The National Centre For Paediatric Rheumatology (NCPR) Experience of the Use of Tocilizumab (Ro-Actemra) in the treatment of Juvenile Idiopathic Arthritis ( JIA ): A 7-Year Story
Madan WA, Foley C, Lang C , Killeen OG, MacDermott E.
National Centre For Paediatric Rheumatology (NCPR), Our Lady’s Children’s Hospital (OLCHC), Dublin, Republic of Ireland.
Tocilizumab ( TCZ ) is a recombinant-humanised- monoclonal- antibody that acts as interleukin-6-receptor antagonist. Approved for treatment of children over 2 years with Systemic-onset JIA ( SJIA) and Poly-articular JIA ( PJIA ). Since 2010, TCZ has been used in the NCPR for these indications.
The aim is to describe to-date NCPR experience of the use of TCZ, and reports on outcomes, efficacy and tolerability.
A retrospective chart review of all children with JIA who received TCZ since its NCPR introduction in 2010. Baseline demographics recorded. Subtype of JIA documented. Prior and adjunctive treatments particularly oral steroids recorded. Completion of Pre-TCZ biologic workup reviewed.
TCZ dose and infusion frequency documented. Active disease was defined by active joint count (AJC), and/or presence of raised Acute Phase Reactants (APR). At TCZ commencement Initial AJC and raised APR documented.
Clinical remission defined by achievement of 0 AJC and Laboratory Remission defined by normalisation of APR. Outcome measures included clinical remission rate, laboratory remission rate, time to clinical remission and successful steroid wean.
A total of 32 JIA patients (81% Females) have been treated with TCZ over the past 7 years. The majority (41%) were SoJIA, 34% PJIA (3/11 RF-positive), 12.5% Extended OligoJIA (EoJIA), 6.25% Enthesitis-Related Arthritis (ERA) and 6.25% were Psoriatic JIA (PsJIA) . Median age at diagnosis 5.7yr (1.8-12.5yrs), median age at TCZ commencement 10 yrs and Median time to commencing TCZ 4.3 yrs ( 0.9-10.4yrs ).
Prior to TCZ, 97% of children received Methotrexate ( MTX ) monotherapy. Following MTX, Majority (91%) received at least two Biologics, 6% received four. Overall, Etanercept was most commonly used followed by Adalinumab.
All children had a full biologic prescreening prior to TCZ. All had negative TB screen and 97% were varicella immune. All received TCZ fortnightly at the outset with a dose of 12mg/kg if weight <30kg and 8mg/kg if weight >30kg.
Escalation to weekly infusions was required in 28% (9/32), 56% SoJIA. Adjuvant steroids were required in 56% at commencement of TCZ. Complete steroid wean was achieved in 83%. Average Initial AJC was 9 (3-23joints) and APR were raised in 56%. Clinical Remission achieved in 83% (25/30) and average time to remission was 5 months (0.5-16 mo). APR normalised in 78% after one infusion, 100% after three.
As a long term outcome, TCZ was continued in 78% (25/32), 36% (9/25) achieved and maintained reduced infusion frequency (3-8weekly). TCZ was discontinued in 22% (7/32), 3 of these children had primary loss of response and underwent stem cell transplant (HSCT), the remaining 4 had secondary loss of response and were switched to another biologic ( Rituximab, Ustekinumab, Adalinumab & Golimumab).
The outcome of TCZ is variable in different JIA subtypes with best results observed in PJIA and EoJIA with 100% remission rate and 100% continuation rate.
NCPR experience with TCZ has been positive, with high rates of remission (83%) and tolerability, 78% remaining on the drug. TCZ Improved Outcomes and Steroid Sparing in Refractory Cases. Rather than using multiple biologics, this encourages consideration of the drug earlier.