Guidelines in Rheumatology

Август 1, 2022

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Guidelines in Rheumatology

Содержание

2. Genetic Predisposition for Development of Ankylosing Spondylitis (AS) AS and HLA-B27 – strong association Ethnic and
3. Natural History of AS Highly variable Early stages: spontaneous remissions and exacerbations Spectrum of severity Mild
4. Burden of Illness Functional disability Potential complications Quality-of-life issues Pain, stiffness, fatigue, sleep problems Healthcare costs
5. Obstacles to Desirable Outcomes in AS Until Recently Diagnostic and classification limitations Lack of universally accepted
6. Advances in Medicine: Hope for Patients With AS Increased understanding of pathophysiologic processes Advent of Anti-TNF
7. Pathogenesis of AS Incompletely understood, but knowledge increasing Interaction between HLA-B27 and T-cell response Increased concentration
8. Clinical Features of AS
9. Modified New York Criteria for the Diagnosis of AS Clinical Criteria Low back pain, > 3
10. Disease Activity Assessment BASFI = Bath Ankylosing Spondylitis Functional Index BASDAI = Bath Ankylosing Spondylitis Disease
11. Bath Ankylosing Spondylitis Functional Index (BASFI) Visual analog scale (VAS) – 10 cm Mean score of
12. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) A self-administered instrument (using 10-cm horizontal visual analog scales)
13. ASsessment in Ankylosing Spondylitis (ASAS) ASAS 20: An improvement of > 20% and absolute improvement of
14. Introduction of Anti-TNF Agents for the Treatment of Ankylosing Spondylitis US Modifications of the ASAS International
15. Tumor Necrosis Factor: Functions of the Proinflammatory Cytokine Stimulation of endothelial cells to express adhesion molecules
16. Pathogenesis of Joint Destruction Bone Erosions Macrophages Endothelium Synoviocytes ↑ Proinflammatory cytokines ↑ Chemokines ↑ Adhesion
17. US Modifications of the ASAS International Guidelines: Appropriate Patients for Anti-TNF Therapy Definitive AS according to
18. Contraindications for Anti-TNF Therapy Current or recurrent infections Tuberculosis Multiple sclerosis Lupus Malignancy Pregnant or lactating
19. Monitoring and Discontinuing Treatment With Anti-TNF Agents ASAS core set of outcome parameters to monitor patients
20. Anti-TNF Agents Etanercept Approved in the United States and Europe for treatment of AS Dose: 50
21. Etanercept Vs. Infliximab: Pharmacologic Characteristics
22. Etanercept vs Infliximab: Clinical Differences Etanercept Approved by FDA for treatment of psoriatic arthritis, rheumatoid arthritis,
23. Etanercept for the Treatment of AS: Clinical Trials Marzo-Ortega, et al. Significant improvement in all clinical
24. Etanercept for the Treatment of AS: Clinical Trials (cont) Brandt, et al. 57% etanercept-treated patients and
25. Etanercept: Adverse Events *P
26. Etanercept: Adverse Events (cont) Serious infections and sepsis Mainly in patients with underlying illness or receiving
27. Infliximab for the Treatment of AS: Clinical Trials Brandt, et al. ≥ 50% improvement on outcome
28. Infliximab for the Treatment of AS: Clinical Trials (cont) Stone, et al. Improvement of > 60%
29. Infliximab: Adverse Events * Approximation based on all clinical studies
30. Infliximab: Adverse Events (cont) Serious infections and sepsis Cases in patients on concomitant immunosuppressive therapy Neurologic
31. Anti-TNF Agents: Summary Anti-TNF agents target underlying inflammatory process Alter disease progression Provide symptomatic relief Recommended
32. AS Treatment Algorithm: Patients with Axial AS Alternative Options Pamidronate Thalidomide *Only biologic approved for treatment
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Слайд 2

Genetic Predisposition for Development of Ankylosing Spondylitis (AS)
AS and HLA-B27 –

strong association
Ethnic and racial variability in presence and expression of HLA-B27

Слайд 3

Natural History of AS
Highly variable
Early stages: spontaneous remissions and exacerbations
Spectrum of

severity
Mild with limited sacroiliac or lumbar joint involvement to severe, debilitating disease
“Pre-spondylitic” phase – unrecognized period of progressive structural damage over a 5-to-10-year period
Average delay in diagnosis is 8.9 years

Слайд 4

Burden of Illness
Functional disability
Potential complications
Quality-of-life issues
Pain, stiffness, fatigue, sleep problems
Healthcare costs

= $6720 annually
75% indirect medical costs
Missed workdays
Limited-activity days

Слайд 5

Obstacles to Desirable Outcomes in AS Until Recently
Diagnostic and classification limitations
Lack

of universally accepted instruments to assess AS
Until recently, limited treatment options
NSAIDs, COX-2 inhibitors, DMARDs
Mostly symptomatic relief only
Minimal impact on natural course of disease

Слайд 6

Advances in Medicine: Hope for Patients With AS
Increased understanding of pathophysiologic processes

Advent of Anti-TNF agents
International meetings by ASAS (ASsessment in AS working group) to address need for universal standards
Development of ASAS guidelines
US modifications to the ASAS International Guidelines to meet realities of clinical practice in the United States

Слайд 7

Pathogenesis of AS
Incompletely understood, but knowledge increasing
Interaction between HLA-B27 and T-cell

response
Increased concentration of T-cells, macrophages, and proinflammatory cytokines
Role of TNF
Inflammatory reactions ? produce hallmarks of disease

Слайд 8

Clinical Features of AS

Слайд 9

Modified New York Criteria for the Diagnosis of AS
Clinical Criteria
Low back

pain, > 3 months, improved by exercise, not relieved by rest
Limitation of lumbar spine motion, sagittal and frontal planes
Limitation of chest expansion relative to normal values for age and sex

Radiologic Criteria
Sacroiliitis grade ≥ 2 bilaterally or grade 3 – 4 unilaterally
Grading
Definite AS if radiologic criterion present plus at least one clinical criteria
Probable AS if:
Three clinical criterion
Radiologic criterion present, but no signs or symptoms satisfy clinical criteria

Слайд 10

Disease Activity Assessment
BASFI = Bath Ankylosing Spondylitis Functional Index
BASDAI = Bath

Ankylosing Spondylitis Disease Activity Index
ASAS - IC = ASsessment in Ankylosing Spondylitis Improvement Criteria

Слайд 11

Bath Ankylosing Spondylitis Functional Index (BASFI)
Visual analog scale (VAS) – 10

cm
Mean score of 10 questions
Questions level of functional disability, including:
Ability to bend at the waist and perform tasks
Looking over your shoulder without turning your body
Standing unsupported for 10 minutes without discomfort
Rising from a seated position without the use of an aid
Exercising and performing strenuous activity
Performing daily activities of living
Climbing 12 to 15 steps without aid

Слайд 12

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
A self-administered instrument (using 10-cm

horizontal visual analog scales) that comprises 6 questions: Over the last one week, how would you describe the overall level of:
Fatigue/tiredness
AS spinal (back, neck) or hip pain
Pain/swelling in joints other than above
Level of discomfort from tender areas
Morning stiffness from the time you awake
How long does morning stiffness last?

Слайд 13

ASsessment in Ankylosing Spondylitis (ASAS)
ASAS 20: An improvement of > 20%

and absolute improvement of > 10 units on a 0–100 scale in > 3 of the following 4 domains:
Patient global assessment (by VAS global assessment)
Pain assessment (the average of VAS total and nocturnal pain scores)
Function (represented by BASFI)
Inflammation (the average of the BASDAI’s last two VAS concerning morning stiffness intensity and duration)
Absence of deterioration in the potential remaining domain
(deterioration is defined as > 20% worsening)

Слайд 14

Introduction of Anti-TNF Agents for the Treatment of Ankylosing Spondylitis
US Modifications

of the ASAS International Guidelines for Use of Anti-TNF Agents

Слайд 15

Tumor Necrosis Factor: Functions of the Proinflammatory Cytokine
Stimulation of endothelial cells

to express adhesion molecules
Recruitment of white blood cells in inflamed synovium and skin
Induction of inflammatory cytokine production (e.g., IL-1, IL-6)
Stimulation of synovial cells to release collagenases
Induction of bone and cartilage resorption
Stimulation of fibroblast proliferation

Слайд 16

Pathogenesis of Joint Destruction
Bone Erosions
Macrophages
Endothelium
Synoviocytes
↑ Proinflammatory cytokines
↑ Chemokines
↑ Adhesion molecules
↑

Metalloproteinase synthesis

Articular Cartilage
Degradation

Increased Cell Infiltration

Increased
Inflammation

Osteoclast
progenitors

↑ RANKL expression

TNF

Слайд 17

US Modifications of the ASAS International Guidelines: Appropriate Patients for Anti-TNF

Therapy

Definitive AS according to Modified New York Criteria
Active disease for ≥ 4 weeks
BASDAI > 4 cm at two times, 1 month apart
Physician Global Assessment ≥ 2 on Likert Scale
Treatment Failures
All types AS – lack of response/intolerability > 2 NSAIDs for ≥ 3 months
Patients with peripheral arthritis – lack of response/intolerability to > 1 DMARD, sulfasalazine preferred

Слайд 18

Contraindications for Anti-TNF Therapy
Current or recurrent infections
Tuberculosis
Multiple sclerosis
Lupus
Malignancy
Pregnant or lactating

Слайд 19

Monitoring and Discontinuing Treatment With Anti-TNF Agents
ASAS core set of outcome

parameters to monitor patients
Physical function, pain, spinal mobility, patient’s global assessment, stiffness, peripheral joints and entheses, acute phase reactant, fatigue
Assess at 6 to 8 weeks and discontinue patients who do not meet response criteria
BASDAI: Reduction of ≥ 2 units and
Physician Global Assessment > 1

Слайд 20

Anti-TNF Agents
Etanercept
Approved in the United States and Europe for treatment of

AS
Dose: 50 mg SC per week as two 25 mg injections administered on same day or 3 to 4 days apart
Infliximab
Approved in Europe for treatment of AS
Dose: 5 mg/kg IV at week 0, 2, and 6 and every 6 to 8 weeks thereafter

Слайд 21

Etanercept Vs. Infliximab: Pharmacologic Characteristics

Слайд 22

Etanercept vs Infliximab: Clinical Differences
Etanercept
Approved by FDA for treatment of psoriatic arthritis,

rheumatoid arthritis, juvenile rheumatoid arthritis, and AS
Infliximab
Approved by FDA for treatment of Crohn’s disease and rheumatoid arthritis
Safety
Tuberculosis and histoplasmosis
Post-marketing reports and FDA surveillance database indicate disproportionate association between infliximab and risk of such (opportunistic) infections

Слайд 23

Etanercept for the Treatment of AS: Clinical Trials
Marzo-Ortega, et al.
Significant

improvement in all clinical and functional parameters with etanercept treatment
86% MRI-detected entheseal lesions regressed completely or improved
Marzo-Ortega, et al.
Mean hip and spine BMD increased with 24 weeks’ etanercept treatment
Gorman, et al.
80% etanercept-treated patients, 30% placebo-treated patients achieved ASAS 20 at 4 months
6-month extension: 83%, 80%, 60% achieved ASAS 20, ASAS 50, ASAS 70, respectively
95% of patients treated only with etanercept (not placebo) over 10 months achieved ASAS 20

Слайд 24

Etanercept for the Treatment of AS: Clinical Trials (cont)
Brandt, et al.
57%

etanercept-treated patients and 6% placebo-treated patients improved at least 50% on BASDAI
56% in placebo group improved following switch to etanercept
Improvements ceased once etanercept therapy was discontinued
Davis, et al.
57% etanercept-treated patients and 22% placebo-treated patients achieved ASAS 20 at 24 weeks

Слайд 25

Etanercept: Adverse Events
*P<.0001; †P<.050; ‡P<.020

Слайд 26

Etanercept: Adverse Events (cont)
Serious infections and sepsis
Mainly in patients with underlying

illness or receiving immunosuppressive therapy
CNS demyelinating disorders
Causal relationship unclear
Use with caution or avoid use in patients with transverse myelitis, optic neuritis, multiple sclerosis
Pancytopenia
Causal relationship unclear
Use with caution in patients with history of hematologic abnormalities
Autoantibody formation
– Discontinue if lupus-like symptoms are observed
Heart failure
Carefully monitor if prescribed to patients with heart failure

Слайд 27

Infliximab for the Treatment of AS: Clinical Trials
Brandt, et al.
≥ 50%

improvement on outcome variables (ie, BASDAI, BASFI, pain on VAS, BASMI, QOL (SF-36) with 5 mg/kg dose of infliximab; ≥ 15% improvement with 3 mg/kg dose
Braun
53% of infliximab-treated patients and 9% placebo-treated patients experienced regression of disease activity of ≥ 50%
Function and quality of life significantly improved with infliximab treatment (P<.0001)
Van den Bosch
Significant improvement with infliximab compared with placebo on patient and physician global assessments of disease activity (P<.001)

Слайд 28

Infliximab for the Treatment of AS: Clinical Trials (cont)
Stone, et al.
Improvement

of > 60% at week 6 and > 75% at week 14 observed in BASDAI, BASFI, patient global assessment, physician global assessment, spinal pain and total body pain, and HAQ
Improvement on MRI scans
Maksymowych, et al.
Significant improvement* on BASDAI; significant mean reduction in BASFI, BASGI, ESR, and CRP at week 14
Efficacy sustained at 1 year

*P<.001, all parameters except CRP, P=.01

Слайд 29

Infliximab: Adverse Events
* Approximation based on all clinical studies

Слайд 30

Infliximab: Adverse Events (cont)
Serious infections and sepsis
Cases in patients on concomitant

immunosuppressive therapy
Neurologic events
Use with caution in patients with pre-existing CNS demyelinating or seizure disorders
Autoantibody formation
Discontinue if lupus-like symptoms are observed
Heart failure
Consider other treatment options in patients with heart failure
Closely monitor patients if infliximab is administered

Слайд 31

Anti-TNF Agents: Summary
Anti-TNF agents target underlying inflammatory process
Alter disease progression
Provide symptomatic

relief
Recommended treatment after trial of chronic daily NSAIDs, physical therapy, and regular exercise
Good safety and tolerability profiles
Long-term data needed
Implement treatment guidelines to ensure proper treatment given to appropriate patients
Treatment algorithm presented on next two slides

Слайд 32

AS Treatment Algorithm: Patients with Axial AS
Alternative Options
Pamidronate
Thalidomide
*Only biologic approved for treatment

of AS in US and Europe
†Approved in Europe only for treatment of AS
This treatment algorithm contains unlabeled use of infliximab, pamidronate and thalidomide.

Anti-TNF agents
Etanercept 50 mg SC per week as two 25 mg injections in the same day or 3-4 days apart*
Infliximab 5 mg/kg at 0, 2, and 6 weeks and every 6 to 8 weeks thereafter†
Contraindicated in patients with infections, tuberculosis, multiple sclerosis, lupus, malignancy, and pregnancy/lactation

Initiate physical therapy plan with long-
term exercise program to accompany
pharmacologic intervention
Emphasize posture, range of motion, and strengthening

NSAIDs or Selective COX-2 inhibitors
Efficacy and safety comparable between non-selective agents
Selective COX-2 efficacy comparable, better safety profile, higher cost that non-selective NSAIDs
Failure of at least two different NSAIDs/selective COX-2 inhibitors
for minimum of 3 months

Guidelines in Rheumatology

Содержание

Genetic Predisposition for Development of Ankylosing Spondylitis (AS)AS and HLA-B27 –

Natural History of ASHighly variableEarly stages: spontaneous remissions and exacerbationsSpectrum of

Burden of IllnessFunctional disabilityPotential complicationsQuality-of-life issuesPain, stiffness, fatigue, sleep problemsHealthcare costs

Obstacles to Desirable Outcomes in AS Until RecentlyDiagnostic and classification limitationsLack

Advances in Medicine: Hope for Patients With ASIncreased understanding of pathophysiologic processes

Pathogenesis of ASIncompletely understood, but knowledge increasingInteraction between HLA-B27 and T-cell

Clinical Features of AS

Modified New York Criteria for the Diagnosis of ASClinical CriteriaLow back

Disease Activity AssessmentBASFI = Bath Ankylosing Spondylitis Functional IndexBASDAI = Bath

Bath Ankylosing Spondylitis Functional Index (BASFI)Visual analog scale (VAS) – 10

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)A self-administered instrument (using 10-cm

ASsessment in Ankylosing Spondylitis (ASAS)ASAS 20: An improvement of > 20%

Introduction of Anti-TNF Agents for the Treatment of Ankylosing SpondylitisUS Modifications

Tumor Necrosis Factor: Functions of the Proinflammatory CytokineStimulation of endothelial cells

Pathogenesis of Joint Destruction Bone ErosionsMacrophagesEndotheliumSynoviocytes↑ Proinflammatory cytokines↑ Chemokines↑ Adhesion molecules↑

US Modifications of the ASAS International Guidelines: Appropriate Patients for Anti-TNF

Contraindications for Anti-TNF TherapyCurrent or recurrent infectionsTuberculosisMultiple sclerosisLupus MalignancyPregnant or lactating

Monitoring and Discontinuing Treatment With Anti-TNF AgentsASAS core set of outcome

Anti-TNF AgentsEtanerceptApproved in the United States and Europe for treatment of