JIA treatment protocols and transition experience in Slovenia

Tadej Avčin

University Children’s Hospital Ljubljana

Slovenia

ENCA meeting, PReS, Genoa, Sept 2016

Clinical questions in the management of JIA

• Monitoring of disease activity & treatment goals

• Management strategies / Indications for treatment

• Features of poor prognosis

• Duration / discontinuation of therapy

• Long-term disease course

Treat-to-target approach in the management of JIA

Aimed at achieving and maintaining clinical remission or, at least,

minimal disease activity

Management of JIA

• Combination of

– Pharmacological interventions

– Physical and occupational therapy

– Psychosocial support

• A multidisciplinary, interactive and committed, specialized team

• The concept of patient-centred care

– Focus of the delivery of care on the patient

– The patient and their family active participants in decisions regarding

management

Management of JIA: a clinical guideBlazina Š, et al. Pediatr Drugs 2016 (in press)

General approach to JIA treatment

Oligo

NSAIDs

IA-CS

MTX

Poly

NSAIDsLow PDN

MTX

Systemic

MP pulse i.v.MTX

anti-IL1anti-IL6

anti-TNFαabatacept

anti-TNFαabatacept

NSAIDsHigh PDN

Second line drugsDisease-Modifying Antirheumatic Drugs (DMARDs)

• Drugs that slow down disease progression

– Decrease inflammation and/or suppress immune response

– Reduce or prevent joint damage

→ Help control arthritis but do not cure the disease

• Take effect over weeks or months

– Do not provide immediate relief of symptoms

Indications for treatment – Second line drugs

• Oligoarticular disease:

– Unresponsive disease to initial treatment with NSAID

and/or intraarticular injections of corticosteroid

• Polyarticular disease:

– Unresponsive disease to initial treatment with NSAID

and/or multiple intraarticular injections of CS

– Initial treatment as a corticosteroid sparing agent

Methotrexate

• The most commonly used DMARD for JIA

• Significant intra- and interindividual variability in the

absorption after oral administration

– Compared with IV dosing average oral bioavailability 0.7

• 35-45% of JIA patients fail to respond to MTX therapy

• MTX efficacy in different JIA subtypes

– Most effective in extended oligo- and polyarthritis

– Less effective in systemic JIA

116 JIA patients; mean F/u 80 months

MTX treatment efficacy – UCHL cohort

Inactive disease 76 (65%)

Mean time to inactive disease 4.7 m

Remission on MTX 51 (43%)

Mean time to 1st remission on th 8.8 m

MTX therapy in the era of biologics

Need for early identification of patients who will respond to MTX

compared to those who will require therapy with biologics

Treatment of JIA over time

1900 1920 1940 1960 1980 2000

Aspirin Gold Cortisone Methotrexate

NSAID’s

Leflunomide

Cox-2

Etanercept

Adalimumab

Infliximab

Anakinra

Abatacept

Tocilizumab

Rituximab

Canakinumab

Indications for treatment – Biologics

• Inadequate response to MTX or intolerance to

MTX

• Before or concurrent with MTX in severe JIA

– Cervical spine involvement

– Hip joint involvement

– Joint destruction (radiographic damage)

Patient cohort (UCH Ljubljana)

• > 200 patients treated with MTX

• 176 patients treated with biologic drugs

– anti-TNF: etanercept 61, adalimumab 48, infliximab 32

– tocilizumab 14

– rituximab 6

– anakinra 9

– canakinumab 4

– abatacept 2

Cervical spine involvement (UCHL cohort)Semolič N, et al. Pediatr Rheumatol 2013; 11(Suppl 2): P96.

• 15 (3%) patients with cervical spine arthritis (clinicaland MRI)

– 3 patients as the initial manifestation of JIA

• All patients had LROM of cervical spine

• 12/15 (80%) patients had neck pain as initialmanifestation of the disease

→ All patients treated with anti-TNFα agents with goodclinical response and improvement of MRI features

Refractory JIA extended oligoarthritis with hip arthritis

Subluxation leftwrist

Clinical questions in the management of JIA

• Monitoring of disease activity & treatment goals

• Management strategies / Indications for treatment

• Features of poor prognosis

• Duration / discontinuation of therapy

• Long-term disease course

Methotrexate – duration/discontinuation

• No uniform tapering strategy

• MTX withdrawal results in disease flare in >

50% of patients

– Even higher rate in younger children

Biologics – duration/discontinuation

• Treatment should last as long as the disease persists

• Disease duration unpredictable

• Treatment is only withdrawn completely after

prolonged and complete disease remission

– At least 24 months of clinically, immunologically and

radiologically inactive disease

Is remission forever?

• 40 – 70% of children that achieved clinical remission

on medication will have a disease flare within three

years off their medication

Future perspective

• Individualized treatment:

– The Right Dose of

– The Right Drug for

– The Right Indication for

– The Right Patient at

– The Right Time

TransitionBlum RW et al. J Adolesc Health 1993; 14: 570-6.

• Planned movement of adolescents and young adults with

chronic condition from child-centered to adult-oriented health-

care systems

– Age and developmentally appropriate

– Culturally appropriate

• Transfer: administrative event

Why is transition process needed?Selvaag AM, et al. Ann Rheum Dis 2014; Vidqvist KL et al. Rheumatology 2013.

• Pediatric rheumatic and musculoskeletal diseases (RMD) not

confined to childhood

– 50% of pediatric patients with RMD enter adulthood with

active disease and/or disease-related sequelae

– These patients need continuous, developmentally appropriate

care beyond adolescence

• 50% of patients do not make a successful transfer to adult

rheumatology (Hazel, Pediatr Rheumatol 2010)

– Particular high risk group of an unfavourable outcome

When to start transitional care?

• Childhood-onset disease: transition should start by early

adolescence (10-13 years) or 14 years at the latest

• Adolescent-onset disease (>14 years): transition should

start at the time of diagnosis

→ Transition process continues from early adolescence (10-13

years) through to late adolescence (17-19 years), ends in

young adulthood (20-24 years)

“Flexibility” of transition process

• Heterogeneity of adolescent developmental processes

• Potential impact of chronic illness on developmental

processes

– Patients with JIA may have delay in physical growth, psychosexual,

social and vocational developmental milestones

• Cultural differences

• Accommodate regional and national policies and laws

→ No firm timelines

Transition process UCH Lj

• Introductory Phase (14-16 years)

• Preparation Phase (16-18 years)

– Adolescent communication with doctor (medical issues)

– Adolescent communication with transition coordinator (psychosocial and educationalissues, assessment of “readiness”)

• Transfer Phase (18-19 years)

– Information exchange between pediatric and adult health care teams (telephone/emailcontact, transfer letter/medical summary)

– The young person have choice of who to be transferred to

• Post-transfer evaluation (3-6 mo after the first visit at adult rheumatology)

– Follow up visit at pediatric rheumatology clinic

– Assessment of adult rheumatology service

Transition programme UCH Lj

• Age at transfer

– Generally 18 - 19 years (the year of graduation from high school)

• Postponed transfer:

– Disease flare

– School problems

– Developmental delay

• Earlier transfer:

– Pregnancy

Transition programme UCH Lj

• Documentation:

– Documented transition plan

– Transfer letter /medical summary

• Transition coordinator: psychologist

• Adult service:

– UMC Ljubljana

– UMC Maribor

• Training of medical staff, patients and parents/caregivers

Transfer process (Handover)

• The adult and pediatric rheumatology teams have

direct contact as a minimum by telephone or email

before the handover

• Transfer documentation written ahead of the first

consultation with adult rheumatology

– Any confidential information included in a separate letter

• The first appointment with adult rheumatology should

be within 3 months of the summary being received

“Confidential information” in the transfer letter

• Possible sensitive issues:

– non-compliance

– induced abortions

– difficult psychosocial situation

– psychiatric problems

– substance abuse

→ Sent directly to adult rheumatologist as a separate letter

Training of the medical staff

• Departmental clinical practice points to consider on transition

– How to assess adolescents knowledge and skills

– How to prepare medical summary/transfer letter

→ Particuarly helpful for pediatric residents and fellows

• Transition education on pre-graduate and post-graduate level

– Medical students: part of pediatric curriculum at the Medical faculty in

Ljubljana

– Pediatricians: part of pediatric residency training programme, pediatric

society meetings and congresses

– Adult rheumatologists: part of rheumatology training programme, city-wide

clinical conferences, rheumatology society meetings and congresses

Training of patients and parents

• Individual communication at every clinic visit

• Information flyers (medical condition, coping strategies, healthy diet,

schoool issues, social benefits)

• Family educational days organized once yearly at the UCH Ljubljana

(organized in collaboration with Society for children with immune

diseases)

– Presentations available at patients society website: www.imuno.si

• Patient and parent educational programme during 2 weeks

balneorehabilitation at thermal spa Dolenjske toplice

Transition difficulties I.

• Adult rheumatology

– Long waiting time for the first appointment in the adult

rheumatology clinic

– Lack of knowledge (complications of JIA, treatment of

uveitis, vaccination status, school issues)

– No established pathway for feedback information from

adult rheumatologist

Transition difficulties II.

• Patients

– Nonadherence (particularly patients with inactive disease on

treatment)

– Lost to follow-up (adolescent “risky” behaviour)

– School issues (gym classes, coping strategies)

– Difficult to engage patients to become actively involved in

developing transition programme

• Health insurance

– Patients > 18 years if not studying at the University or unemployed

Acknowledgements

• University Children’s Hospital

Ljubljana

– Miha Kosmač

– Nataša Toplak

• Blood Transfusion Center of

Slovenia

– Vladka Čurin-Šerbec

• Anna Meyer Children’s

Hospital, Florence

– Rolando Cimaz

– Gabriele Simonini

– Ilaria Pagnini

Supported by grants L3-0624 and L3-4150

from The Slovenian Research Agency.