A REVIEW ON VARIOUS TREATMENT MODALITIES OF RHEUMATOID ARTHRITIS: A PERSPECTIVE STUDY

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A REVIEW ON VARIOUS TREATMENT MODALITIES OF RHEUMATOID ARTHRITIS:
A PERSPECTIVE STUDY
P Veeresh Babu *, V Soundarya
Department of Pharmacology, Gokaraju Rangaraju College of Pharmacy, Bachupally, Hyderabad, India
*Corresponding Author Email: pratap.veeresh@gmail.com
Article Received on: 27/11/18 Approved for publication: 19/01/19
DOI: 10.7897/2230-8407.100375
ABSTRACT
Rheumatoid arthritis is a systemic disease that causes progressive joint damage and disability. The macrophage is an important pathogenic mediator in
rheumatoid arthritis, and cytokines such as tumour necrosis factor alpha (TNFα) and interleukin-1 are therapeutic targets. Drugs that block TNF a
decrease joint inflammation and slow radiographic progression. There are various strategies for treatment of rheumatoid arthritis such as Allopathy,
Homeopathy, Ayurveda etc. In this review we discussed about the potency and side effects of various treatment approaches of RA. Allopathy is a first
line of treatment especially in acute conditions which provides both symptomatic and root cause relief. But it is supplemented with an array of side
effects which limits their use chronically. It can also be cured through Complementary and Alternative Medicine (CAM) like yoga, Ayurveda,
Naturopathy, Homeopathy, Unani, Siddha, acupuncture, etc. which has enough potential and remedial measures in treating arthritis. Home remedies,
preventions and precautions are also important aspects in minimizing the effect of arthritis.
Keywords: Rheumatoid arthritis, Allopathy, Complementary and Alternative Medicine (CAM), Interleukin-1, Tumour necrosis factor alpha (TNFα)
INTRODUCTION
Rheumatoid arthritis is a chronic, systemic, inflammatory,
autoimmune disease that causes progressive articular destruction
and associated co-morbidities in vascular, metabolic, bone, and
psychological domains. Rheumatoid arthritis affects about 1% of
the population, alongside 5 and 50 per 100,000 people newly
developing the condition each year, can present at any age, and is
more prevalent in women than in men. It is characterised
clinically by joint pain, stiffness, and swelling due to synovial
inflammation and effusion. By contrast with other forms of
arthritis, rheumatoid arthritis synovitis has a high propensity to
disobey tissue boundaries, infiltrating articular bone and cartilage
(then called pannus).The disease causes disability (with loss of
working capacity and early retirement) and premature death if
insufficiently treated.
The process is driven by antigen-presenting cells, T cells and B
cells that result in the expansion of inflammatory cytokines, such
as interleukin (IL)-1, IL-6 and TNF-α. It is identified that chronic
joint inflammation is induced by the activated T cells infiltrating
in the synovial membrane. T cells are activated by the antigen–
presenting cell, presenting the antigen to the T-cell receptor.
Activated T cells, in turn activate B cells either directly or via pro-
inflammatory mediators. These activated B cells then get
differentiated into antibody-producing plasma cells. The anti-
citrullinated C peptide (anti-CCP) and rheumatoid factor (RF)
antibodies form complexes to activate, attract and complement
other inflammatory cells to the synovium. Activated B cells also
produce a number of pro-inflammatory mediators including IL-1,
IL-21, IL-6, TNF-α, interferon gamma, and lymphotoxin. T cells
and B cells activate macrophages via pro- inflammatory
mediators. Macrophages produce TNF-α, IL-1, IL-6 and
interferon-γ. Dendritic cells produce IL-1, IL-6, TNF-α attracting
cell to the inflammatory cell infiltrating the synovium. In addition
to this, macrophages directly secrete matrix metalloproteinase
and other proteolytic enzymes damaging synovial tissue. A
cluster of cell types are drawn into the downstream effector
mechanisms like endothelial cells and synoviocytes undergoing
morphological changes and resulting in inflamed, synovial
hyperplasia leading to joint destruction and damage1-4.
Early diagnosis helps in preventing severe destruction of joint
tissue but is difficult to accomplish. Diagnosis of RA depends on
the symptoms and some blood tests can also help to confirm RA.
1. C-reactive protein test (CRP)- show inflammation and
activity of the disease
2. Cyclic Citrullinated Peptide Antibody (CCP)
3. Erythrocyte Sedimentation Rate (ESR) - show
inflammation in the body.
4. Ultrasound or MRI
5. Joint X-rays
6. Synovial fluid analysis
7. Complete Blood Count (CBC)-evaluate and monitor
complication of RBC and WBC.
8. Rheumatoid factor (RF) – used to help diagnose RA.
The management of rheumatoid arthritis is a multidisciplinary
approach in order to lessen the pain, reduction of inflammation
and restoration of joints function.

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VARIOUS TREATMENT STRATEGIES FOR
RHEUMATOID ARTHRITIS
Allopathy
It is a conventional treatment in which drugs are used to cure
acute and life-threatening illness or infections. It is scientifically
proved system of medicine and most widely followed one. But it
is associated with many untoward effects which limits its usage
for some chronic conditions. In spite of these drawbacks it still
occupies the first place as far as treatment is concerned.
NSAIDs are particularly helpful during the first few weeks in
which a patient has symptoms, because the drugs provide partial
relief of pain and stiffness. NSAIDs should be used together with
DMARDs. NSAIDs exert their actions by inhibiting enzymatic
activity of the COX enzymes. Aspirin, ibuprofen, or naproxen are
non-steroidal anti-inflammatory drugs (NSAIDs) that can relieve
arthritis pain5.
Gold therapy has been shown to attenuate the destructive process
in RA, until the introduction of Methotrexates precursor,
aminopterin. Gold compounds were the standard for RA
treatment.
T cells also have an important role in rheumatoid arthritis. A
fusion protein — cytotoxic T-lymphocyte–associated antigen 4–
IgG1 (CTLA4Ig) binds to CD80 and CD86 on antigen-presenting
cells, blocking the engagement of CD28 on T cells and preventing
T-cell activation and is a promising new therapy for rheumatoid
arthritis. Combination of CTLA4Ig and methotrexate improved
the signs and symptoms of disease, physical function, and quality
of life in patients who had active rheumatoid arthritis despite
ongoing methotrexate therapy6.
Corticosteroids are potent suppressors of the inflammatory
response in rheumatoid arthritis. Predictable side effects of
corticosteroid drugs include thinning of the skin, cataracts,
osteoporosis, hypertension, and hyperlipidaemia 7,8.
Optimal management of rheumatoid arthritis requires rapid and
sustained suppression of inflammation with DMARDs, which are
defined as medications that retard or halt the progression of
disease. Disease modification is most convincingly demonstrated
by the ability of the medications to decrease radiographic
progression. DMARD is applied to medications which can alter
the course of disease and thus prevent joint erosion. The
mechanisms through which DMARDs act are varied but a
collective outcome is to help stem the destructive process of
intertwined inflammatory cascades resulting in the degradation of
soft tissue, cartilage and bone.
DMARDs have a delayed onset of action, whereas
glucocorticoids relieve signs and symptoms within days, appear
to have some disease-modifying potential.
Methotrexate is thought to be multifactorial, with inhibition of
cell maturation and to show reduce TNF levels in synovial tissue
of patients. It is now the drug of choice to maintain remission.
Three biologic products that inhibit the actions of TNF-α
(infliximab, etanercept, and adalimumab) and one that inhibits the
action of interleukin-1 (anakinra) and to treat rheumatoid arthritis.
The biologics used in inflammatory arthritis are genetically
engineered proteins derived from human genes. They mainly
inhibit specific components of the immune system that play
pivotal roles in driving or inhibiting inflammation in arthritis9.
The modern treatment strategy for RA involves early and highly
effective treatment with frequent clinical follow-up (tight control)
aiming at reaching a target of clinical remission in patients with
early RA and to achieve a target of low disease activity in patients
with long-standing RA. This, so called treat to-target strategy has
been shown to inhibit joint inflammation, preventing progressive
joint damage and future functional loss.
Quinine derivatives such as chloroquine and hydroxychloroquine
are very safe to use. They are used commonly in the treatment of
RA, but efficacy has not been demonstrated to be comparable to
Methotrexate10.
Sulphasalazine has anti-inflammatory and antimicrobial effects
and is suitable for mono- or combination therapy with e.g.
hydroxychloroquinine and MTX11.
Cyclosporine is mainly used in low-dose in combination with
MTX and reduces radiographic progression. It acts via T
lymphocytes, which are considered to be central in the
pathogenesis of early RA.
Leflunomide blocks pyrimidine synthesis. Its clinical and
radiographic effects match those of MTX.
Modern treatment strategies aim at reducing inflammation and
halting erosive damage.
Homeopathy
Homeopathy is effective in reducing the symptoms of joint
inflammation in RA. There was a significant improvement in
subjective pain, articular index, stiffness and grip strength in
those patients receiving homoeopathic remedies12.
Eg: Arnica, Nux vomica, Arsenicum album, Opium, Bryonia
alba, Pulsatilla Calcarea carbonica, Rhododendron, Causticum,
Rhustoxicodendron, Ignatia ruta, Lachesis, Sepia, Lycopodium
sulphur, Morgan, Sycotic co, Natrum muriaticum, Thuja are
homeopathic Remedies of wide action in rheumatoid arthritis13.
a) Arnica may help to soothe arthritic pain when applied
externally to areas of inflammation and soreness14.
b) It has known to show significant reduction in swelling and
pain and some of the active ingredients of Boswellia
(boswellic acids) have shown good anti-inflammatory
effects15.
c) Bryonia is an excellent remedy in cases of acute pains of
rheumatoid arthritis. Causticum that is used in homeopathic
treatment of individuals suffering from rheumatoid arthritis
has symptoms that include the development of deformities
in the joints, contractures and weakness in the muscles of the
body in general16.
d) Calcarea fluoricum medicine works for these patients of
arthritis who tend to have large or medium joint infections
such as knee joint, spine or shoulders17.
e) Rhododendron basically helps with rheumatic and
symptoms. It prevents stiffness of neck, pain in shoulders,
arms, wrists. It also provides relief of swollen joints and
gouty inflammation of the great-toe joint18.
Naturopathy
Herbal medicinal drugs that interact with the mediators of
inflammation are used in the treatment of rheumatoid arthritis
(RA). Herbal remedies can form an alternative source to relieve
symptoms in patients having RA as well as to address the

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drawbacks associated with present treatment methods with
allopathic drugs.
a) The antiarthritic property of Aloe vera is due to the
anthraquinone compound. It stimulates the immune system
and it is an anti-inflammatory agent19,20,21.
b) Oral administration of Withania somnifera Linn., root
powder showed the antiarthritic effect in adjuvant induced
arthritic rats22,23.
c) Extract of Boswellia serrata have natural anti-inflammatory
activities at sites where chronic inflammation is present by
switching off pro-inflammatory cytokines and mediators
which initiates the process. Boswellia serrata Linn., reduces
the breakdown of glycosaminoglycan synthesis24,25,26.
d) Piperine isolated from black pepper decreases the arthritic
symptoms27,28.
e) Black cohosh decreases the inflammation produced due to
the arthritis29,30.
f) Ginger extract is one of the effective arthritis joint pain
remedies recommended by physicians. Main constituents are
sesquiterpenoids, with (-) zingiberine. Sesquiterpene
Lactones (SLs) are natural products responsible for its anti-
inflammatory activity31,32.
g) Curcumin, a natural compound present in the rhizomes of
plant Curcuma longa, demonstrated its anti-inflammatory
action. Curcuminoids inhibits joint inflammation in both the
acute and chronic phase of arthritis33,34,35.
h) Hydro-alcoholic extract of Terminalia chebula Retz., shows
the anti-arthritic activity in formaldehyde or Complete
Freund's Adjuvant (CFA) induced arthritis. The anti-arthritic
activity of Terminalia chebula Retz., is due to its modulatory
effect on pro-inflammatory cytokine expression in the
synovium36.
Ayurveda
Ayurveda is very systemic and considered to be the best Indian
system of Medicine, having more approachable ways of
treatment. According to Ayurveda, RA is caused due to an
imbalanced Vata Dosha (Airy Bioelement) that leads to the
accumulation of Ama (toxin) in the body.
The classical ayurvedic formulation treatment includes several
pharmacological forms of internal herbal medicines [Arishtams
(Alcoholic preparations), Bhasmas (Ash), Choornas (Powder),
Grithams (Medicated Ghee), Gulikas (Tablet) Lehyams (Herbal
Jam), Kashayams (Water Extract) and Thailams (Oil)] which
eliminates the toxins and retaining back to the balance to
VataDosha (Airy Bioelement) in the body37,38.
The concept of Ayurveda suggesting the production of ama or
impaired metabolism invites the attention of researchers of to
combat the disease by eliminate this causative factor as such the
treatment. According to Ayurveda in addition to alleviation of
disease it also aims at augmenting the process of digestion both
at intestinal and cellular level.
Ayurvedic treatment (Ashwagandha powder and Sidh
Makardhwaj) has a potential to be used for the treatment of
rheumatoid arthritis39. A formula comprising B. serrata, T.
cordifolia, W. somnifera, and Z. officinalis patented for treating
RA and osteoarthritis 46.
Unani
As per Unani conventional and literal explanations, arthritis is
defined as the pain which occurs in different joints of the body
especially in the joints of arms and legs etc.40,41, 6-11 and the
description of disease is based on the four-humor doctrine of
Unani Medicine. The pathological changes in the joints are
caused mainly by derangement of temperament of humors, which
leads to accumulation of morbid materials into the joint spaces40,
42, 43,44. The pain in the joints is sometimes accompanied by with
or without swelling. The morbid materials develop contractures
also. Hippocrates says that the chronic illness like arthritis arises
from the accumulation of toxic materials. The principal of
treatment of arthritis is ‘tanqiya’ i.e., cleansing and evacuating of
morbid materials out of the body through munzijwamus’ hil
(concoctive and purgative) drugs which help correct deranged
temperament 44 by the complex process of detoxification 45. The
mode of action of concoctive and purgative drugs may be
detoxification and excretion of morbid materials out of the body.
Tanqiya is a complex process in the body by which the morbid
and diseased materials are taken out of the body by way of
evacuation, a complex phenomenon under certain environmental
conditions under vigil of a physician with the help of various
simple Unani drugs having munzij and mus'hil (concoctive and
purgative) effects under a very specific set of Unani guidelines
(Unani principles for this complex process) for a certain period of
time depending upon the chronicity, nature of the disease and type
of khilt (humor) involved therein.
It has analgesic and anti-inflammatory effects. It could also be
due to the anti-oxidant and energizing effects of the drugs which
maintain a balance between the formation of free radicals and
their utilization in the body or elimination from the body by the
complex mechanism of concoction and purgation since free
radicals are responsible for the development of RA. It helps in
keeping a correct balance between the formation of free radicals
and their utilization within the body. The treatment helps in
bringing pH level of urine from 4(higher acidic) to 6.5(nearly
alkaline) which is indicative of the fact that it had facilitated the
morbid materials to be excreted out of the body thus providing a
near balance of pH inside the body because a balance of pH is
must for the maintenance of health.
This medication acting as anti-oxidant must be reducing the level
of oxidative stress and acting as scavengers to mop out the free
radicals from the body leading to the stress-free state to the
already loaded damaged tissues and muscles of the joints in RA
thus maintaining near balance pH in the body and of course in the
urine. A number of gut induced toxins including endo-toxins (cell
wall compounds of bacteria, by-products of bacteria, candida
albicans, and yeast compounds) are also evacuated out due to
purgation 46 thus bringing a balance of pH inside the body free of
diseases.
The medication acting as anti-oxidants must be reducing the level
of oxidative stress and acting as scavengers to mop out the free
radicals from the body leading to the stress-free state in the body
including urine and it is here that free radicals are acting as
morbid materials which disturb the pH of the body also of urine.
It is also possible that the test formulation had helped in keeping
a correct balance between the formation of free radicals and their
utilization within the body that is why a considerable balance of
pH inside the body had been maintained.
Siddha Formulation
Interestingly, the Siddha system of treatment is being increasingly
recognized as an alternate approach to arthritic treatment. Herbal
mixtures have long been used in traditional medicine because of

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the synergism that takes place among the phytochemicals on the
herbs utilized.
A significant increase is observed in the activities of
glycohydrolases in RA. Furthermore recently a strong association
was found between RA and -d-glucuronidase and N-acetyl- -d-
glucosaminidase activities that were reported to be the foremost
glycosidases of stimulated chondrocyte supernatants and RA
sera47,48.
The increased activities of these lysosomal enzymes RA might
result in the degradation of proteoglycans and subsequently might
lead to the loss of collagen 49. This decrease in the level of
collagen might be due to declined collagen synthesis
accompanied by an increase in the catabolism of newly formed
collagen in acute phase and soluble to insoluble collagen in
chronic phase of the arthritis50.
HA (hyaluronic acid), a large glycosaminoglycan is a
predominant component of the articular surface. The most
probable mechanism of depletion of GAGs from matrix by -d-
glucuronidase and N-acetyl- -d-glucosaminidase is the
degradation of hyaluronate supplemented with the removal of
terminal monosaccharides of GAGs such as CS, resulting in the
decreased level of GAGs and its constituents. The decreased level
of hyaluronic acid in arthritic condition might also be due to
cleavage by hyaluronidases, since the catabolic contribution of -
d-glucuronidase and N-acetyl-d-glucosaminidase was reported to
be restricted to hydrolyze the oligosaccharides produced by the
action of hyaluronidase restoration of hyaluronic acid to normal
level by the treatment. By this it might have inhibited the
destruction of cartilage, bone and synovial tissue via regulating
the expressions of proinflammatory cytokines (TNF-α and IL-1)
59 and downregulating the chemical mediators such as
arachidonic acid 51 and PGE2 52,53. This results in the
downregualtion of MMPs (MMP-1) and increases the production
of TIMPs (TIMP-1) 53, consequently resulting in the increased
synthesis of collagen 55and proteoglycans 54,56,57 by the treatment.
It can even act via directly downregulating the expression of
MMPs (Unpublished data) and reducing the release of lysosomal
enzymes could reduce the degradation of cartilage, bone and
synovial tissue, thereby enhancing the increased synthesis of
collagen and GAGs. The drugs might have exerted their effect by
inhibiting lipid peroxidation, reducing the ROS/RNS 58,66and
enhancing the antioxidant system and via suppressing the
proinflammatory cytokines TNF- and IL-1 59 and reducing PGE2
synthesis 67,68, causing the increased stability of lysosomes.
Cell Therapy
MSCs (mesenchymal stem cells) and their role in hematopoiesis
and immune modulation suggests their potential use for cell
therapy.
A single intraperitoneal injection of allogeneic MSCs given at the
moment of immunization with CII (type II collagen), was
sufficient to prevent the occurrence of bone and cartilage erosions
in the joints of immunized mice. Current therapy for RA is
directed toward diminishing the inflammatory response and
treating the sequelae of uncontrolled inflammation. It represents
an effective new therapeutic approach to target the pathogenic
mechanism of autoimmune arthritis using adult stem cells59,60
Acupuncture
Acupuncture needles are inserted into the skin at specific points
along meridians or channels. It has been used for the relief of pain
that is caused by osteoarthritis of the knee. This can be severe and
maybe incompletely relieved by conventional treatments.
Although the best current evidence suggests that acupuncture
relieves pain, because it is an unusually potent placebo, it is safe
and can be considered as an adjunct to conventional treatment61
Yoga for Arthritis
Yoga is a comprehensive, multidimensional approach used to
improve health conditions. It has been used for reducing various
musculoskeletal problems, 62including rheumatoid arthritis. Yoga
plays an important role in improving physical, mental, emotional,
and spiritual well-being, as well as in managing stress and its
effects63.
a) Loosening exercises (Shithilikaranavyayama; 6 minutes)—
Passive rotation of the toes, toe bending, ankle rotation, knee
rotation, knee cap tightening, full butterfly, waist rotation,
hip rotation, shoulder rotation, neck bending, and neck
rotation.
b) Diaphragmatic breathing (3 minutes)
c) Strengthening exercises (Shakti Vikasaka Vyayama;4
minutes)
For the wrist-Mani Bandha Shakti Vikasaka
For the palms-Kara Tala Shakti Vikasaka
For the fingers-Anguli Shakti Vikasaka
For the elbows-Kaphoni Shakti Vikasaka
For the arms-Bhuja Bandha Shakti Vikasaka
For the back-Kati Shakti Vikasaka
For the thighs-Jangha Shakti Vikasaka
For the calf muscles-Pindali Shakti Vikasaka
d) Physical postures (Yogasan as 10 minutes)
Standing postures-ArdhakatiChakrasana, ArdhaChakrasana,
and Pada Hastasana
Prone postures-Bhujangasan andShalabhasana
Supine postures-Sarvangasana and Matsyasana
Sitting postures-Vakrasana and Ushtrasana
Shavasana with deep relaxation-7 minutes
e) Breathing practices (Pranayama; 11 minutes)
Preparatory practices-Kapalabhati Kriya and Vibhagiya
Pranayama
Pranayama-Surya AnulomaViloma, NadiShuddhi, Shitali,
Shitakari, and Sadanta
f) Meditation (Dhyana; 8 minutes)-Nadanusandhana and OM
meditation
g) Devotional song and silence (Bhajans; 5 minutes) 64.
Surgery and other treatments
In some cases, surgery may be done if other treatments have not
worked. This may include arthroplasty to rebuild the joint, joint
replacement, such as a total knee joint replacement65
CONCLUSION
Rheumatoid arthritis is a devastating condition of joints with
pandemic distribution. It adversely affects the quality of life with
high morbidity. Various treatment strategies are available to
control the problem but coupled with their own drawbacks.
Hence, early diagnosis associated with appropriate choice of
treatment helps in ameliorating the disorder.

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Cite this article as:
P Veeresh Babu & V Soundarya. A review on various treatment
modalities of rheumatoid arthritis: A perspective study. Int. Res.
J. Pharm. 2019;10(3):36-41 http://dx.doi.org/10.7897/2230-
8407.100375
Source of support: Nil, Conflict of interest: None Declared
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