Better understanding of
pathogenesis of juvenile idiopathic arthritis (JIA) have led to the use
of a number of biological agents in last two decades [1]. Their high
cost and potential adverse effects preclude them from being used as
first-line agents in developing countries. Their most important adverse
effect is infection, and in India, tuberculosis is of particular concern
[2]. Aim of the present study was to evaluate the adverse events and
response to biological agents in patients with JIA, and to provide
description of challenges in way of treatment of JIA with biological
agents.
We conducted chart review of all patients diagnosed
to have JIA and treated with biological agents in our center. Diagnosis
of JIA was based on International League of Associations for
Rheumatology Criteria [3]. They were treated as per guidelines of
American College of Rheumatology [4]. Selected patients who were
refractory or had responded inadequately to conventional therapy, were
explained the need of biological therapy. It was prescribed on an
individual basis to those who could afford it. Screening for
tuberculosis was done before the initiation of therapy. Patients were
followed up every 4-12 weeks and the following information was extracted
from their records: demographic profile, clinical phenotype, laboratory
results, therapy, response and side effects. As available data might not
suffice for standard outcome criteria [5,6], response to treatment was
defined as complete response (no or minimal residual symptoms, with no
requirement for supplementary agents to maintain clinical remission and
normal laboratory study findings), no response (no or minimal clinical
benefit), and partial response (intermediate between remission and
absent response) [7].
Biological agents were given in 14 patients between
March 2012 – July 2015. Four patients were excluded because total
duration of follow up was less than 12 weeks in two, and discontinuation
of therapy (because of financial constraints) in two patients. Before
commencing biological agent, all 10 patients (7 males) were on disease
modifying antirheumatoid drugs (DMARDS), and 7 were on systemic
steroids. Mean (SD) age of study population at onset of disease and at
commencing biological agents was 4.8 (2.7) and 7.3 (3.6) years,
respectively. Median (range) duration of follow up following initiation
of biological agents was 11 (range 4-41) months. Clinical profile of the
patients who received biological agents are summarized in Table
I.
TABLE I Clinical Profile of Patients with Juvenile Idiopathic Arthritis Who Received Biological Agents
Age (y) at onset/
|
Type of disease |
Biological agent used* |
Outcome
|
Time to response (d)
|
at initiation of
|
|
|
|
Systemic |
Articular |
treatment
|
|
|
|
features |
features |
3.6 /4.2 |
Systemic onset |
Tocilizumab |
No response |
– |
–
|
|
|
Abatacept |
No response |
– |
– |
5/6 |
Systemic onset
|
Tocilizumab |
Partial response |
30 |
Still active
|
6/13.9 |
Polyarticular |
Etanercept |
Complete response |
- |
60 |
3/3.5 |
Systemic onset |
Tocilizumab |
Complete response |
15 |
30 |
10.6 /13 |
Polyarticular |
Etanercept |
Complete response |
- |
50 |
2/4.1 |
Systemic onset |
Tocilizumab |
Complete response |
15 |
30 |
7/8.3 |
Systemic onset |
Etanercept |
Complete response |
15 |
30 |
4/5.1 |
Polyarticular |
Etanercept |
Complete response |
- |
150 |
1/8 |
Systemic onset |
Tocilizumab |
Complete response |
20 |
90 |
6/7 |
Systemic onset |
Etanercept |
#Complete response |
7 |
30 |
*Doses of biological agent used: Tocilizumab 8 mg/kg/dose q 2
weeks, if <30kg 12 mg/kg/dose (IV infusion, dose tapered to 4
weeks with clinical response, Etanercept-0.8 mg/kg q wk SC,
Abatacept-10 mg/kg wk 0, 2, 4, then q 4 wk IV infusion; #Off
medication for 1 year. |
Clinical response was seen in nine out of 10
patients. Eight patients achieved complete response, while one had
partial response. Median (IQR) time to show response for systemic
features was 15 (15,20) days, and for articular disease was 40 (30,75)
days. Five out of 7 patients were free of steroids by three months. One
patient suffered from bronchopneumonia necessitating systemic
antibiotics, and another had minor reactions related to tocilizumab
infusion. No case of tuberculosis, malignancy or death occurred while on
treatment.
Experience with these agents in Indian patients is
scant. With biological agents, substantial proportion of patients were
able to discontinue systemic steroids. Efficacy to the biological agents
in published literature (75-85%) is comparable to the present study
[8-10]. Limitation of present set of data includes small number of
patients, lack of standardized outcome criteria due to retrospective
study design and use of biological agents in only those who could
afford. Two patients had to stop treatment due to high cost. We conclude
that biological agents can be used in children who fail conventional
treatment without risk of increased incidence of infection.
Contributors: IS: Data collection, analysis and
manuscript writing; LD: data collection and manuscript writing; NG: data
collection and manuscript writing; SKK: data collection, analysis,
manuscript writing, and will act as guarantor for the study
Funding: None; Competing Interests: None
stated
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