Arun Gogna

Nitin Menon

Rajendra Sharma

S Y Kothari

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Journal of the association of physicians of india • vol 62 • published on 1st of every month 1st august, 2014 13
Comparison of Intra-articular Glucocorticoid 
Injections with DMARDs versus DMARDs alone in 
Rheumatoid Arthritis
Nitin Menon*, SY Kothari**, Arun Gogna***, Rajendra Sharma†
Introduction
Rheumatoid Arthritis, (RA) is the most common systemic autoimmune 
disease affecting 0.75% of the population, 
p r e d o m i n a n t l y  f e m a l e s ,  c a u s i n g 
inflammation, cartilage destruction 
and bony erosions in synovial joints.1-3 
Activation of T- Lymphocytes by an 
unknown antigen stimulates monocytes, 
macrophages and synovial fibroblasts 
to produce the cytokines interleukin 
(IL-1), IL-6 and tumor necrosis factor 
(TNF-α)  in the synovial fluid which 
in  turn  are  potent  s t imulators  o f 
*Formerly, Junior Resident, 
Dept. of Physical Medicine and 
Rehabilitation, **Spl. DGHS, 
MOHFW and Prof. Dept. of PMR, 
***Assoc. Prof., Dept. of Medicine, 
†Formerly Prof. and Head, Dept. 
of PMR, Safdarjang Hospital, 
New Delhi 110 029
Received; 21.11.2012; 
Revised: 15.04.2014; 
Accepted: 15.05.2014
Original article
mesenchymal cells such as synovial 
fibroblasts, osteoclasts and chondrocytes 
that release matrix metalloproteases 
(MMP).4,5 MMP in conjunction with 
elastases and proteases secreted by 
neutrophils degrade the cartilage and 
weaken it  which ultimately leading 
to joint destruction.4 Activated T-cells 
also cause an osteoprotegerin ligand 
(OPGL) mediated osteoclastogenesis and 
consequent bone loss.6
Early RA, which is characterized by 
joint swelling, stiffness and presence 
of inflammatory markers in the blood 
and synovium without radiographic 
Abstract
Background: Intra-articular triamcinolone in combination with DMARDs may be able to achieve faster 
and tighter control of disease activity in early rheumatoid arthritis that may be the key to preventing or 
minimizing later deformities. 
Objective: To compare the efficacy of a combination of  Disease Modifying Anti-Rheumatoid Drugs 
(DMARDs) with Intra-articular Glucocorticoids versus only DMARDs in a group of patients with early 
Rheumatoid Arthritis.(RA) 
Methods: Fifty patients diagnosed as Rheumatoid Arthritis (RA) by American Rheumatology Association 
(ARA) criteria (1987) with disease duration less than two years were randomized into two groups. The 
Control group received a combination of Methotrexate 15 mg daily with Sulfasalazine 2 gm daily for 3 
months and the Study group received the above combination along with Intra-articular injections of 
Triamcinolone acetate (40mg per ml) in each of the swollen joints at the start of the study. Outcome was 
assessed in terms of Disease Activity Score (DAS-28), American College of Rheumatology (ACR) 20/50/70 
criteria and number of rescue medications used at the end of 3 months.
Results: The study group had significant reductions in DAS 28 scores (3.39 versus 4.99 in control group) 
and significantly more subjects achieved the ACR 20/50/70 criteria at the end of 3 months (100/60/36% 
versus 84/20/0%) Secondary end-points like tender and swollen joint count, ESR, early morning stiffness, 
health assessment questionnaire (HAQ) scores and general health status were significantly reduced in the 
study group. Also, significantly lesser rescue medications were needed in the study group.
Conclusion: Combination of DMARDs with Intra-articular corticosteroids is significantly better than 
DMARDs alone in early RA.
© Japi • august 2014 • vol. 62   673
14 Journal of the association of physicians of india • vol 62 • published on 1st of every month 1st august, 2014
bony changes represents a therapeutic “window of 
opportunity”.7 Rapid control of  early inflammation 
may conceivably limit or prevent subsequent joint 
destruction or deformity. The older “pyramidal 
approach” to treatment has changed in recent years to 
achievement of remission with early use of DMARDs.8
Studies using corticosteroids in various forms 
have proven efficacy in retarding radiographic 
progression and achieving a tight control of the 
disease in combination with traditional DMARDs.9,10 
Triamcinolone is the least water soluble of all steroid 
preparations and tends to remain in the joint for long 
periods, thus producing its effects locally.11 Intra-
articular steroids impair the ability of monocytes to 
release TNF-α and suppress levels of other mediators 
like IL-1, IL-6 and IL-8.12,13  It also decreases levels of 
RANKL, a member of TNF-α family, thus leading to 
fewer erosions.14  Biologic DMARDs and intra-articular 
steroids are the only two agents acting on the RANKL/
OPGL and MMP systems, leading to greater bone and 
cartilage preserving effects.15
With this background in mind, we decided to 
design a study to assess the efficacy of a combination 
of intra-articular steroids with DMARDs versus 
DMARDs alone in early RA.
Materials and Methods 
Patients satisfying the American Rheumatology 
Association (ARA) 1987 criteria for diagnosis of RA 
aged over 18 years with disease duration less than 
two years and attending the Physical Medicine and 
Rehabilitation department of Safdarjang Hospital, 
New Delhi  were enrol led in this  prospect ive, 
randomized study which commenced in October 
2009 and ended in July 2011. The study was approved 
by the institution review board. After screening 
for exclusion criteria, written, informed consent 
was obtained and patients were randomized into 
two groups (control and study) by lots drawn. At 
baseline, Complete Blood Counts (CBC), Erythrocyte 
Sedimentation Rate (ESR), Liver and Kidney Function 
Tests, Rheumatoid Factor (RF), and radiographs of 
affected joints were performed. Number of Tender 
Joints (TJC), Swollen Joints (SJC), duration of early 
morning stiffness (EMS), patients assessment of pain 
and patients and physicians assessment of disease 
activity (VAS scale 0 to 100, 0=best, 100=worst) and 
Health Assessment Questionnaire (HAQ) modified in 
the Indian scenario was also recorded.
Study group received oral Methotrexate (MTX) 
15mg per week, oral Folic Acid 5 mg per day, (except 
on day of MTX administration) oral Sulfasalazine 
(SSZ) 2gm per day and intra-articular injections of 
Triamcinolone acetonide (40mg per ml) in each of 
the swollen joints (small joints of hand = 0.2 ml, 
wrist, elbow and ankle joints = 0.5 ml and knee and 
shoulder = 1 ml each) and Control group received 
oral MTX (15mg per week), oral folic acid (5mg per 
day, except on the day of MTX intake) and oral SSZ 
(2gm daily). Oral Diclofenac (50mg) was offered as 
rescue medication on an “as needed” basis. Subjects 
were followed up at 6 and 12 weeks and TJC, SJC, 
ESR, disease activity (as recorded by patient and 
physician), pain score and HAQ scores were recorded. 
In addition, CBC and LFT were done at each follow-
up. A count of oral NSAIDs used was maintained. 
Exclusion criteria were contraindications to steroids 
like Diabetes, acute infections, peptic ulcer disease and 
renal disease, joint deformity or erosions, treatment 
with oral or intra-articular steroids in the last one 
year, treatment with any other DMARD combination 
and pregnant and lactating women.
Disease Activity Score (DAS-28) and ACR20/50/70 
score at 12 weeks was considered as primary outcome 
measures. In addition, ESR, EMS, HAQ scores, TJC, 
SJC, general health status (patient reported on VAS 
scale 0 to 100, 0=best, 100=worst) and number of rescue 
medication tablets used were considered as secondary 
outcome variables. Data was managed on Microsoft 
Excel© and tested on SPSS for windows version 15 
software. Independent T test, Chi-Square test and 
Wilcoxon rank sum was used for data analysis. Results 
were considered significant at p<0.05.
Table 1 :  Baseline comparison between the two groups
Characteristics Control Group(n=25)
Study Group
(n=25) p-value
Demographic Characteristics
Age (in years) 37(Range 18-60)
37.36           
(Range18-64) 0.734
Sex (M:F) 3:22 3:22 1.000
Smokers 4(16%) 3(12%) 0.684
Disease Characteristics
Duration (in months) 14.44 13.24 0.575
Rheumatoid Factor 
Positive 13(52%) 18(72%) 0.145
Early Morning Stiffness
(in minutes) 81.6 80.4 0.404
ESR (mm) 47.32 42.68 0.13
Tender Joint Count 17.96 17.4 0.793
Swollen Joint Count 7.88 8.44 0.464
Health  Assessment 
Questionnaire (HAQ) 
scores
1.256 1.386 0.47
General Health Condition
(VAS on a scale from 0 to 
100, 100 being worst)
62.6 69 0.143
Disease Activity Score
(DAS 28) 6.631 6.65 0.977
p < 0.05 taken as statistically significant
674  © Japi • august 2014 • vol. 62
Journal of the association of physicians of india • vol 62 • published on 1st of every month 1st august, 2014 15
Results
In all, 56 patients were enrolled in the study out 
of which 50 completed 3 months follow-up. (25 in 
each group) There were 6 drop-outs (2 due to allergic 
reactions to SSZ, 3 due to lack of follow-up and one 
developed amenorrhea).
Baseline characteristics of both groups are summed 
up in Table 1.
The mean age of patients in the study group was 
37.36 years (range=18 to 60 years) and the control 
group was 37 years (range=18 to 64 years) with a 
female to male ratio of 22:3 in both groups. Three 
patients in the study group (12%) and 4 patients in 
the control group (16%) were smokers. The mean 
disease duration was 13.24 months in the study group 
(range=3 to 24 months) and 14.44 months (range=3 to 
24 months) in the control group. Eighteen patients 
(72%) were rheumatoid factor positive in the study 
group while it was 13 patients (52%) in the control 
group. Both groups were comparable in all baseline 
characteristics.
At the end of 6 and 12 weeks, significant reduction 
in all disease parameters was seen in the study 
group. (Table 2 and 3) Patients who received steroid 
injections with DMARDs showed an initial quick 
fall in all parameters which improved further at 12 
weeks. Patients who were treated with only DMARDs 
also improved in all parameters but did so, slowly in 
comparison to the study group across the duration 
of the study. 
We used an average dose of 340 mg of triamcinolone 
acetonide in  our  s tudy group.  (Range=80mg-
640mg) Injections were given with standard sterile 
precautions using anatomical landmarks for needle 
placement. Apart from giddiness and nausea in a few 
patients and pain during needle entry, there were no 
other side-effects during the injection procedure itself. 
A d ve r s e  e f f e c t s  i n  b o t h  g r o u p s  i n c l u d e d 
gastritis, mouth ulcers, acneiform lesions and skin 
hypopigmentation at injection sites in the study 
group which were all managed conservatively without 
dropping out from the study.
Discussion
The goal of treatment in RA is to achieve remission 
or low disease activity state.
Modern approach to treatment favours the “reverse 
pyramid” concept for achievement of this goal which 
entails starting with a combination of DMARDs with 
or without steroids and then tapering to maintenance 
levels or using biologic agents.8 
Both the groups in our study were comparable at 
baseline in all parameters. At the end of 6 weeks, the 
study group showed a significant improvement in 
both the primary and secondary outcome measures as 
compared to the control group. This effect was carried 
over till 12 weeks. This result is in agreement with a 
number of studies which showed significantly more 
improvement when a combination of DMARDs was 
used with local and oral steroids.10,16,17. 
ESR showed improvement in the study group 
which was significant at 6 weeks but not significant at 
12 weeks. This is because ESR has low discriminatory 
power and is a poor predictor of patient’s long term 
prognosis.18 Hence an improvement in ESR ought to 
be looked for rather than its absolute value. At 12 
weeks the DAS-28 score was 3.39 which indicates 
moderate disease activity. This is close to the low 
disease activity score (2.6 to 3.1) which is the aim 
of treatment.  Although significantly more patients 
achieved the ACR 20 and ACR 50 criteria in the study 
group, greater achievement of ACR 70 criteria in the 
study group (36% in the study group compared to 
0% in the control group) was considered as a highly 
desirable goal in the management of patients with 
RA. All the secondary end-points, that is tender joint 
count, swollen joint count, general health status scores 
and early morning stiffness showed significantly 
more improvement in the study group signifying 
across the board improvement when DMARDs were 
used with intra-articular steroids. Our study also 
showed significantly lower HAQ scores in the study 
Table 2 :  Primary and secondary end point variables at 6 
and 12 weeks
Parameters
At 6 Weeks At 12 Weeks
Control Study p-value Control Study p-value
ESR (mm/
hour)
39.68 
(±12.12)
28.32 
(±13.47)
0.004 32.68 
(±13.42)
26.6 
(±12.91)
0.134
Tender Joint 
Count
12.28 
(±5.56)
3.12 
(±3.56)
0.001 8.36 
(±4.8)
3 
(±3.14)
0.001
Swollen Joint 
Count
4 (±1.5) 0.36 
(±1.03)
0.001 3 (±1.25) 0.6 
(±2.08)
0.001
General 
Health Status 
(VAS 0 to 100)
51.8 
(±12.57)
30 
(±14.64)
0.001 42.4 
(±15.95)
27.8 
(±14.36)
0.002
DAS 28 scores 5.71 (±0.72)
3.48 
(±1.07)
0.001 4.99 
(±0.93)
3.39 
(±1.26)
0.001
p < 0.05 taken as statistically significant
Table 3 : Selected End Point Variables at 12 Weeks
Parameters Control Group Study Group p-value
Early Morning Stiffness 
(minutes) 40.8(±15.32) 13.6(±12.2) 0.001
Fall in HAQ scores 0.45(±0.31) 0.69(±0.34) 0.009
ACR 20 21(84%) 25(100%) 0.037
ACR 50 5(20%) 15(60%) 0.004
ACR 70 0 9(36%) 0.001
Rescue Medications 
(Diclofenac tablets) 43.84(±17.31) 14.4(±7.17) 0.001
p <0.05 taken as statistically significant
© Japi • august 2014 • vol. 62   675
16 Journal of the association of physicians of india • vol 62 • published on 1st of every month 1st august, 2014
group which entails a better functional outcome in 
these patients. We have used a validated modified 
HAQ for Indian population which focuses on tasks 
specific to our population.19 At the end of 12 weeks, 
the study group required significantly lesser rescue 
medication tablets thus lessening the cost of therapy 
and minimising potential risk of added side-effects.
We have come across several studies which have 
used various combinations of oral and/or intra-
articular steroids in RA but we have not come 
across any study with intra-articular triamcinolone 
acetonide. Triamcinolone was used in our study 
because of its property of staying in the joint for 
long periods and thus producing more local effects. 
The ideal agent to be used would be triamcinolone 
hexacetonide but it is not available in India and both 
the acetonide and hexacetonide compounds have 
similar fractions of systemic absorption. 
In conclusion, it can be stated that a combination of 
intra-articular steroids with DMARDs is significantly 
better than only DMARDs in controlling disease 
activity of patients with early RA. They might also turn 
out to be an effective alternative to more expensive 
options like biologic agents in achieving desired 
disease control. However, more studies especially 
those comparing biologics with combination of 
DMARDs and intra-articular steroids are needed to 
support this claim. 
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676  © Japi • august 2014 • vol. 62


Comparison of Intra-articular Glucocorticoid Injections with DMARDs versus DMARDs alone in Rheumatoid Arthritis

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Comparison of Intra-articular Glucocorticoid Injections with DMARDs versus DMARDs alone in Rheumatoid Arthritis

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