Download A Case Study in RA

Interactive Hot Topics Series
Implementing Treat to Target:
A Case Study in RA
MP-RA-0267
The Treat-to-Target Paradigm
Main
target
Adapt therapy
according to
disease activity*
(consider
comorbidities
and other
patient factors)
Active RA
Adapt therapy
if state is lost*
(consider
comorbidities
and other
patient factors)
Sustained
remission
Remission
Use a
composite measure
of disease activity every
1 ‒ 3 months
Assess
disease activity about
every 3 ‒ 6
months
Low disease
activity
Alternative
target
Adapt therapy
according to
disease activity*
(consider
comorbidities
and other
patient factors)
Adapt therapy
if state is lost*
(consider
comorbidities
and other
patient factors)
RA, rheumatoid arthritis
Reproduced from Smolen JS, et al. Ann Rheum Dis. 2016;75:3-15. © 2016, with permission from BMJ Publishing Group.
Sustained
low disease
activity
*Shared decision with patient
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Key Principles in Treating to Target
1. The primary target for treatment of RA should be a state of clinical remission
2. Clinical remission is defined as the absence of signs and symptoms of significant inflammatory disease
activity
3. While remission should be a clear target, based on available evidence, low disease activity (LDA) may be
an acceptable alternative therapeutic goal, particularly in established, long-standing disease
4. Until the desired treatment target is reached, drug therapy should be adjusted at least every 3 to 6
months
5. Measures of disease activity must be obtained and documented regularly, as frequently as monthly for
patients with high/moderate disease activity, or less frequently (such as every 3 to 6 months) for patients
in sustained low disease activity or remission
6. The use of validated composite measures of disease activity, which include joint assessments, is
needed in routine clinical practice to guide treatment decisions
7. Structural changes and functional impairment should be considered when making clinical decisions, in
addition to assessing composite measures of disease activity
8. The desired treatment target should be maintained throughout the remaining course of the disease
9. The choice of the (composite) measure of disease activity and the level of the target value may be
influenced by considerations of comorbidities, patient factors, and drug-related risks
10. The patient has to be appropriately informed about the treatment target and the strategy planned to reach
this target under the supervision of the rheumatologist
Treat to Target. 2015. Available at: http://www.t2t-ra.com/recommendations/target-to-treat-statements
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Treating to Target in Practice: Case Study*
 Bob is a 45-year-old carpenter
 He presents with a 5-month history of joint pain in his
hands, feet and knees and he also has morning
stiffness with a duration of 3-4 hours
* Hypothetical case; not based on actual patient
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Case Study: Assessment of Disease Activity
 Physical examination:
− 15 tender joints
− 13 swollen joints
− PtGA: 7.5/10
− EGA: 7.1/10
 Imaging:
− No erosions or joint space narrowing
 Laboratory values:
− ESR: 36 mm
− CRP: 4.2 mg/dL
− RF: negative
− Anti-CCP: 24 U
Anti-CCP, anti-cyclic citrullinated protein antibody; CRP, C-reactive protein; EGA, Evaluator’s Global Assessment; ESR, erythrocyte sedimentation rate;
PtGA, Patient’s Global Assessment; RF, rheumatoid factor
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Case Study
Question: What Composite Measure Would Be Suitable for
Assessment of Disease Severity in This Patient?






DAS-28?
SDAI?
CDAI?
RAPID3?
HAQ?
Other?
The CDAI for this patient = 42.6
(high disease activity)1,2
CDAI, Clinical Disease Activity Index; DAS-28, Disease Activity Scorse-28 joint; HAQ, Health Assessment Questionnaire; RAPID3,
Routine Assessment of Patient Index Data 3); SDAI, Simplified Disease Activity Index
1.
2.
Aletaha D, Smolen J Clin Exp Rheumatol. 2005;23(5 Suppl 39):S100-108.
Amercian College of Rheumatology. 2015. Available at: http://www.rheumatology.org/Portals/0/Files/CDAI%20Form.pdf
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Case Study: Initiation of Treatment
 The treatment goal for this patient is disease remission
as reflected by an CDAI score ≤2.8
 Treatment for Bob is initiated with:
− 15 mg/week oral MTX
− 1 mg/day folic acid (except on the day of MTX administration)
− 10 mg/day prednisone with a plan to taper and discontinue by 3
months
 Bob will be re-evaluated in 6 weeks
MTX, methotrexate; CDAI, Clinical Disease Activity Index
7
ACR Guidelines Support MTX As Initial Treatment
for Early RA
*
†
#
Consider adding low-dose
glucocorticoids (≤10 mg/day of
prednisone or equivalent) in
patients with moderate or high
RA disease activity when
starting disease-modifying
antirheumatic drugs
(DMARDs) and in patients with
DMARD failure or biologic
failure
Also consider using short-term
glucocorticoids (defined as <3
months treatment) for RA
disease flares. Glucocorticoids
should be used at the lowest
possible dose and for the
shortest possible duration to
provide the best benefit-risk
ratio for the patient
Treatment target should ideally
be low disease activity or
remission
Singh JA, et al. Arthritis Care Res. 2016;68:1-25. © 2015, American College of Rheumatology.
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Case Study: 6-week Follow-up
 Physical examination:
− 5 tender joints
− 3 swollen joints
− PtGA: 3.1/10
− EGA: 2.7/10
 Imaging:
− No erosions or joint space narrowing
 Laboratory values:
− ESR: 22 mm
− CRP: 2.6 mg/dL
− RF: negative
− Anti-CCP: 23 U
The CDAI for this patient = 13.8
(moderate disease activity and
a moderate response to
treatment)1
Anti-CCP, anti-cyclic citrullinated protein antibody; CRP, C-reactive protein; EGA, Evaluator’s Global Assessment; ESR, erythrocyte sedimentation rate;
PtGA, Patient’s Global Assessment; RF, rheumatoid factor
1. Smolen JS, Aletaha D. Clin Exp Rheumatol. 2014;32 (Suppl 85):S75-S79.
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Case Study: Question
 What changes in treatment might be appropriate for Bob?
−
−
−
−
Increase the oral MTX dose?
Add a second synthetic DMARD?
Switch to subcutaneously delivered MTX?
Switch to a biologic agent?
DMARD, disease-modifying antirheumatic drug; MTX, methotrexate
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Case Study: Augmentation of Treatment
 Treatment for Bob is changed to:
− 20 mg/week oral MTX
− 1 mg/day folic acid (except on the day of MTX administration)
− 5 mg/day prednisone with a plan to discontinue at the next visit
 Bob will be re-evaluated at 3 months after treatment
initiation
MTX, methotrexate
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Higher MTX Doses Are Associated
with Better Clinical Efficacy
 Systematic review of the literature on optimal dosage of MTX in patients with RA
 Starting doses of 25 mg/week or fast escalation with 5 mg/month to 25-30 mg/week
were associated with higher clinical effect sizes in comparison with doses of
5-15 mg/week or slow escalation
2.5
12.5–20 mg/week
5–10 mg/week
2.0
Placebo
Effect size
1.5
1.0
0.5
0
-0.5
-1.0
SJC
TJC
Pain
Global
RA, rheumatoid arthritis; SJC, swollen joint count; TJC, tender joint count
Reproduced from Visser K, van der Heijde D. Ann Rheum Dis. 2009;68:1094-1099. © 2009 with permission from BMJ Publishing Group.
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Case Study: 3-month Follow-up
 Physical examination:
− 3 tender joints
− 3 swollen joints
− PtGA: 2.6/10
− EGA: 2.3/10
− Bob also complains of nausea and mild abdominal pain
 Imaging:
− No evidence of structural lesions
 Laboratory values:
− ESR: 20 mm/hr
− CRP: 2.3 mg/dL
− RF: negative
The CDAI for this patient = 10.9
(moderate disease activity)1
− Anti-CCP: 24 U
Anti-CCP, anti-cyclic citrullinated protein antibody; CRP, C-reactive protein; EGA, Evaluator’s Global Assessment; ESR, erythrocyte sedimentation rate;
PtGA, Patient’s Global Assessment; RF, rheumatoid factor
1. Smolen JS, Aletaha D. Clin Exp Rheumatol. 2014;32 (Suppl 85):S75-S79.
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Case Study: Question
 What changes in treatment might be appropriate for Bob?
−
−
−
−
Increase the oral MTX dose?
Add a second synthetic DMARD?
Switch to subcutaneously delivered MTX?
Switch to a biologic agent?
DMARD, disease-modifying antirheumatic drug; MTX, methotrexate
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Case Study: Augmentation of Treatment
 Treatment for Bob is changed to:
− 25 mg/week MTX delivered by subcutaneous injection
− 1 mg/day folic acid (except on the day of MTX administration)
− Prednisone is discontinued
 Bob will be re-evaluated in 3 months
MTX, methotrexate
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SC Administration Improves MTX Bioavailability
 Single center, open
label, randomized,
2-period, 2-sequence,
single-dose crossover
study in 4 dose groups
(7.5 mg, 15 mg,
22.5 mg, and 30 mg)
with 54 healthy adults
MTX, methotrexate; SC, subcutaneous
Pichlmeier U, Heuer KU. Clin Exp Rheumatol. 2014 ;32:563-571.
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Improved GI Tolerability with SC vs Oral MTX
VAS Score (0-100)
P=0.015
MTX, methotrexate; SC, subcutaneous; VAS, visual analog scale
Adapted from Kromann CB, et al. J Dermatolog Treat. 2014;17:1-3.
P=0.047
P=0.002
N=37
P=0.053
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Significant Improvement of Disease Control
Following Switch From Oral to SC MTX
 Retrospective analysis
of 103 RA patients
switched from oral to
SC MTX:
P=0.006
− 40 switched due to
inadequate efficacy of
oral MTX
− 63 patients switched
due to GI side effects
of oral MTX
P=0.0001
MTX, methotrexate; SC, subcutaneous; DAS, disease activity score
Hameed B, Jones H. Int J Rheum Dis. 2010;13:e83-e84. © 2010 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.
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Case Study: 6-month Follow-up
 Physical examination:
− 1 tender joints
− 0 swollen joints
− PtGA: 0.5/10
− EGA: 0.7/10
− Nausea and mild abdominal pain have resolved
 Imaging:
− No erosions or joint space narrowing
 Laboratory values:
− ESR: 20 mm/hr
− CRP: 1.6 mg/dL
− RF: negative
− Anti-CCP: 24 U
The CDAI for this patient = 2.2
(low disease activity
approaching remission)1
Anti-CCP, anti-cyclic citrullinated protein antibody; CRP, C-reactive protein; EGA, Evaluator’s Global Assessment; ESR, erythrocyte sedimentation rate;
PtGA, Patient’s Global Assessment; RF, rheumatoid factor
1. Smolen JS, Aletaha D. Clin Exp Rheumatol. 2014;32 (Suppl 85):S75-S79.
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Case Study: Treatment
 Treatment for Bob:
− 25 mg/week MTX delivered by subcutaneous injection will be
continued
− 1 mg/day folic acid (except on the day of MTX administration)
 Bob will be re-evaluated in 3 months:
− If remission is sustained, current treatment will be continued. If
not, a further augmentation of therapy will be considered
MTX, methotrexate; SDAI, Simplified Disease Activity Index
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Summary: Multiple Steps in Treatment May Be
Needed to Achieve Goals
Initiate
Treatment
with Oral
MTX/Dose
Titration
Inadequate
Response/
Intolerance
Switch to
SC MTX
Clinical Remission
or LDA/Limited
Radiographic
Progression
One Approach to Treating to Target
SC, subcutaneous; LDA, low disease activity
Adapted from Yazici Y, Bata Y. Bulletin of the Hospital for Joint Diseases. 2013;71(Suppl 1):S46-48; Bykerk VP, et al. J Rheumatol.
2012;39:1559-1582; Alsaeedi S, Keystone EC. Nat Rev Rheumatol. Advance online publication 5 August 2014.
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