JIA treatment protocols and transition experience in Slovenia

1. JIA treatment protocols and
transition experience in Slovenia
Tadej Avčin
University Children’s Hospital Ljubljana
Slovenia
ENCA meeting, PReS, Genoa, Sept 2016

2. 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

3. Treat-to-target approach in the management of JIA
 Aimed at achieving and maintaining clinical remission or, at least,
minimal disease activity

4. 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

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

8. General approach to JIA treatment
Oligo
NSAIDs
IA-CS
MTX
Poly
NSAIDs
Low PDN
MTX
Systemic
MP pulse i.v.
MTX
anti-IL1
anti-IL6
anti-TNFα
abatacept
anti-TNFα
abatacept
NSAIDs
High PDN

9. Second line drugs
Disease-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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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)

16. 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

17. Cervical spine involvement (UCHL cohort)
Semolič N, et al. Pediatr Rheumatol 2013; 11(Suppl 2): P96.
• 15 (3%) patients with cervical spine arthritis (clinical
and MRI)
– 3 patients as the initial manifestation of JIA
• All patients had LROM of cervical spine
• 12/15 (80%) patients had neck pain as initial
manifestation of the disease
→ All patients treated with anti-TNFα agents with good
clinical response and improvement of MRI features

19. Refractory JIA extended oligoarthritis with hip arthritis

21. Subluxation left
wrist

22. 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

23. Methotrexate – duration/discontinuation
• No uniform tapering strategy
• MTX withdrawal results in disease flare in >
50% of patients
– Even higher rate in younger children

24. 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

25. Is remission forever?
• 40 – 70% of children that achieved clinical remission
on medication will have a disease flare within three
years off their medication

26. Future perspective
• Individualized treatment:
– The Right Dose of
– The Right Drug for
– The Right Indication for
– The Right Patient at
– The Right Time

27. Transition
Blum 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

28. 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

29. 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)

30. “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

31. 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 educational
issues, assessment of “readiness”)
• Transfer Phase (18-19 years)
– Information exchange between pediatric and adult health care teams (telephone/email
contact, 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

32. 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

33. 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

34. 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

35. “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

36. 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

37. 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

39. 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

40. 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

44. 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.