Session Information
Date: Sunday, November 8, 2015
Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects I: Juvenile Idiopathic Arthritis
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Gut microflora influences the development and homeostasis of the immune system. Dysbiosis has been reported in various immuno-inflammatory diseases. Pathogenesis of enthesitis-related-arthritis (ERA) category of JIA suggests an interaction between the gut and joints. Thus we studied the effect of probiotic therapy on immune and clinical parameters in children with ERA.
Methods: Forty-six children with active JIA-ERA were randomized to probiotic (VSL3 capsules) therapy or placebo along with NSAIDs for 12-weeks (CTRI/2012/08/002871). Patients, assessor and statistician were blinded to the allocation. Patients were assessed using a 6-point composite index of disease activity based on morning stiffness, joint count, enthesitis count, sacroilitis/inflammatory-back-pain, uveitis and ESR/CRP. Th1, Th2, Th17 and T-regulatory (Treg) cell frequencies were determined in blood using flow-cytometry. Cytokines IFNγ, IL4, IL17, IL10, TNFα and IL6 were measured in the serum by flow-cytometry using cytometric bead array (BD Biosciences) kit.
Results:
The average age of 46 children (44 boys) at enrollment was 15±2.5 year and duration of disease was 3.5±3 years. Most of the children were HLA-B27 positive (93.5%). All children had peripheral arthritis and 65% had associated enthesitis. 52% children had sacroilitis, 26% had inflammatory-back-pain, 9% had history of uveitis and 22% had a family member having spondyloarthritis.
There was no significant difference between the two groups at baseline. There were 2 dropouts in the probiotic-group while 4 in the placebo-group. There was a significant clinical response in both probiotic and placebo group after 12-weeks of therapy (Table) but probiotic group failed to show a significant clinical response compared to the placebo (Table). The immune parameters showed an increase in Th2 and IL-10 levels in placebo and a decrease in IL-6 with probiotics after 12 weeks (Table) but again the difference between the groups was significant only for IL10 levels (Table).
Adverse effects in the probiotic and the placebo groups were diarrhea (36 vs. 45%), abdominal pain (9 vs. 20%), minor infections (4.5 vs. 20%) and flatulence (23 vs. 15%) respectively. Two patients were withdrawn due to side effects 1 in placebo due to severe diarrhea and one in the probiotic-group due to tuberculosis.
Conclusion: Probiotic therapy in JIA-ERA children is well tolerated but failed to show any significant immunological or clinical effects over NSAID-therapy.
Table – Changes in Immune and clinical parameters in the probiotic (n=21) and the placebo groups (n=19). All values are expressed as median with interquartile range, *p<0.05, **p<0.01 represent significance in the same group after 12 weeks. CI-ESR and CI-CRP – Composite index based on ESR and CRP respectively, PGI – patient reported global improvement, EMS – early morning stiffness, TJC – tender joint count, SJC – swollen joint count)
|
|
Probiotic group (N=21) |
Placebo group (N=19) |
Difference between the groups (p values) Mann-Whitney test |
||||
|
|
Baseline |
After 12 weeks |
Median change |
Baseline |
After 12 weeks |
Median change |
|
|
Disease activity parameters |
|
||||||
|
CI-ESR |
3 (2-4.5) |
2 (1.5-4) |
-0.5 (-2 to 0)* |
3.5 (2.5-4) |
2 (1-2.5) |
-2 (-2.5 to -1)** |
0.06 |
|
CI-CRP |
3 (2.3-4.5) |
1.5 (1-4) |
-1 (-2.8 to 0)** |
3.5 (2.5-5) |
1.5 (0.5-2.5) |
-2 (-2.5 to -1.5)** |
0.16 |
|
PGI % |
– |
– |
70 (35 to 80) |
– |
– |
70 (25 to 90) |
0.8 |
|
EMS (min) |
30 (0-83) |
2 (0-18) |
-10 (-60 to 5)* |
45 (15-60) |
0 (0-15) |
-30 (-60 to 0) |
0.6 |
|
TJC (0-68) |
3 (2-5) |
1 (0-4) |
-1 (-3.5 to 1.5) |
3 (2-5) |
0 (0-1) |
-2 (-4 to -2)** |
0.06 |
|
SJC (0-66) |
2 (1.5-3.5) |
0 (0-1.5) |
-1 (-2.5 to -1)** |
2 (2-3) |
0 (0-1) |
-2 (-3 to -1)** |
0.15 |
|
Enthesitis count |
2 (0.5-4.5) |
2 (0.5-3.5) |
0 (-2 to 1.5) |
0 (0-3) |
1 (0-2) |
0 (0 to 2) |
0.5 |
|
ESR mm |
80 (39-120) |
42 (30-80) |
-15 (-61 to 10) |
80 (40-100) |
30 (22-45) |
-40 (-66 to 2) ** |
0.35 |
|
CRP mg/dl |
8 (2.4-10.4) |
0.7 (0.3-6) |
-3.3 (-8.3 to 0)* |
2.8 (1.4-6.8) |
1.1 (0.3-1.9) |
-1.5 (-4 to -0.2) ** |
0.36 |
|
Immune parameters |
|
|
|||||
|
Th1 % |
6.6 (4.9-8.9) |
7.0 (3.8-8.9) |
0.1 (-1.9 to 2.5) |
6.5 (3.3-9.3) |
5.9 (3.0-8.6) |
0.8 (-3.3 to 3.5) |
0.7 |
|
Th2 % |
0.6 (0.2-1.2) |
0.8 (0.3-1.5) |
0.2 (-0.2 to 0.6) |
0.3 (0.1-0.5) |
0.6 (0.3-1.7) |
0.3 (-0.1 to 1)* |
0.5 |
|
Th17 % |
1.5 (0.7-1.7) |
1.0 (0.4-1.8) |
-0.07 (-0.8 to 0.45) |
1.2 (0.7-1.8) |
1.2 (0.6-2.2) |
0.4 (-0.4 to 0.8) |
0.3 |
|
Treg % |
2.6 (1.8-3.4) |
2.6 (1.8-4.0) |
0.4 (-1.6 to 1.3) |
2.7 (1.3-3.7) |
3.2 (2.4-4.2) |
1.1 (-0.4 to 1.9) |
0.2 |
|
IL-6 pg/ml |
53 (12-15) |
11.4 (6.6-21) |
-37 (-102 to -1.7)* |
33 (21-127) |
13.5 (9-116) |
-9.2 (-40 to 16.8) |
0.13 |
|
TNFα pg/ml |
0.9 (0.4-2.8) |
0.41 (0-7.8) |
-0.75 (-2.3 to 0.5) |
1 (0.3-4.2) |
0.8 (0.2-1.6) |
0.14 (-2.2 to 0.9) |
0.5 |
|
IFNγ pg/ml |
0 (0-2.2) |
0 (0 -0) |
0 (-1.2 to 0) |
0 (0-2.4) |
0 (0-0) |
0 (-2.4 to 0) |
0.5 |
|
IL-4 pg/ml |
0 (0-0) |
0 (0 -1.64) |
0 (0 to 1) |
0 (0-1.85) |
0 (0-1.6) |
0 (-8.6 to 0.5) |
0.3 |
|
IL-17 pg/ml |
36 (2.7-58) |
34 (14-63) |
2.8 (-26 to 29) |
44 (20-62) |
24.3 (10-44) |
-20 (-42 to 6) |
0.26 |
|
IL-10 pg/ml |
1 (0.5-2.2) |
0.5 (0-1.35) |
-0.75 (-2 to 0.6) |
1.0 (0.7-1.6) |
2 (0-3.4) |
1 (-0.6 to 1.9)** |
0.013* |
To cite this abstract in AMA style:
Shukla A, Gaur P, Aggarwal A. Double Blind Placebo Controlled Randomized Trial of Probiotics in Enthesitis-Related-Arthritis Category of JIA: Effect on Clinical and Immunological Parameters [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/double-blind-placebo-controlled-randomized-trial-of-probiotics-in-enthesitis-related-arthritis-category-of-jia-effect-on-clinical-and-immunological-parameters/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/double-blind-placebo-controlled-randomized-trial-of-probiotics-in-enthesitis-related-arthritis-category-of-jia-effect-on-clinical-and-immunological-parameters/