7 Clinical Outcome Measures in Pediatric Rheumatic Diseases Flashcards
Core set of outcome measures of the ACR Pediatric 30 (6)
1) Physician global assessment of overall disease activity
2) Parent/patient global assessment of overall well-being
3) Physical functional ability, measured with an instrument validated in the pediatric population
4) Count of joints with active arthritis
5) Count of joints with restricted motion
6) Acute phase reactant
Gold standard for the assessment of response to therapy in JIA
ACR Pediatric 30
Using ACR Pediatric 30, patients are classified as responders in a clinical trial if
They demonstrate an improvement of at least 30% from baseline in at least 3/6 core set variables, with no more than 1 of the remaining variables worsening by more than 30%
ACR Pediatric 30 was adapted for use in clinical trials in sJIA by adding
Absence of spiking fever ≥38C during the week preceding the evaluation
Limitation of the JIA core set
Lack of input from patients or caregivers in its development
Independent initiative of international health professionals to update the core set and address the limitation of the ACR Pediatric 30
OMERACT
3-layered onion of the OMERACT
1) Inner layer: Domains mandatory for all clinical trials and observational studies
2) Middle layer: Optional domains
3) Outer layer: Domains for research purposes
Composite disease activity score currently used in JIA developed in 2009 and is an alternative approach to the ACR Pediatric 30
JADAS
Components of the JADAS
1) Physician’s global assessment of disease activity
2) Parent/patient global assessment of well-being
3) Count of joints with active disease
4) ESR or CRP
How is the physician’s global assessment of disease activity measured?
Measured on a 10-cm VAS where 0=no activity and 10=maximum activity
How is the parent/patient global assessment of well-being measured?
Measured on a 10-cm VAS where 0=very well and 10=very poor
Count of joint with active disease is assessed using
JADAS71 (71 joints)
JADAS27 (27 joints)
JADAS10 (10 joints)
ESR or CRP in JADAS is normalized using
0-10 scale
3-variable JADAS that does not include acute-phase reactant
cJADAS
Cutoff score for inactive disease using the JADAS and cJADAS for both poly- and oligoarticular JIA
≤1
Cutoff score for minimal/low disease activity for oligoarticular JIA using JADAS
≤2
Cutoff score for minimal/low disease activity for polyarticular JIA using JADAS
≤3.8
Cutoff score for minimal/low disease activity for oligoarticular JIA using cJADAS
≤1.5
Cutoff score for minimal/low disease activity for polyarticular JIA using cJADAS
≤2.5
The JADAS and cJADAS and respective cutoffs were validated only in children what categories of JIA
Poly- and oligoarticular
sJADAS specific to systemic JIA is composed of
4 items part of the original JADAS plus a 5th item, the systemic manifestation score, aimed to quantify the burden of systemic symptoms on a 0-10 scale
Components of the systemic manifestation score of sJADAS
1) Fever
2) Evanescent erythematous rash
3) Generalized LAD
4) Hepatomegaly and/or splenomegaly
5) Serositis
6) Anemia (hgb <9g/dL)
7) PC >600 or ferritin >500ng/mL
(1 point each except for fever, depends on temp)
Points for respective temps used in sJADAS
37-38C 1
38-39C 2
39-40C 3
>40 4
Damage in JIA is defined as
Persistent changes in anatomy, physiology, pathology, or function, which may be the consequence of previous active disease, side effects of therapy, or comorbid conditions, that is NOT due to currently active arthritis and is present for at least 6 months
2 components of JADI
JADI-A: Articular
JADI-E: Extraarticular
Score for joint damage used in JADI
0=no damage, 1=partial damage, 2=severe damage, ankylosis, prosthesis
Maximum total score for JADI
72
Components of the JADI-E (5)
1) Ocular
2) MSK non-articular
3) Cutaneous
4) Endocrine
5) Secondary amyloidosis
Components of the JSpADA (8)
1) Arthritis
2) Enthesitis
3) Patient pain rating
4) APR
5) Morning stiffness
6) Clinical sacroiliitis
7) Uveitis
8) Back mobility
T/F For JSpaDA, higher scores indicate greater disease activity
T
Considered the preferable lupus activity tool for use in routine clinical setting because it is concise and easy to complete
SLEDAI
Number of items in SLEDAI
24
SLEDAI version where rash, alopecia, mucous membrane lesions, and proteinuria are scored only if they represent their first occurrence or a recurrence (or a recent increase for proteinuria)
Original
SLEDAI version where items are simply scored when present
SLEDAI-2K
Advantage of MEX SLEDAI
avoiding the cost of immunological laboratory tests because it does not include anti–double-stranded DNA antibodies and complement levels
Definition of damage in SLE
any persistent nonreversible change in anatomy, physiology, pathology, or function, which may be the result of prior active disease, complications of therapy, or comorbid conditions, not related to active inflammation occurring since onset of SLE, ascertained by clinical assessment and present for at least 6 months;
Damage index used for adult SLE
SDI
Disadvantages of SDI
1) does not cover all forms of damage that are seen in children or adolescents with SLE, especially growth failure and delayed puberty
2) covers only irreversible damage and, therefore, does not take into account that children have the ability to recover and regenerate to a greater degree than do adults
Components of PED-SDI
12 systems/domains included in the original SDI + 2 items devoted to assessment of growth failure and pubertal delay
Based on the PRINTO core set of outcome variables for juvenile SLE, a “responder” is defined as
At least 50% improvement from baseline in 2/5 core set measures with no more than 1 of the remaining worsening by more than 30%
Damage occurring since diagnosis of systemic lupus erythematosus is ascertained by ___
Clinical assessment
Growth failure is defined as
At least two of the following three features:
(1) height below the third percentile for age
(2) growth velocity over 6 months below the third percentile for age, and
(3) crossing at least two percentiles (5%, 10%, 25%, 50%, 75%, 95%) on growth chart
Delayed puberty is defined as
A delay in development of secondary sexual characteristics more than 2 SD below the mean for age by Tanner staging
Among the criteria for flare of SLE, these are considered to be the most accurate
1) SLEDAI or BILAG
2) Physician global
3) C-reactive protein
4) MD-global
5) PCR
6) ESR
SLEDAI scores and interpretation
greater than or equal to
6.4/3.0/0.6 constituted major/moderate/minor flares, respectively
BILAG scores and interpretation
Greater than or equal to 7.4/3.7/2.2 delineated major/moderator/minor flares, respectively
Definition of ID (inactive disease)/CR (clinical remission) in cSLE that can differentiate from minimally active lupus (MAL)
1) Less than two mild, nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud phenomenon, chest pain, or objective physical signs of cSLE
2) ANA positivity and ESR elevation can be present
3) CBC, renal function testing, and complement C3 all must be normal
4) Only damage-related laboratory or clinical findings of cSLE can be coexistent with ID
Provisional criteria for clinically relevant improvement in children and adolescents with cSLE (ACR) which measures response to therapy
CHILI
CHILI score of___had high accuracy for identifying clinically relevant improvement
greater than 54
Most widely used method for muscle strength measurement in therapeutic trials
Manual muscle testing (MMT), based on the Medical Research Council (MRC) scale
MMT originally included the bilateral assessment of how many muscles
24
It has been shown that a subset of these 8 proximal, distal, and axial muscles (the so-called MMT8) tested unilaterally performs similarly to the entire set of 24 muscles and is more time- and cost-efficient
Neck flexors
deltoids (shoulder abduction)
biceps (forearm flexion)
wrist extensors
gluteus maximus (hip extension)
medius (hip abduction)
quadriceps (hip flexion)
ankle dorsiflexors
The most widely used muscle function instrument is
Childhood Myositis Assessment Scale (CMAS)
CMAS evaluates a combination of
muscle strength, muscle function, and endurance
How CMAS is done
performing 14 maneuvers and yields a numeric score out of a total of 52
CMAS is weighted toward what muscle groups
Lower extremity, proximal, and axial muscle groups
Core Sets of Outcome Measures for Juvenile Dermatomyositis
PRINTO Core Set
IMACS Core Set
2016 ACR Clinical Response Criteria
Items Included in Published Core Sets of Outcome Measures for Juvenile Dermatomyositis in general
1) Physician global
2) Parent global
3) Muscle strength
4) Functional ability
5) Lab assessment
6) HRQoL (PRINTO only)
7) Global disease activity tool (PRINTO and ACR only)
8) Extramuscular disease (IMACS only)
PRINTO criteria for clinically inactive JDM: state of inactive disease with or without therapy if
exhibits at least three of the following four criteria: creatine kinase less than or equal to 150 units/L, CMAS score greater than or equal to 48, MMT score greater than or equal to 78, and physician global assessment of disease activity less than or equal to 0.2 cm on a 0- to 10-cm VAS
Omitted from LOSI due to low interrater reliability
SA: extent of surface area involvement within each anatomical site
Sites assessed in mLOSSI (18)
Scalp/face, neck, chest, abdomen, upper back, lower back; right and left arm, forearm, hand, thigh, leg, foot
Domains assess in mLOSSI (3)
1) Degree of erythema at the edge of a lesion
2) Modified Rodnan skin thickness score
3) New lesions and/or enlargement of an existing lesion within the past month
mLOSSI possible score range
0-162
Composes the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT)
mLOSSI and LoSDI (Localized Scl Skin Damage Index)
Physician global assessment of disease activity
Physician global assessment of disease damage
LoSDI (Localized Scl Skin Damage Index) evaluates tissue damage as (3)
1) Dermal atrophy
2) Subcutaneous atrophy
3) Dyspigmentation (hypo/hyperpig)
Areas tested in the MRSS (17)
Right and Left: Fingers, hands, forearms, upper arms, thighs, legs, feet
Face, anterior chest, abdomen,
Scoring in MRSS
0 = normal skin, where the examiner appreciates fine wrinkles but no skin thickness is present;
1 = mild skin thickness, where the examiner can easily make skin folds between two fingers and fine wrinkles are acceptable;
2 = moderate skin thickness, with difficulty in making skin folds and no wrinkles;
3 = severe skin thickness, with inability to make skin folds between two examining fingers
preliminary disease severity score for juvenile systemic sclerosis (SS)
Juvenile Systemic Sclerosis Severity Score (J4S), includes nine organs/systems (general, vascular, skin, osteoartic- ular, muscle, gastrointestinal, respiratory, cardiac, and renal) and has a score range from 0 to 40
PVAS established by the pediatric vasculitis working party of PRES includes a set of items in how many organ systems
nine organs/systems:
systemic
cutaneous
mucous membranes/eyes
ear/ nose/throat
chest
cardiovascular
abdominal
renal
nervous
In addition to the damage score, the PVDI form assesses ___
school absences since the last evaluation
