Guidelines in Rheumatology презентация

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

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

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

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

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

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

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

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

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

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?

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)

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

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

Metalloproteinase synthesis

Articular Cartilage
Degradation

Increased Cell Infiltration

Increased
Inflammation

Osteoclast
progenitors

↑ RANKL expression

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

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

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

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

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

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

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

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)

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

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

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

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

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

DMARDs
Preferably sulfasalazine

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