1. EULAR recommendations for the management of psoriatic arthritis: 2015 update

2. Objective Target population: patients with psoriatic arthritis (PsA)
Objective: to update the 2011 EULAR management recommendations for PsA
Dealing with general treatment principles
And pharmacological non topical treatment
Musculoskeletal manifestations: rheumatologists‘ point of view
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

3. Methods
Meeting of steering group (June 2014): decisions on scope of the literature review
Systematic literature review of drugs
General literature review of treatment strategies, prognosis and comorbidities
Taskforce full meeting (January 2015):
Presentation of literature review
Discussions based on the 2010 recommendations
Elaboration of updated recommendations
Determination of level of strength and grade of recommendations
Votes by on level of agreement of Taskforce members (0-10 where 10 is full agreement)
Oxford levels of evidence, 2009

4. Systematic literature review
Systematic literature review of drugs (2010-Dec. 2014, Sofia Ramiro):
NSAIDs, glucocorticoids, csDMARDs, bDMARDs including novel modes of action and biosimilars, tsDMARDs
Randomised controlled trials
Efficacy on all manifestations of PsA, safety
N articles or abstracts analysed:
NSAIDs, glucocorticoids
TNFinhibitors 19
Strategy trial 1
bDMARDs targeting IL12/23 4
csDMARDs 3
bDMARDs targeting IL17 5
biosimilars
PDE4-inhibitor 10
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

5. Five overarching principles
EULAR recommendations for the management of psoriatic arthritis: 2015 update
Five overarching principles
Psoriatic arthritis is a heterogeneous and potentially severe disease, which may require multidisciplinary management.
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.
Rheumatologists 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.
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

6. Recommendations Recommendation 1
EULAR recommendations for the management of psoriatic arthritis: 2015 update
Recommendations
Recommendation 1
Treatment should be aimed at reaching the target of remission or, alternatively, LDA or MDA, by regular monitoring and appropriate adjustment of therapy 2
In patients with PsA, NSAIDs may be used to relieve musculoskeletal signs and symptoms 3
In 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 dose 5
In patients with peripheral arthritis and an inadequate response to at least one csDMARD, therapy with a bDMARD, usually a TNF inhibitor, should be commenced
LDA: Low disease activity; MDA: minimal disease activity; EAM: extra-articular manifestation
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

7. Recommendations Recommendation 6
EULAR recommendations for the management of psoriatic arthritis: 2015 update
Recommendations
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 considered 7
In 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 considered 8
In 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 inhibitor 9
In 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 inhibitor 10
In patients who fail to respond adequately to a bDMARD, switching to another bDMARD should be considered, including switching between TNF inhibitors
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

8. EULAR 2015 RECOMMENDATIONS FOR THE MANAGEMENT OF PSORIATIC ARTHRITIS*
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
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**
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
(with or without major skin involvement)
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*

9. Switch to another TNF-inhibitor or another mode of action
Phase IV
Lack of
efficacy and/or
toxicity in phase lII
Change treatment
Switch to another TNF-inhibitor
or another mode of action
or a tsDMARD
(± csDMARD)
Achieve target***
within 3-6 months No
Yes
Continue
* 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.

10. Algorithm for the Management of PsA
EULAR recommendations for the management of psoriatic arthritis: 2015 update
Algorithm for the Management of PsA
Phase 3
Phase 1
Arthritis with adverse prognostic factors**
Arthritis without adverse prognostic factors**
Clinical diagnosis of active** psoriatic arthritis
Lack of efficacy and/or toxicity in Phase 2
Adverse prognostic factors**
Major skin involvement
(with or without major skin involvement)
(also in Phases 2–4)
Start nonsteroid anti-inflammatory drugs ± local glucocorticoid injections
Predominant axial disease or enthesitis
Go directly to Phase 2
Consider consulting a dermatologist
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)
Active target*** within 3–6 months No
Failure Phase 1: go to Phase 2
Active target*** within 3–6 months No
Yes
Continue
Failure Phase 3: go to Phase 4
Active target*** within 3–6 months No
Yes
Continue
Phase 2
Phase 4
Lack of efficacy and/or toxicity in Phase 3
Lack of efficacy and/or toxicity in Phase 1 (or adverse prognostic factors)
Predominantly axial disease or severe enthesitis
Contraindication for methotrexate
Change treatment: switch to second TNF inhibitor or another mode of action or a tsDMARD (±csDMARD)
Start leflunomide or sulfasalazine (or cyclosporine A)
Start methotrexate (consider appropriate close)
Go directly to Phase 3
Failure Phase 2: go to Phase 3
Active target*** within 3–6 months No
Yes
Continue
Active target*** within 3–6 months No
Yes
Continue
* 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.
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

11. Summary Table Oxford Level of Evidence
Recommendation number
Level of evidence
Grade of recommendation
Level of agreement (mean± standard deviation, 0-10) 1. 1b A
9.6±0.9 2.
9.6±0.8 3.
1b/3 B
9.4±0.8 4.
3b/4 C
9.1±1.2 5.
9.5±0.7 6.
9.1±1.1 7.
8.5±1.4 8. 9.
9.6±0.6
10.
9.6±0.7
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

12. Lay version of recommendations
EULAR recommendations for the management of psoriatic arthritis: 2015 update
Lay version of recommendations
Recommendation 1
Treatment 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. 2
Non-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. 3
csDMARDs 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. 4
Steroid 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.
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

13. Lay version of recommendations
EULAR recommendations for the management of psoriatic arthritis: 2015 update
Lay version of recommendations
Recommendation 5
bDMARDs 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. 6
If 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.
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

14. Lay version of recommendations
EULAR recommendations for the management of psoriatic arthritis: 2015 update
Lay version of recommendations
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. 9
bDMARDs 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. 10
People 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
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

15. Conclusions
Update of the EULAR recommendations for the management of PsA
5 overarching principles regarding treatment objectives and treatment strategy in PsA
10 practical recommendations regarding pharmacological non-topical treatment
New drugs will allow rotations of drugs across different mechanisms of action, ultimately benefiting patients with PsA.
New drugs placed in the algorithm
Decisions taken reflect a balance of efficacy and long-term safety data with costs
More long-term data needed on the new drugs

16. Acknowledgements: PsA update Taskforce
Convenor: J. Smolen
Epidemiologist: L. Gossec
Fellow: S. Ramiro
Steering 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. Zink
Gossec L, Smolen JS et al. Ann Rheum Dis 2016;75:499–510

17. DISCLOSURES
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, UCB
The development of these recommendations was funded by EULAR. No company representative was present at any time during the process.