A88: Tocilizumab: A Practical Experience From a North Indian Centre
Authors: Agarwal Manjari , Jariwala Mehul , Sawhney Sujata 
Published: March 2014

Background/Purpose:

In spite of a felt need, biologic use is restricted in India because of the prohibitive cost. Tocilizumab (TZ) has changed the outcome of children suffering from systemic onset juvenile idiopathic arthritis (SJIA). We cannot use TZ at the recommended schedule because of cost issues. We use it sparingly, at increased intervals and have such experience in 33 children.

To study use and safety of TZ in our study cohort

To analyze outcome of SJIA patients given TZ

To study factors affecting outcome

Methods:

Data prospectively collected on predesigned proforma for all children who received TZ from 01.03.2009 to date.

Results:

Demographics:

Age and Sex: 33 children (17 boys) identified

Diagnosis: 28 SOJIA; 2 Unclassifiable JIA; 1 ERA, 1 PJIA,1 Takayasu's aortoarteritis

Clinical details for SJIA:

Median age at diagnosis: 5 yrs (range 0.7–14)

Median age at commencing TZ 8.1 yrs (range 2.75–21.4)

Median duration of disease before commencing TZ 2.27 yrs (range 0.1–15.1)

Macrophage activation syndrome (MAS) was seen in 4 before commencing TZ.

Details of active joints and drugs, before and after TZ in Table .

Clinical parameters and medications prior to and after TZ

N=28
Prior to TZ
Current Status

Median swollen joints
4 (0–18)
0 (0–4)

Median swollen joints
4 (0–14)
0 (0–3)

NSAID
93%
0

Oral Steroid
100%
7%

Intravenous Steroid
71%
0

Methotrexate
85%
85%

HCQ
50%
21%

Leflunomide
14%
18%

Thalidomide
21%
0

Ciclosporin
14%
3%

Indications:

86% of children had both systemic and articular disease, 11% had only articular disease and 3% had persistent systemic features in isolation.

Dosing schedule:

The tapering schedule followed: 2 weekly till active systemic features; 3 weekly for 2 doses; 4 weekly for 2 doses; with clinical remission, dose tapered to 6 weekly and every 8 weeks before discontinuing.

Outcome of SOJIA patients on TZ:

296 doses administered in 28 patients.

Median time to response for systemic features 15 days (range 14–45)

Median time to response in articular disease 70 days (14–365).

65% of patients successfully tapered the medication (completely off to 8 weekly) and only 3 needed to re start because of a flare. Details of disease status in Table .

Disease status of SOJIA patients given TZ

Disease status
No. of children
Median no. of doses (range)
Median duration on Actemra(weeks)
Duration in remission (weeks)

Disease remission off TZ (Median duration 106 weeks)
12
7.5(3–24)
34(8–170)
113(49–192)

Disease remission on TZ 8 weekly
6
19(5–40)
98(16–195)
35(18–70)

Disease still active on TZ 4 weekly
6
8.5(5–12)
24(12–54)
NA

No response and flare of disease (after 2 to 6 doses)
2
3.5(3–4)
13(10–16)
NA

Lost to follow up
2
5.5(4–7)
29(14–44)
NA

Safety: A stringent prebiologic screening was done: Mantoux, CXR, HIV, Hepatitis B and C screening. Mantoux positive in 2, both latent TB. No child had immediate or delayed infusion reactions. 1 child had acute otitis media after 1st dose, 1 child had acute parotitis after 2nd dose, 4 children had persistent allergic rhinitis during the duration of TZ therapy. No mortality. Lipid profile monitored periodically; normal in all.

Factors affecting outcome: Univariate analysis did not reveal any factor for predicting response/flare.

Conclusion:

TZ has revolutionized the therapy of difficult to treat SOJIA. It is possible to taper the dose from once in 2 weeks to 8 weeks/or omit TZ in up to 65% of patients.