enca 2016 - genoa - tadej avcin
TRANSCRIPT
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JIA treatment protocols and transition experience in Slovenia
Tadej Avčin
University Children’s Hospital Ljubljana
Slovenia
ENCA meeting, PReS, Genoa, Sept 2016
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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
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Treat-to-target approach in the management of JIA
Aimed at achieving and maintaining clinical remission or, at least,
minimal disease activity
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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
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Management of JIA: a clinical guideBlazina Š, et al. Pediatr Drugs 2016 (in press)
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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Refractory JIA extended oligoarthritis with hip arthritis
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Subluxation leftwrist
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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
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Methotrexate – duration/discontinuation
• No uniform tapering strategy
• MTX withdrawal results in disease flare in >
50% of patients
– Even higher rate in younger children
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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
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Is remission forever?
• 40 – 70% of children that achieved clinical remission
on medication will have a disease flare within three
years off their medication
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Future perspective
• Individualized treatment:
– The Right Dose of
– The Right Drug for
– The Right Indication for
– The Right Patient at
– The Right Time
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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
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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
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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)
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“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
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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
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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
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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
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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
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“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
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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
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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
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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
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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
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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.