EULAR recommendations - PowerPoint Presentation

Slide1

EULAR

recommendations

for

the

management

of

psoriatic

arthritis

: 2015 updateSlide2

Objective

Target

population: patients with psoriatic arthritis (PsA)Objective: to update the 2011 EULAR management recommendations for PsADealing with general treatment principlesAnd pharmacological non topical treatmentMusculoskeletal manifestations: rheumatologists‘ point of view

Gossec L,

Smolen

JS et al.

Ann

Rheum

Dis

2016;75:499–510Slide3

Methods

3

Meeting of steering group (June 2014): decisions on scope of the literature reviewSystematic literature review of drugsGeneral literature review of treatment strategies,

prognosis

and

comorbiditiesTaskforce full meeting (January 2015): Presentation of literature reviewDiscussions based on the 2010 recommendationsElaboration of updated recommendationsDetermination of level of strength and grade of recommendationsVotes by email on level of agreement of Taskforce members(0-10 where 10 is full agreement)

O

xford

levels

of

evidence

, 2009Slide4

Systematic literature review

Systematic

literature review of drugs (2010-Dec. 2014, Sofia Ramiro):NSAIDs, glucocorticoids, csDMARDs, bDMARDs including novel modes of action and biosimilars, tsDMARDsRandomised controlled trialsEfficacy on all

manifestations

of

PsA, safetyN articles or abstracts analysed:NSAIDs, glucocorticoids0TNFinhibitors19

Strategy trial

1

bDMARDs targeting IL12/23

4csDMARDs3bDMARDs targeting IL175biosimilars0PDE4-inhibitor10

Gossec L,

Smolen

JS et al.

Ann

Rheum

Dis

2016;75:499–510Slide5

Psoriatic arthritis is a heterogeneous and potentially severe disease, which may require multidisciplinary management.

Five overarching principles

Treatment of psoriatic arthritis patients should aim at the best care and must be based on a shared decision between the patient and the rheumatologist, considering efficacy, safety and costs.

Gossec L,

Smolen

JS et al.

Ann Rheum Dis 2016;75:499–510Rheumatologists are the specialists who should primarily care for the musculoskeletal manifestations of patients with psoriatic arthritis; in the presence of clinically significant skin involvement a rheumatologist and a dermatologist should collaborate in diagnosis and management.

The primary goal of treating patients with psoriatic arthritis is to maximise health-related quality of life, through control of symptoms, prevention of structural damage, normalisation of function and social participation; abrogation of inflammation is an important component to achieve these goals.

When managing patients with psoriatic arthritis, extra-articular manifestations, metabolic syndrome, cardiovascular disease and other co-morbidities should be taken into account.

EULAR recommendations for the management of psoriatic arthritis: 2015 updateSlide6

Recommendations

Recommendation

1Treatment should be aimed at reaching the target of remission or, alternatively, LDA or MDA, by regular monitoring and appropriate adjustment of therapy 2In patients with PsA, NSAIDs may be used to relieve musculoskeletal signs and symptoms3In patients with peripheral arthritis, particularly those with many swollen joints, structural damage, high ESR/CRP and/or clinically relevant EAMs, csDMARDs should be considered, with MTX preferred in those with relevant skin involvement

4

Local injections of glucocorticoids should be considered as adjunctive therapy in

PsA

; systemic glucocorticoids may be used with caution at the lowest effective dose5In patients with peripheral arthritis and an inadequate response to at least one csDMARD, therapy with a bDMARD, usually a TNF inhibitor, should be commencedLDA: Low disease activity; MDA: minimal disease activity; EAM: extra-articular manifestationEULAR recommendations for the management of psoriatic arthritis: 2015 updateGossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510Slide7

Recommendation

6

In patients with peripheral arthritis and an inadequate response to ≥1 csDMARD, in whom TNF inhibitors are not appropriate, bDMARDs targeting IL12/23 or IL17 pathways may be considered7In patients with peripheral arthritis and an inadequate response to at least one csDMARD, in whom bDMARDs are not appropriate, a targeted synthetic DMARD such as a PDE4-inhibitor may be considered8In patients with active enthesitis and/or

dactylitis

and insufficient response to NSAIDs or local glucocorticoid injections, therapy with a

bDMARD

should be considered, which according to current practice is a TNF inhibitor9In patients with predominantly axial disease that is active and has insufficient response to NSAIDs, therapy with a bDMARD should be considered, which according to current practice is a TNF inhibitor10In patients who fail to respond adequately to a bDMARD, switching to another bDMARD should be considered, including switching between TNF inhibitorsEULAR recommendations for the management of psoriatic arthritis: 2015 updateGossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

RecommendationsSlide8

Phase I

Phase III

Phase IV

Adverse

prognostic

factors

**

Major

skin

involvement

(also in

phase

II-IV)

Clinical diagnosis

of

active**

psoriatic

arthritis

Achieve target***

within 3-6 months

Go directly to

phase II

Consider consulting

a dermatologist

Failure phase I:

go to phase II

No

Yes

Continue

Lack of efficacy and/or

toxicity in phase

lI

Achieve target***

within 3-6 months

No

No

Yes

Continue

Achieve target***

within 3-6 months

Failure phase III:

go to phase IV

Start a biological agent –

usually a TNF-inhibitor, but

If this is contraindicated, an IL-12/23- or IL-17-inhibitor

§

may be used, in special cases

§§

also a

tsDMARD

(

±

csDMARD

)

Arthritis

without

adverse

prognostic

factors

**

Yes

Continue

No

Achieve target***

within 3-6 months

Lack of

efficacy and/or

toxicity in phase lII

Start a second

synthetic DMARD:

Leflunomide,

Sulfasalazine,

MTX, or Cyclosporine A

(or combination therapy)

Change treatment

Switch to another TNF-inhibitor

or another mode of action

or a tsDMARD

(

±

csDMARD) (9)

Phase II

Contraindication

for

methotrexate

Predominantly axial disease or

severe

enthesitis

Lack of efficacy and/or toxicity in phase I

(or adverse prognostic factors)

Go directly to phase III

Start methotrexate

(consider appropriate dose)

Failure phase II:

go to phase III

No

Yes

Continue

(with or without major skin involvement)

Achieve target***

within 3-6 months

Start non-steroidal

antiinflammatory

drugs

± local glucocorticoid

injections

Start leflunomide

or sulfasalazine

(or cyclosporine A)

Arthritis with adverse

Prognostic

factors

**

Predominant axial

disease or enthesitis

* Because of the variable nature of the disease, not all situations can be covered by this figure; therefore it is important to consult the

full text; dotted lines refer to situations where deleting a phase is recommended.

** Active disease: 1 or more tender and inflamed joint and/or tender enthesis point, and/or dactylitic digit, and/or inflammatory back pain; adverse prognostic factors:

>

5 active joints; or high functional impairment due to activity; or damage; or past glucocorticoid use.

***The treatment target is clinical remission or, if remission is unlikely to be achievable, at least low disease activity; clinical remission is the absence of signs and symptoms.

EULAR 2015 RECOMMENDATIONS FOR THE

MANAGEMENT OF PSORIATIC ARTHRITIS*Slide9

Phase IV

Yes

Continue

No

Achieve target***

within 3-6 months

Lack of

efficacy and/or

toxicity in phase lII

Switch to another TNF-inhibitor

or another mode of action

or a

tsDMARD

(

±

csDMARD

)

* Because of the variable nature of the disease, not all situations can be covered by this figure; therefore it is important to consult the

full text; dotted lines refer to situations where deleting a phase is recommended.

** Active disease: 1 or more tender and inflamed joints; tender enthesis point, dactylitic digit, and/or inflammatory back pain; adverse prognostic factors:

>

5 active joints; radiographic damage; elevated acute phase reactants; extraarticular manifestations, especially dactylitis.

***The treatment target is clinical remission or, if remission is unlikely to be achievable, at least low disease activity; clinical remission is the absence of signs and symptoms.

§

For patients with peripheral arthritis and an inadequate response to at least one csDMARD, in whom TNF inhibitors are not appropriate. With

predominant spinal involvement, active enthesitis and/or dactylitis no csDMARD needed - use a bDMARD with preference for a TNFi.

§§

For peripheral arthritis and an inadequate response to at least one csDMARD, in whom bDMARDs are not appropriate.

Change treatmentSlide10

Arthritis without

adverse prognostic factors**

Arthritis with adverse prognostic factors**Algorithm for the Management of PsA* Because of the variable nature of the disease, not all situations can be covered by this figure.** Active disease, ≥1 tender and inflamed joint; tender enthesis point and/or dactylitic digit and/or inflammatory back pain; adverse prognostic factors, ≥5 active joints; radiographic damage; elevated acute phase reactants; extraarticular manifestations, especially dactylitis. ***Treatment target is clinical remission or at least low disease activity.† For patients with peripheral arthritis and inadequate response to ≥1 csDMARD, in whom TNF inhibitors are not appropriate. With predominant spinal involvement, active

enthesitis

, and/or

dactylitis

, no csDMARD needed—use a bDMARD with preference for a TNFi. csDMARD=conventional synthetic DMARD; DMARD=disease-modifying antirheumatic drug; IL=interleukin; MTX=methotrexate; TNF=tumor necrosis factor; tsDMARD=targeted synthetic DMARD.Phase 1Clinical diagnosis of active** psoriatic arthritisStart nonsteroid anti-inflammatory drugs ± local glucocorticoid injectionsActive target***within 3–6 monthsLack of efficacy and/or toxicity in Phase 1 (or adverse prognostic factors)Start methotrexate(consider appropriate close)Go directly toPhase 2Consider consulting a dermatologist

Failure Phase 1:

go to Phase 2

Start leflunomide or sulfasalazine

(or cyclosporine A)Go directly toPhase 3Phase 2NoYesContinueActive target***within 3–6 monthsFailure Phase 2: go to Phase 3NoYesContinuePhase 3Lack of efficacy and/or toxicity in Phase 2Predominant axial disease or enthesitisActive target***within 3–6 monthsActive target***within 3–6 monthsLack of efficacy and/or toxicity in Phase 3Change treatment:switch to second TNF inhibitor or another mode of action or a tsDMARD (±csDMARD)NoFailure Phase 3:go to Phase 4NoYes

Continue

Phase 4

Active target***

within 3–6 months

No

Yes

Continue

Start a biological agent usually TNF-inhibitor, but if this is contraindicated, IL- 12/23 or IL-17 inhibitors

†

may be used, in special cases also a

tsDMARD

(±

csDMARD

)

Start a second

csDMARD

: Leflunomide, sulfasalazine, MTX, or cyclosporine A

(or combination therapy)

Adverse prognostic factors**

Major skin involvement

(with or without major skin involvement)

(also in

Phases 2–4)

Contraindication for methotrexate

Predominantly axial disease or severe

enthesitis

EULAR recommendations for the management of psoriatic arthritis: 2015 update

Gossec L,

Smolen

JS et al.

Ann

Rheum

Dis

2016;75:499–510Slide11

Summary

Table Oxford Level of Evidence

11Recommendation numberLevel of evidenceGrade of recommendationLevel of agreement (mean± standard deviation, 0-10) 1.1bA9.6±0.92.1bA

9.6±0.8

3.

1b/3

B 9.4±0.84.3b/4C9.1±1.25.1b B9.5±0.76.1bB9.1±1.17.1bB8.5±1.48.1bB9.1±1.2

9.

1b

B

9.6±0.610.1bB9.6±0.7Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510Slide12

Lay version of recommendations

Recommendation

1Treatment should aim for remission or low disease activity; regular monitoring and adjustment of therapy will help achieve this goal.The goal of your treatment should be remission or low disease activity. Remission means that the disease is well-controlled, there is no longer any inflammation such as swollen joints and no signs of inflammation in blood tests. However, there may still be some symptoms even in remission. Low disease activity means that your levels of inflammation are minimal. Your doctor can help you to achieve these goals by keeping a close eye on your disease by examining you and asking for tests as needed. Your doctor may also adjust your treatment up or down as needed. 2Non-steroidal anti-inflammatory drugs may be used.NSAIDs can be used to relieve signs and symptoms in your joints and muscles. They can help to reduce pain and improve mobility (movement) in your joints, but do not inhibit progression of joint damage. These drugs will not preserve long-term functioning and will not help the skin. 3csDMARDs

should be used at an early stage in people with arthritis in the joints of their arms, hands, legs or feet or other symptoms.

Some people may have arthritis either in the large joints such as elbows, knees and wrists or in the small joints of their hands and feet (this is called peripheral arthritis). In these people,

csDMARDs

should be considered at an early stage, especially if they have many swollen joints, or symptoms in other parts of their body, such as their eyes. Methotrexate is the preferred drug, especially if you also have skin lesions as part of your disease. 4Steroid injections should be considered, and systemic steroids may be used with caution at the lowest effective dose.Local injections of glucocorticoids (steroids) for example in joints or near tendons can be used in people with psoriatic

arthritis

to

provide relief. Steroids taken by other means (e.g. as tablets) are not usually recommended but may be used with caution at the lowest possible dose. EULAR recommendations for the management of psoriatic arthritis: 2015 updateGossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510Slide13

Lay version of recommendations

Recommendation

5bDMARDs should be used in people with peripheral arthritis who have not responded to at least one csDMARD

.

If

you

have peripheral arthritis and have not have good effects from treatment with at least one csDMARD for several months, you may benefit from therapy with a bDMARD. This will usually be a TNF inhibitor since these are the bDMARDs we have the most

experience

with. These work by blocking a molecule called TNF (which stands for tumour necrosis factor). TNF is involved in inflammation. 6If TNF inhibitors are not appropriate, bDMARDs targeting different cells or molecules may be considered for peripheral arthritis.If you have peripheral arthritis and are unable to take TNF inhibitors for some reason, a bDMARD that targets a different cell or molecule may be considered. Some drugs have recently come on the market and seem to work as well

as TNF

inhibitors

.

7

tsDMARDs

may be used for peripheral arthritis if

bDMARDs

are not appropriate.***

If you have peripheral arthritis and are unable to take

bDMARDs

for any reason, a

tsDMARD

may be considered. These types of medicine work in a different way to

bDMARDs

and are given as pills rather than injections or infusions.

EULAR recommendations for the management of psoriatic arthritis: 2015 update

Gossec L,

Smolen

JS et al.

Ann

Rheum

Dis

2016;75:499–510Slide14

Recommendation

8

bDMARDs should be considered for people with inflamed tendons, ligaments, and sausage-like fingers or toes.***If you have

inflamed

tendons or ligaments or

inflamed

fingers or toes (sometimes called sausage-like), and have not had good effects from NSAIDs or steroids injections, a bDMARD should be considered even if you have not been given a csDMARD. 9bDMARDs should be considered for people with axial

disease

.***

If

your disease is mostly in your back (axial disease) and has not got better with NSAIDs, a TNF inhibitor should be considered without first prescribing a csDMARD.10People who do not respond to bDMARDs should switch treatment.If your disease does not improve with a bDMARD, you should be switched to another kind. This might mean switching to another brand of TNF inhibitor, or to a different type of bDMARD that works on a different pathway, or in some cases to a

tsDMARD

EULAR recommendations for the management of psoriatic arthritis: 2015 update

Gossec L,

Smolen

JS et al.

Ann

Rheum

Dis

2016;75:499–510

Lay version of recommendationsSlide15

Conclusions

Update of the EULAR

recommendations for the management of PsA5 overarching principles regarding treatment objectives and treatment strategy in PsA10 practical recommendations regarding pharmacological non-topical treatment

New drugs

will

allow rotations of drugs across different mechanisms of action, ultimately benefiting patients with PsA.Slide16

Convenor

:

J. Smolen Epidemiologist: L. Gossec Fellow: S. RamiroSteering group: M. Cutolo, M. de Wit, M Dougados, P. Emery, R. Landewé, S. Oliver, D. van der Heijde Other patient partners: M. Maccarone, N. Betteridge Other

health

professional:

E.

Haglund Other physicians: D. Aletaha, J. Braun, G. Burmester, J. D. Cañete, N Damjanov, O. FitzGerald, P. Helliwell, T.K. Kvien, R Lories, T. Luger (dermatologist), H. Marzo-Ortega, D. McGonagle, I. B. McInnes, I Olivieri, K Pavelka, G. Schett, J. Sieper, F. van den Bosch, D Veale, J Wollenhaupt, A. ZinkAcknowledgements:PsA update Taskforce

Gossec L,

Smolen

JS et al.

Ann Rheum Dis 2016;75:499–510Slide17

Many authors of these recommendations have received honoraria for talks and/or advisory board participation and/or research grants from, and/or were investigators of clinical trials performed by one or more pharmaceutical companies.

These comprise:

Abbvie, Amgen, Astra-Zeneca, BMS, Celgene, Celltrion, Glaxo, Janssen, Lilly, Medimmune, Merck-Serono, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, UCBThe development of these recommendations was funded by EULAR. No company representative was present at any time during the process.

DISCLOSURES