DMARDs in Management of Axial Ankylosing Spondylitis

Dr. Homayra Tahseen Hossain

Assistant Professor , Medicine Popular Medical College Hospital

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Introduction

• Ankylosing spondylitis (AS, from Greek ankylos, crooked; spondylos, vertebra; -itis, inflammation),

• is a chronic inflammatory disease of the axial skeleton, with variable involvement of peripheral joints and nonarticular structures.

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• AS is one of the sero -ve spondyloarthropathies.

• It has strong genetic predisposition , > 90 % HLA B27 positive.

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• Prevalence- 0.2-0.9% • Age of onset- onset usually peaks in 2nd &

3rd decades of life. • Gender- occurs more frequently in male (male: female- 3:1)

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• The diagnosis of AS requires fulfilment of the modified New York criteria.

• It requires at least 1 clinical manifestation and at least 1 radiographic parameter.

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• Clinical manifestations include ≥ 3 months of inflammatory back pain that

improves with exercise and exacerbated by rest, limitation of lumbar motion in both frontal

and sagittal planes, and limitation of chest expansion compared to the

normative population.

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• Radiographic parameters include ≥ grade 2 sacroiliitis bilaterally or grade 3 or 4 sacroiliitis unilaterally.

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• AS is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary treatment coordinated by the rheumatologist.

• There is no cure for AS, although treatments and medications can reduce symptoms & pain.

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• To relieve pain, stiffness and fatigue and • to prevent structural

damage

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Treatment of As

Non-pharmacological

Education & Exercise

Pharmacological

NSAIDs

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Surgery: In severe cases of AS (joint replacement)

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• Conventional synthetic DMARD (csDMARD) therapy in patients with axial spondyloarthritis (SpA) is a matter of continuous debate.

• Traditional DMARDs like Sulfasalazine or Methotrexate can be used in peripheral arthritis, but there is NO evidence for their efficacy for the treatment of axial AS.

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However, newer biologic DMARDs TNF α blockers( Adalimumab, Certolizumab, Etanercept, Golimumab & Infliximab) have definite proven role in axial AS.

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• British Society of Rheumatology (BSR) guidelines-‘Biologics for the treatment of axial spondyloarthritis(including AS) ‘ -Updated on August’ 2015

• The evidence for these guidelines is based on a systematic literature search of Medline,

EMBASE and the Cochrane library up to 30th June 2014.

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18 eligible RCTs were identified which evaluated the efficacy of the 5 currently available TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab and infliximab) in patients with AS.

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10 of the 16 placebo-controlled RCTs, all the used the ASAS20 response rates as primary efficacy outcome, with the time scale varying between 12-24 weeks.

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• Improvement in any 3 modalities by 20% or more without deterioration in the 4th modality-

1. Pain 2. Inflammation 3. Well-being 4. Function

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All of the placebo-controlled trials achieved the primary efficacy end-point.

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No other biologic agents have demonstrated efficacy in AS or are licensed for this indication, so cannot be recommended for the treatment of AS.

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• Evidence for anti-TNF therapy on radiographic disease progression (new bone formation and ankylosis) is currently limited. • Large, controlled, longer term clinical trials are

needed to clarify whether these drugs may be disease modifiers.

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Treatment guideline

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Whom to treat?

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1. The patient’s disease satisfies the modified New York criteria.

2. AS is active. Active disease is defined by a BASDAI and

spinal pain VAS ≥ 4 despite standard therapy. BASDAI should be measured on 2 occasions at

least 4 weeks apart (to avoid overtreatment of patients with a short-lived flare of disease)

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Standard therapy is defined as 2 NSAIDs at maximal tolerated dose for at least 2 weeks each unless contraindicated.

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1. Women who are pregnant or breast-feeding. 2. Active significant infection. 3. Septic arthritis of a native joint within the last 12

months. 4. Sepsis of a prosthetic joint within the last 12

months or indefinitely if the joint remains in situ.

5. New York Heart Association (NYHA) grade 3 or 4 CCF for infliximab.

6. Clear history of demyelinating disease.

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Which Anti TNF drug to choose?

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In the absence of head-to-head comparisons, systematic reviews have shown no statistical difference in efficacy between infliximab, golimumab, etanercept, or adalimumab in the treatment of AS.

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Choice of drug should be a mutual decision between patient and clinician, taking into account factors such as- • Route, • frequency of administration, and • the presence of co-morbidities.

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How to assess response?

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Initial efficacy response should be assessed following 3 to 6 months of therapy and responders should then be reassessed every 6 months.

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Response is defined as reduction of BASDAI and spinal pain VAS by 2 or more units from baseline.

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When to withdraw treatment?

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• Development of severe adverse effects (as for rheumatoid arthritis).

• In the absence of an initial clinical response by 6 months, or failure to maintain response at 2

consecutive assessments at least 4 weeks apart, withdrawal of that anti-TNF agent should be considered.

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• There is no evidence to support the

withdrawal of anti-TNF therapy in treatment responders.

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In the event of anti-TNF failure due to inefficacy or adverse event, an alternative anti-TNF agent should be offered if clinically appropriate.

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Treatment algorithm for biologic therapy in axial AS

Meets modified New York criteria or has Bone Marrow Oedema in sacroiliac joints on MRI ?

BASDAI and spinal VAS ≥ 4 despite standard therapy

Consider trial of biologics

Assess efficacy after 3-6 months

Consider swithching to another biologic drug in event of side effects or inefficacy

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The safety of anti-TNF therapies in axial AS is comparable to other inflammatory joint diseases such as RA. There is little evidence to suggest that safety issues differ hugely with different disease groups

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• High cost, • Parenteral route of administration • Side effects due to immunosuppression

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• Whether DMARDs are effective in axial AS is a

debatable issue.

• Traditional DMARDs like Sulfasalazine or Methotrexate can be used in peripheral arthritis, but there is NO evidence for their efficacy for the treatment of axial AS.

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• Newer biologic DMARDs TNF α blockers have definite proven role in axial AS.

• According to BSR guidelines- ‘biologics for the treatment of axial spondyloarthritis (including AS): Anti TNF therapy is effective at reducing disease activity and spinal pain in axial AS.

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• High cost, parenteral route of administration & side effects due to immunosuppression are the main limitations of using these agents.

• So it is the responsibility of the clinician to

assess risk benefit ratio before starting treatment with anti-TNF therapy for axial AS.

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