zero value equates to being pain free, 1 indicates
low degree of pain, 2 moderate pain, 3 severe pain, and 4
very severe pain [10].
A scaled tongue blade was used to assess the size of
lesions [11]. Patients were given an oral examination,
their lesions photographed, and then assessed against the
numeric scale. Symptomatic response (SR) for each pa-
tient was calculated by subtracting the initial numeric
scale from final score. Similarly, clinical response was
estimated through subtraction LS values obtained in the
first and last examination sessions. Positive and negative
values were considered as improvement and deteriora-
tion, respectively.
The saliva level of TNF-α was measured at baseline,
and at the end of treatment period. The unstimulated
whole saliva (UWS) was collected between 9:00 a.m.
and 12:00 a.m. The patients abstained from eating,
drinking and smoking for at least 2 hours prior to the
sampling. All subjects were requested to swallow first,
tilt the head forward and then expectorate WUS into a
sterile centrifugal tube without swallowing, for 5 - 15
minutes. The samples were then frozen until the time of
analysis. TNF-α tests were performed by using ELISA
kits (BioSource, Nevellis, Belgium).
Analysis and comparison of symptomatic and clinical
responses before and after treatment were performed
using the Wilcoxon test. Paired student’s t-test was used
for comparison of TNF-α level before and after treat-
ment. A P-value less than 0.05 was considered statisti-
cally significant. Statistical package for social science
software (SPSS), used to analyze the data.
The study sample consisted of 21 women and 9 men
with a mean age of 50.7 ± 7.5 years (range 35 - 66 years)
and a total 112 lesions. The buccal mucosa was the most
common site (47%) for OLP, followed by gingiva (24%),
tongue (22%), labial mucosa (0.5%), and palate (0.2%).
Approximately 85% of the lesions showed partial to
complete clinical improvement at the end of the treat-
ment period, and the results were also persistent in the
three months follow-up period after drug therapy cessa-
tion (Table 1). 14% of LSs had no change, and one per-
son showed deterioration (Table 1). Analysis of Wil-
coxon test showed that there was a significant difference
F. Agha-Hosseini et al. / Open Journal of Stomatology 1 (2011) 13-17
Copyright © 2011 SciRes. OJST
in LS before and after treatment (P < 0.05) in the treat-
ment and follow up periods (Table 1). OLP clinical
scores decreased in almost all scoring groups. At the end
of treatment, 69% of patients showed complete to partial
SR (Table 2). A significant difference in SR was ob-
served before and after treatment (P < 0.05). Numeric
scale changes had significant improvement in all time
point assessment through the trial course (Table 2).
Following treatment, the level of TNF-α (pg/ml)
changed from 29.9 ± 6.6 to 39.7 ± 8.3 without statisti-
cally significant difference (P = 0.225) according to stu-
dent’s paired t-test (Figure 1).
The immunomodulatory mechanisms of IMOD are not
clearly understood, but it can increase CD4+ lymphocyte
count after 1 to 3 months treatment [12]. Its effect is also
preserved for a long period after treatment cessation. It
was primarily used in HIV infected patients, providing
amelioration of AIDS manifestations. It has passed 3
phases of clinical trial without any considerable adverse
effects. Considering the durability, safety and immu-
nologic effects, it could be used in treatment of immu-
nologic disorders [5]. Because of the immunologic na-
ture of OLP [3], use of IMOD as an immunoregulator
drug would appear reasonable for treatment outcome.
This is the first clinical trial that evaluates the efficacy
and compliance of this immunomodulator drug in OLP
In this study, erosive subtype changes from 45% of
total lesions at base line to 7% after treatment. 33% of
erosive lesions resolved completely, 20% converted to
reticular, 42% to atrophic < 1 cm and 5% only had size
reduction without subtype change. Converting erosive
form to another type of lesion (atrophic and reticular
form) with a decreased risk of malignant change can be
considered an important outcome of this investigation.
At the end of treatment, a significant improvement was
seen in lesion clinical scores. 85% of lesions showed
some degree of clinical improvement. In our recent study,
we have evaluated the therapeutic efficacy of antioxi-
dant- rich purslane (an herbal extract) on OLP lesions.
The results showed that approximately 83% of lesions
have been changed [11].
It was shown that in a randomized trial of pime-
crolimus 1% cream (as case group) versus triamcinolone
acetonide paste (control group) in OLP treatment, the
mean clinical score at the base line was 2.4, that decreased
Table 1. Clinical response.
Treatment period Follow up period
Clinical response 2 weeks % 1 month %2 months %3 months %4 months % 5 months % 6 months %
+5 (5 degrees improvement) 0 0 2 5 7 8 10
+4 (4 degrees improvement) 0 1 3 5 8 12 11
+3 (3 degrees improvement) 4 4 8 11 13 14 14
+2 (2 degrees improvement) 30 41 41 41 35 34 34
+1 (1 degree improvement) 19 18 26 23 23 20 17
0 (no change) 47 36 20 14 13 11 12
–4 (4 degrees worsening) 0 0 0 0 0 1 1
–5 (5 degrees worsening) 0 0 0 1 1 0 1
Median (range) +1 (0,3)* +1 (0,4)* +2 (0,5)* +2 (–5,5)* +2 (–5,5)* +2 (–4,5)* +2 (–5,5)*
P value 0.001 0.001 0.001 0.001 0.001 0.001 0.001
*Significant according to Wilcoxon test compared to before treatment (P < 0.05).
Table 2. Symptomatic response.
Treatment period Follow up period
Symptomatic response 2 weeks % 1 month %2 months %3 months %4 months % 5 months % 6 months %
+3 (3 degrees improvement) 0 7 10 10 10 10 10
+2 (1 degrees improvement) 7 14 7 7 7 7 7
+1 (1 degree improvement) 31 28 48 52 59 48 52
0 (no change) 59 48 35 31 24 35 31
–1 (1 degrees worsening) 3 3 0 0 0 0 0
Median (range) 0 (–1,2)* 0 (–1,3)* +1 (0, 3)* +1 (0, 3)* +1 (0, 3)* +1 (0, 3)* +1 (0, 3)*
P value 0.005 0.002 0.001 0.001 0.001 0.001 0.001
*Significant according to Wilcoxon test compared to before treatment (P < 0.05).
F. Agha-Hosseini et al. / Open Journal of Stomatology 1 (2011) 13-17
Copyright © 2011 SciRes. OJST
Figure 1. The unstimulated whole saliva concentration of
TNF-α (pg/ml) in baseline and end of the treatment with IM-
OD in patients with OLP; P < 0.05 was considered statistically
to 1.6 after two months of treatment [4]. Mean clinical
score before treatment in this study was 3.38, improving
to 1.55 at the end of the three month treatment period,
and 1.22 at the end of the follow-up period. It shows and
emphasizes the highly durable therapeutic effect of
IMOD after treatment cessation.
It was suggested methylene blue-mediated photody-
namic therapy may be as a possible alternative treatment
for OLP [13]. Thirteen persons with 26 lesions took part
in their study. At the end of treatment, despite 4 reticular
lesions, no complete remission was found in other scor-
ing groups. In this investigation 33% of erosive lesions
had complete remission and 20% converted to reticular
form. 57% of reticular lesions disappeared after the
treatment period. This shows the higher effectiveness of
IMOD rather than photodynamic therapy in management
of OLP lesion.
A downward shift of the numeric scale occurred in our
patients at the end of the treatment period. The results
were successfully preserved 3 months after treatment
cessation in the follow up period. One study evaluated
the efficacy of 0.1% dexamethasone oral rinse (3 times a
day for 6 weeks) for treatment of erosive OLP. VAS
(visual analog scale) value was decreased significantly at
the end of the treatment period, but they did not assess
the maintenance of treatment outcome in their study
group [14]. However, it has been reported that one third
of OLP patients treated with topical corticosteroids de-
velop secondary candidiasis [15].
Until recent years, corticosteroids have been the
mainstay of OLP treatment because of their an-
ti-inflamma- tory and immunosuppressive effects. Ac-
cording to some reports TNF-α may be a good index for
monitoring treat- ment response of corticosteroids, but
not in any other drug subtypes. The mechanism of cyto-
kine regulation by immunomodulator drugs has not been
identified. But they potently inhibit TNF-α production
by peripheral blood mononuclear cells, and enhance se-
cretion of IL-2 and INF-γ [16]. Despite significant im-
provement in patient symptoms and sign, no statistical
differences were found in TNF-α level before and after
treatment in this study. This finding may be explained by
the assumption that TNF-α may be involved in the im-
munopathogenesis of OLP. Increasing differentiated T
cell numbers after treatment by IMOD may be a possible
explanation of the slight upward shift of TNF-α level.
Despite the devastating effect of TNF-α, it has pri-
mary beneficial effects by initiation of inflammatory
response, promoting angiogenesis and reparative process
as well [10]. Corticosteroid drugs suppress both aspects
of this double-edged sword cytokine. But an immu-
noregulator drug such as IMOD just regulates its action
and promotes improvement in sign and symptom of OLP
lesion, without deletion of the TNF-α beneficial effect
that provides wound healing. It may be a possible ex-
planation for the slight but statistically unimportant in-
crease in TNF-α level after treatment with IMOD.
IMOD May be an efficacious choice of OLP treatment,
but further controlled studies required to elucidate its
real efficacy. TNF-α may not be a worthwhile tool in the
follow-up in this study. The relationship of TNF-α level
and other type 1 and type 2 cytokines in immunopatho-
genesis of OLP needs further study and may shed more
light on its pathogenesis.
[1] Ismail, S.B., Kumar, S.K. and Zain, R.B. (2007) Oral
lichen planus and lichenoid reactions: Etiopathogenesis,
diagnosis, management and malignant transformation.
Journal of Oral Sciences, 49, 89-106.
[2] Agha-Hosseini, F., Mirzaii-Dizgah, I., Mikaili, S. and
Abdollahi, M. (2009) Increased salivary lipid pero-
xidation in human subjects with oral lichen planus.
International Journal of Dental Hygiene, 7, 246-250.
[3] Greenberg S. (2008) Burket’s oral medicine. 11th Edition,
BC Decker Inc, Hamilton, 89-94.
[4] Gorouhi, F., Solhpour, A., Beitollahi, J.M., Afshar, S.,
Davari, P., Hashemi, P., Nassiri Kashani, M. and Firooz,
A. (2007) Randomized trial of pimecrolimus cream
versus triamcinolone acetonide paste in the treatment of
oral lichen planus. Journal of the American Academy of
Dermatology, 57, 806-813.
[5] Khairandish, P., Mohraz, M., Farzamfar, B., Abdollahi,
M., Shahhosseiny, M.H. and Madani, H. (2009)
Preclinical and phase 1 clinical safety of Setarud
(IMOD™), a novel immunomodulator. 17, 148-156.
[6] Zhang, Y., Lin, M., Zhang, S., Wang, Z., Jiang, L., Shen,
F. Agha-Hosseini et al. / Open Journal of Stomatology 1 (2011) 13-17
Copyright © 2011 SciRes. OJST
J., Bai, J., Gao, F., Zhou M. and Chen, Q. (2008)
NF-kappaB-dependent cytokines in saliva and serum
from patients with oral lichen planus: A study in an
ethnic. Chinese population Cytokine, 41, 144-149.
[7] Pezelj-Ribaric S., Prso, I.B., Abram, M., Glazar, I.,
Brumini, G. and Simunovic-Soskic, M. (2004) Salivary
levels of tumor necrosis factor-alpha in oral lichen planus.
Mediators of Inflammation, 13, 131-133.
[8] Banno, T., Gazel, A. and Blumenberg, M. (2004) Effects
of tumor necrosis factor-alpha (TNF alpha) in epidermal
keratinocytes revealed using global transcriptional pro-
filing. The Journal of Biological Chemistry, 279, 32633-
32642. doi:10.1074/jbc.M400642200
[9] van der Meij, E. H. and van der Waal, I. (2003) Lack of
clinicopathologic correlation in the diagnosis of oral
lichen planus based on the presently available diagnostic
criteria and suggestions for modifications. Journal of
Oral Pathology & Medicine, 32, 507-512.
[10] Thongprasom, K., Luangjarmekorn, L., Sererat T. and
Taweesap, W. (1992) Relative efficacy of fluocinolone
acetonide compared with triamcinolone acetonide in
treatment of oral lichen planus. Journal of Oral
Pathology & Medicine, 21, 456-458.
[11] Agha-Hosseini, F., Borhan-Mojabi, K., Monsef-Esfahani,
H.R., Mirzaii-Dizgah, I., Etemad-Moghadam S. and
Karagah, A. (2010) Efficacy of Purslane in the treatment
of oral lichen planus. Phytotherapy Research, 24,
[12] Mohraz, M., Khairandish, P., Kazerooni, P.A., Da-
varpanah, M.A., Shahhosseiny, M.H., Mahdavian, B.,
Vaziry, S., Shahriary, S., Kamali, K., Khorram Khorshid,
H.R., Heshmat, R., Farhadi M. and Gharibdoust, F. (2009)
A clinical trial on the efficacy of IMOD in AIDS patients.
17, 277-284.
[13] Aghahosseini, F., Arbabi-Kalati, F., Fashtami, L.A.,
Djavid, G.E., Fateh M. and Beitollahi, J.M., (2006)
Methylene blue-mediated photodynamic therapy: A
possible alternative treatment for oral lichen planus.
Lasers in Surgery and Medicine, 38, 33-38.
[14] Rhodus, N.L., Cheng, B., Bowles, W., Myers, S., Miller
L. and Ondrey, F. (2006) Proinflammatory cytokine
levels in saliva before and after treatment of (erosive)
oral lichen planus with dexamethasone. Oral Diseases,
12, 112-116. doi:10.1111/j.1601-0825.2005.01165.x
[15] Lodi, G., Tarozzi, M., Sardella, A., Demarosi, F., Cane-
gallo, L., Di Benedetto, D. and Carrassi, A. (2007)
Miconazole as adjuvant therapy for oral lichen planus: a
double-blind randomized controlled trial. British Journal
of Dermatology, 156, 1336-1341.
[16] Payvandi, F., Wu, L., Naziruddin, S.D., Haley, M.,
Parton, A., Schafer, P.H., Chen, R.S., Muller, G.W.,
Hughes, C.C. and Stirling, D.I. (2005) Immunomo-
dulatory drugs (IMiDs) increase the production of IL-2
from stimulated T cells by increasing PKC-theta
activation and enhancing the DNA-binding activity of
AP-1 but not NF-kappaB, OCT-1, or NF-AT. Journal of
Interferon & Cytokine Research, 25, 604-616.