Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.

com

Recommendation

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies
L Gossec,1,2 J S Smolen,3,4 C Gaujoux-Viala,5,6 Z Ash,7,8 H Marzo-Ortega,7,8 D van der Heijde,9 O FitzGerald,10 D Aletaha,3 P Balint,11 D Boumpas,12 J Braun,13 F C Breedveld,9 G Burmester,14 J D Caete,15 M de Wit,16 H Dagnrud,17,18 K de Vlam,19 M Dougados,1,2 P Helliwell,7 A Kavanaugh,20 T K Kvien,17,18 R Landew,21 T Luger,22 M Maccarone,23 D McGonagle,7,8 N McHugh,24 I B McInnes,25 C Ritchlin,26 J Sieper,27 P P Tak,28 G Valesini,29 J Vencovsky,30 K L Winthrop,31 A Zink,32,33 P Emery,7,8
Additional supplementary data are published online only. To view these les please visit the journal online (http://ard. bmj.com/content/71/1.toc).

For numbered af liations see end of article Correspondence to Dr Laure Gossec, Service de Rhumatologie B, Hpital Cochin, 27, rue du Faubourg SaintJacques, 75014 Paris, France; laure.gossec@cch.aphp.fr LG and JSS contributed equally to the study (joint rst authors) Accepted 4 August 2011 Published Online First 27 September 2011

ABSTRACT Background Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). Methods The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. Results Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extraarticular manifestations of PsA. Five overarching principles and a research agenda were dened. Conclusion These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
The treatment of psoriatic arthritis (PsA) has changed dramatically over recent years, despite the lack of sufcient knowledge on aetiology and detailed pathogenesis. Observations that pro-inammatory cytokines may play important pathogenetic roles have led to the evaluation of novel therapies; indeed, new synthetic and biological disease-modifying antirheumatic drugs (DMARD) are widely used,15 with further treatment options anticipated in the near future.6 7 While psoriatic skin and joint disease have many facets in common, the pathways leading to their expression may differ, exemplied in the frequent distinct efcacy of various therapies on skin and joint disease

This paper is freely available online under the BMJ Journals unlocked scheme, see http:// ard.bmj.com/info/unlocked.dtl

(eg, phototherapy, fumaric acid or alefacept).812 PsA in itself is heterogeneous by virtue of its broad phenotypes of joint involvement (peripheral and spinal),13 but also its spectrum of extra-articular manifestations, whichaside from skin and nails comprise dactylitis and enthesopathy.14 15 The complexity of PsA and the relative paucity of randomised controlled clinical studies, let alone strategic trials, contrasts with the situation in rheumatoid arthritis (RA), another chronic and destructive inammatory joint disease. There are data on the usefulness of synthetic DMARD as well as the efcacy of biological DMARD, particularly tumour necrosis factor (TNF) inhibitors15 1618 in PsA, and there exist general recommendations for the use of biological agents.19 Recently, recommendations for PsA treatment were presented by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).20 21 These recommendations are comprehensive, with a special focus on skin disease, providing an initial treatment guidance set. However, clinicians can benet from concise, easy to follow guidance on the optimal use of available therapies and clear treatment strategies for PsA. Among other aspects, the efcacy of synthetic DMARD and the role of glucocorticoids remain under debate, and combination therapy of synthetic DMARD or synthetic DMARD with biological agents is relatively underresearched.17 22 Moreover, even disease activity assessment of PsA is under scrutiny, given that the measures used in clinical trials are mostly borrowed from RA23 with further methods under evaluation. Furthermore, therapeutic targets require denition.24 25 All of these reasons, as well as more recent insights, provided a rationale for the development of European League Against Rheumatism (EULAR) recommendations for the management of PsA. Rheumatologists require evidence-based guidance for the treatment of PsA with regard to synthetic and biological therapies, including the denition of treatment targets and assessment tools. To address the set task, EULAR convened a group of experts to produce evidence-based recommendations for the management of PsA with non-topical pharmacological therapies on the basis
Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation
of the EULAR standard operating procedures,26 and to develop a research agenda for future activities. requires NSAID treatment, as some patients may respond well to analgesics or may not feel in need of symptomatic therapy. We encourage the lowest dose and the shortest treatment duration possible with NSAID, in view of their potential toxicity. Data suggest that cyclooxygenase 2 inhibitors are as effective as nonselective NSAID in PsA.32 No data were found regarding the possible worsening of skin lesions following NSAID use.

METHODS
The task force aimed at aggregating available information on disease management in PsA into practical recommendations. The basis of its activities were the respective EULAR standardised procedures,26 which suggest the institution of an expert committee in charge of consensus nding, on the basis of evidence provided by a systematic literature review and expert opinion. The taskforce thus followed a similar path as other management recommendations, such as for RA, ankylosing spondylitis and osteoarthritis.2730 One of the aims of EULAR recommendations is to provide clear guidance that is easy to follow in clinical practice. The expert committee consisted of 28 rheumatologists, two patients, one infectious disease specialist, one dermatologist, one physiotherapist and two rheumatology fellows. The members of this task force came from 14 European countries and from the USA. This inclusive approach aimed at obtaining broad consensus and applicability of the recommendations. The process was both evidenced based and consensus based, as explained in supplementary text 1 (available online only), and included, between January 2010 and December 2010, two expert meetings, systematic literature reviews and extensive discussions. The literature search is published separately.31 A vote was obtained from the experts on the level of agreement with the nal recommendations. Votes for agreement or disagreement were performed anonymously, by giving a score from 0 (total disagreement) to 10 (total agreement) for each recommendation; the means and SD of scores from the whole group were calculated.

Treatment with synthetic DMARD

To date, there are few data on which to rest for the decision to start a synthetic DMARD. Who should be treated with DMARD? When to treat with DMARD? This should be addressed by future research. Based on the prognostic factors shown in the literature, the group considered that patients with active disease and potential poor prognosis should be started on DMARD. Active disease was dened globally as one or more tender and inamed joint and/or tender enthesis point and/or dactylitic digit and/or inammatory back pain; however, for the introduction of synthetic DMARD only joint involvement is taken into account. Poor prognosis refers here to the number of actively inamed joints (dened here as ve or more), elevated acute phase reactants, radiographic damage that is progressing, previous use of glucocorticoids, loss of function and diminished quality of life.31 37 Delay in the start of DMARD therapy may lead to worse outcomes, similar to RA,38 although data are scarce in this respect in PsA.20 39 Obviously, patients who have active disease despite previous NSAID therapy should receive a synthetic DMARD (this is stated as at an early stage in the recommendation; although the term early was not precisely dened, it is common to regard early as a few weeks to a maximum of 1 year). Regarding the choice of a DMARD, here again there are few data and almost no head-to-head comparisons. Based on the available literature, the experts recommended methotrexate as the rst-choice DMARD. This group decision was based in particular on broad therapeutic dose ranges, different application forms (by mouth, subcutaneous) and available data in PsA and in other inammatory diseases.3942 It is worth noting here that synthetic DMARD do not appear to be efcacious for treating enthesitis and axial disease (more details under recommendations 6 and 7, see table 1). When treating with methotrexate, careful consideration must be given to the prescription of an efcacious dose. While the most efcacious dose has not been determined for PsA and low doses may not be effective, it is evident in RA that doses in the order of 25 mg per week are more appropriate than lower doses.43 Other drugs to be considered include sulfasalazine, leunomide and ciclosporin A (although the use of this latter drug is limited by long-term toxicity issues).4 22 31 4446 The order presented here is not a ranking order. Clinical efcacy on joint involvement has also been published for gold salts and azathioprine, although for these drugs the level of evidence was low.31 None of the synthetic DMARD have been tested for (eg, ciclosporin, leunomide) and/or have demonstrated (eg, methotrexate, sulfasalazine, gold salts, azathioprin) structural efcacy in PsA.31 Although there is a lack of evidence on the efcacy of synthetic DMARD combinations, these may be considered.47 48 As a result of the potential for increased hepatic toxicity of methotrexate in PsA compared with other rheumatic conditions,49 50 transaminase enzymes should be carefully monitored in patients with PsA who receive treatment with methotrexate or leunomide, especially in cases of alcohol consumption, obesity, type II diabetes and non-alcoholic steatohepatitis or concurrent therapy with other potentially hepatotoxic drugs (eg, statins). In some patients, a liver biopsy has been recommended.51
5

RESULTS Overarching principles

Before addressing the actual treatment recommendations, the task force established principles deemed sufciently important to be conveyed to those affected by PsA or involved with the management of PsA. These principles regarding the care of patients with PsA are of such s generic nature that they were felt to be overarching. The complete wording and level of agreement are shown in table 1,and the explanatory text is in supplementary text 2 (available online only). The task force voted unanimously on these ve principles.

Recommendations
The process led to 10 recommendations on drug management and treatment strategies, presented in table 1 with levels of evidence and strengths of recommendations. The 10 recommendations are ordered by means of logical sequence or procedural and chronological hierarchy rather than by any major weight of importance. They also serve as the basis for the algorithm provided in gure 1.

NSAID for relief of signs and symptoms

The task force was unanimous in its view that in the vast majority of PsA patients, NSAID should be used as rst-line treatment, although the data regarding the usefulness of NSAID in PsA are limited.3133 NSAID have been shown to be efcacious on joint symptoms, although there is no demonstrated efcacy on skin lesions.31 Of course, cardiovascular and gastrointestinal risk3436 should be taken into account when prescribing NSAID, which explains the use of the word may in the wording of the recommendation. Furthermore, not everyone with signs and symptoms
Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation
Table 1 EULAR recommendations for the management of PsA, with levels of evidence, grade of recommendations and level of agreement
Overarching principles A. B. C. Psoriatic arthritis is a heterogeneous and potentially severe disease, which may require multidisciplinary treatment. 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. Rheumatologists are the specialists who should primarily care for the musculoskeletal manifestations of patients with psoriatic arthritis; in the presence of clinically signicant 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 longterm health-related quality of life, through control of symptoms, prevention of structural damage, normalisation of function and social participation; abrogation of inammation, targeted at remission, is an important component to achieve these goals. Patients should be regularly monitored and treatment should be adjusted appropriately. Grade of recommendation A B Level of agreement (meanSD) 9.80.5 9.80.8 9.60.8

D.

9.70.6

E.

9.70.7 Level of agreement (meanSD) 9.40.9 9.40.7

Recommendations 1. 2. In patients with psoriatic arthritis, non-steroidal anti-inammatory drugs may be used to relieve musculoskeletal signs and symptoms. In patients with active disease (particularly those with many swollen joints, structural damage in the presence of inammation, high ESR/CRP and/or clinically relevant extraarticular manifestations), treatment with disease-modifying drugs, such as methotrexate, sulfasalazine, leunomide, should be considered at an early stage. In patients with active psoriatic arthritis and clinically relevant psoriasis, a diseasemodifying drug that also improves psoriasis, such as methotrexate, should be preferred. Local injections of corticosteroids should be considered as adjunctive therapy in psoriatic arthritis; systemic steroids at the lowest effective dose may be used with caution. In patients with active arthritis and an inadequate response to at least one synthetic disease-modifying antirheumatic drug, such as methotrexate, therapy with a tumour necrosis factor inhibitor should be commenced. In patients with active enthesitis and/or dactylitis and insufcient response to nonsteroidal anti-inammatory drugs or local steroid injections, tumour necrosis factor inhibitors may be considered. In patients with predominantly axial disease that is active and has insufcient response to non-steroidal anti-inammatory drugs, tumour necrosis factor inhibitors should be considered. Tumour necrosis factor inhibitor therapy might exceptionally be considered for a very active patient naive of disease-modifying treatment (particularly those with many swollen joints, structural damage in the presence of inammation, and/ or clinically relevant extra-articular manifestations, especially extensive skin involvement). In patients who fail to respond adequately to one tumour necrosis factor inhibitor, switching to another tumour necrosis factor inhibitor agent should be considered. When adjusting therapy, factors apart from disease activity, such as comorbidities and safety issues, should be taken into account.

Level of evidence 1b *1b, 4

3.

1b

9.11.0

4.

3b, 4

8.91.2

5.

1b

8.91.5

6.

1b

8.51.5

7.

2b

9.30.9

8.

8.61.7

9. 10.

2b 4

B D

8.91.8 9.51.0

Recommendations with different levels of evidence within the recommendation are listed below. The level of agreement was computed as a 0 to 10 scale, based on 28 voters within the group. *In patients with active disease (particularly those with many swollen jointsusually 5, structural damage in the presence of inammation, high ESR/CRP and/or clinically relevant extra-articular manifestations), treatment with disease-modifying drugs, such as methotrexate, sulfasalazine, leunomide, should be considered; at an early stage. Local injections of corticosteroids should be considered as adjunctive therapy in psoriatic arthritis; systemic steroids at the lowest effective dose may be used with caution. CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; PsA, psoriatic arthritis.

Choice of synthetic DMARD in the presence of clinically relevant psoriasis

Some DMARD have shown efcacy in psoriasis. This is especially the case with methotrexate, but also ciclosporin A, leunomide and sulfasalazine.31 52 In patients with clinically relevant psoriasis, dened as psoriasis with impact on quality of life, these data should be taken into account for the choice of DMARD. In trials, the extent of psoriasis is measured through composite indices such as the PASI (Psoriasis Area and Severity Index). However, these recommendations are mainly aimed at rheumatologists, who usually do not measure psoriasis by PASI. The extent of psoriasis (percentage of skin body surface) is an indicator of psoriasis severity; however, there are cases when the extent may not be important, but the consequences on quality of life are important
6

(eg, face/hand/genital involvement). Therefore, we suggest considering the choice of DMARD in the light of patient-perceived severity of psoriasis (through its impact on quality of life). This would correspond in dermatological terms to moderate to severe psoriasis. Better understanding the patients perspective in PsA was set on the research agenda.

Local and systemic glucocorticoids

Glucocorticoid injections may be a useful adjunctive therapy in localised disease (oligoarticular forms, enthesitis or dactylitis).53 Intra-articular steroids are efcacious for mono/oligoarthritis or single joint ares, in otherwise well-controlled polyarthritis. Glucocorticoid injections may also be performed in dactylitis (tendon sheath/peritendinous injections) and in entheseal
Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation

Figure 1 Management of psoriatic arthritis according to the European League Against Rheumatism recommendations. Recommendations have been divided into four phases. Numbers in parentheses indicate the respective items of the recommendation as shown in table 1. Small fonts within the ellipses in phases II and III refer to dose modications or an alternative therapy, as detailed within the body of the recommendations.
Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350 7

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation
areas, for example, elbow, or retrocalcaneal bursa in Achilles enthesitis.20 Systemic steroids in psoriasis are feared, as it has been reported that skin ares may occur.54 However, the literature search performed to inform the present recommendations found few data (other than case reports) supporting the assertion that skin psoriasis may are in glucocorticoid-treated PsA patients.31 Furthermore, registry data reveal that systemic steroids are, in fact, widely used in PsA (up to 30% of patients in the German national database), usually at low doses (7.5 mg/day),55 although there is no evidence from clinical trials on the efcacy of systemic glucocorticoids in PsA (level of evidence 4; table 1). Nevertheless, the task force considered that systemic glucocoritcoids are a therapeutic option, although they should be used with caution, keeping in mind the possibility of a skin are. Greater caution should perhaps be used in patients with severe/ extensive skin involvement, and/or not taking concomitant DMARD (expert opinion). This stems partly from the observation that PASI scores in PsA trials are generally much lower than in clinical trials of psoriasis. In PsA as in other chronic diseases, the long-term use of glucocorticoids can lead to major adverse events;56 therefore, thought should be given to tapering glucocorticoids when feasible. When tapering, attention should be paid to the potential worsening of skin disease (rebound). The safety of glucocorticoids is also an important aspect of the EULAR recommendations on the management of glucocorticoid therapy.57 drugs in this recommendation.31 The list of biological agents must of course be updated regularly, as new data are published. To date, there are no data showing the superiority of TNF inhibitors in combination with synthetic DMARD versus TNF inhibitor monotherapy.3 5 31 Of note, in all trials of TNF inhibitors in PsA, methotrexate was allowed but not required, and approximately half the patients in these studies took TNF inhibitor monotherapy without concomitant methotrexate. The data for patients receiving and not receiving methotrexate were comparable.60 This was added to the research agenda. TNF inhibitors also improve enthesitis and axial disease (see also recommendations 6 and 7). Regarding the safety of biological agents in PsA, there are signicantly fewer data available than in RA.31 6163 Indeed, there are few data available regarding even the background risk of infectious disease morbidity in PsA/psoriasis. Given the paucity of safety data on biological agents in PsA, one option is to extrapolate from either the RA or psoriasis experience with these therapies. In RA, there is now a wealth of safety data from randomised controlled trials and, most importantly, from large observational studies (registry data). In comparison, however, there is a lack of long-term safety data on TNF inhibitors in the psoriasis setting. Data to date suggest that the biological agents are likely to have a similar risk prole in PsA and psoriasis with regard to serious adverse events (eg, elevated infectious risk), but that the absolute risks of infection and malignancy (and perhaps other serious adverse events) are probably lower than in RA, due to underlying pathophysiological differences between RA and psoriasis. Long-term registry or other observational data will be important to establish the safety prole of these drugs in PsA or psoriasis. However, to date, the literature review did not nd any apparent specic safety signals of concern in PsA, compared with RA. As stated in this recommendation, in patients with active arthritis, TNF inhibitors should be considered; of course, we recommend careful assessment of potential contraindications to TNF inhibitors and careful weighing of the benet/risk/cost ratio before any treatment decision is made (please see also recommendation 10, see table 1).

TNF inhibitors
This recommendation deals with patients for whom a synthetic DMARD (usually methotrexate because of its effects on joints and skin, but also leunomide, sulfasalazine or others, see above) is not efcacious or not well tolerated. A patient should be considered a treatment failure when in spite of therapy for a length of time appropriate to the drug prole (usually 36 months), the patient fails to demonstrate achievement of the treatment target low disease activity. Treatment failure could not be dened more precisely given the lack of appropriate trials. In these patients TNF inhibitor treatment (with or without continuation of previous synthetic DMARD therapy) can be considered if the disease is active, ie, if there is evidence of active arthritis in terms of swollen joints and/or at least moderate disease activity by a composite disease activity measure and/or active disease with impaired function or quality of life. However, the denition of (residual) active disease is still pending in PsA, and is part of the research agenda. This item refers to the use of biological agents. TNF inhibitors (adalimumab, etanercept, golimumab and iniximab) have demonstrated efcacy in PsA, both for skin and joint involvement, as well as in preventing radiographic damage.2 5 6 16 31 There were no evident differences regarding the efcacy of the different TNF inhibitors on the joints, although no head-to-head comparisons exist.58 However, for skin involvement, it seems that the efcacy of the TNF receptor construct etanercept on psoriasis may be lower, or at least be of slower onset, than for the antibodies targeting TNF (although there are, again, no headto-head comparisons available).2 Also, ustekinumab was tested against etanercept in patients with psoriasis and demonstrated superior skin outcomes after 12 weeks.59 This information may be taken into consideration for the choice of TNF inhibitors in patients with clinically signicant skin involvement. Other biological agents have been assessed in PsA but there were too few data (ustekinumab, rituximab, abatacept, tocilizumab) and/or too low response rates (alefacept) to consider these
8

Enthesitis and/or dactylitis and TNF inhibitors

This recommendation deals with the subgroup of patients with predominant enthesitis/dactylitis. In these patients, TNF inhibitors might be considered even if no synthetic DMARD have been tried, after failure of local or non-specic anti-inammatory therapy, because DMARD have not been proved efcacious, even though they have been little studied.31 There are very few data regarding this subgroup of patients, but the efcacy of TNF inhibitors on these manifestations of PsA has been reported in several trials, generally as secondary endpoints.31 The diagnosis of enthesitis can be challenging; several instruments have been proposed for the assessment of enthesitis.14 There is no datadriven denition of active disease in this case; we suggest to focus on quality of life in this regard. Therefore, physicians must apply clinical judgement when faced with dactylitis/enthesitis, aiming at the improvement of physical disability and quality of life, which can be severely impaired in some situations, such as enthesitis of the Achilles tendon. The group is of course not suggesting that all such patients should be treated with TNF inhibitors, as this would lead to the inappropriate use of TNF inhibitors in some situations. This recommendation, and recommendation 8, received the lowest agreement within the group (see table 1).

Axial disease and TNF inhibitors

Recommendation 7 deals with the subgroup of patients who have predominant axial disease. In these patients, TNF inhibitors
Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation
Table 2
Theme Diagnosis

Research agenda for PsA

Research questions Dening screening strategies for PsA among psoriasis patients: is screening needed and if so, how and when? Diagnosing PsA versus RA with concomitant psoriasis Dening prognostic factors related to the risk of progressive disease, structural damage and bad functional outcome in early (and established) PsA Predicting response to treatment (predicting response to NSAID, to DMARD, to biological agents) Assessment of spinal disease: dening the similarities and differences with ankylosing spondylitis Dening disease severity Dening the relationship between inammation and structural damage in PsA Exploring juvenile PsA: is it different from adult-onset PsA? Identication of new therapeutic targets Determining biomarkers related to damage, prognosis and treatment response Dening and evaluating the utility of tight control strategies in PsA Assessing efcacy and safety of combinations of DMARD and of DMARD with biological agents Evaluating the need for early treatment in PsA: who should be treated with DMARD? When to treat with DMARD? Patient-reported outcomes in PsA (which ones are important?), composite patient-reported scores in PsA, fatigue in PsA Dening treatment targets Dening (residual) active disease Dening remission and predictors of remission Need for more RCT with DMARD (eg, methotrexate) to obtain more data on efcacy and toxicity Assessing efcacy and safety of combination therapy of synthetic DMARD Need for DMARD studies in MRI-positive early axial PsA Efcacy of combining DMARD with biological agents, compared with biological monotherapy and DMARD monotherapy Dening the best indication for biological agents, when to start? Dening the optimal duration of biological therapy, including addressing biological agent discontinuation (need for respective controlled trials) Assessing the possibility of maintenance therapy with lower doses of biological agents Assessing the efcacy and toxicity of new biological agents (including more data on ustekinumab, tocilizumab, abatacept, rituximab) Through registry-based studies, assessing the safety of biological agents in PsA Assessing the risk of skin ares related to systemic glucocorticoids and in particular at low doses Assessing the benet/risk ratio of long term glucocorticoid therapy Assessing the efcacy and toxicity of intramuscular glucocorticoids in PsA Assessing the efcacy of miscellaneous drugs, for example, oral vitamin D73 74 Radiation synovectomy: evaluating its efcacy in monoarthritis of the knee Understanding the risk of cardiovascular disease in PsA and the modication of such risk according to disease activity and therapy Assessing the risk and consequences of metabolic syndrome in PsA Addressing tolerated consumption of alcohol in PsA in particular when treating by methotrexate Dening the optimal use of radiographic scores Evaluating the usefulness of MRI and ultrasonography, as well as developing scoring techniques for these imaging modalities

Prognosis

can be considered even if no synthetic DMARD have been tried. This was extrapolated from data in ankylosing spondylitis,27 which also included patients with psoriasis. In PsA, the efcacy of TNF inhibitors on axial disease has been reported only in observational studies.64 Active disease, here, refers to Bath ankylosing spondylitis disease activity index (BASDAI) levels equal to or above 4.65 66 The group suggests following established recommendations for ankylosing spondylitis.65 66

TNF inhibitors exceptionally for a very active patient naive of disease-modifying treatment
In certain, very rare and thus highly selected patients, there may be a place for TNF inhibitors as rst-line treatment. This recommendation is mere expert opinion because there are no data in this regard. In TNF inhibitor trials, some patients were in fact DMARD-naive but the results regarding efcacy and safety have never been presented separately for these patients. Some criteria to help select the patients who may need TNF inhibitors early were discussed, such as contraindications to synthetic DMARD or poor prognostic factors in conjunction with severe skin disease or severe extra-articular manifestations with a professional need for very rapid improvement. This item received the second lowest agreement and warrants further research.

Pathophysiology

Biomarkers Treatment strategy

Outcomes

Switching to another TNF inhibitor agent

This recommendation is derived from some studies indicating a good efcacy of a second TNF inhibitor in PsA.67 68 The recommendation is also extrapolated from the data available regarding switches in RA.69 To date, the group could not identify randomised trials in which switching was appropriately compared between different TNF inhibitors, and therefore a preference for a particular TNF inhibitor in this situation cannot be established.

Synthetic DMARD

Biological agents

Accounting for comorbidities and safety issues

Treatment of patients with PsA should be tailored according to the current manifestations of the disease (such as peripheral joint, skin, axial, entheseal symptoms or dactylitis), the level of current symptoms, clinical ndings and prognostic indicators; but also according to the general clinical status (age, gender, comorbidity, concomitant medications, psychosocial factors). For each treatment, a careful choice must be made, taking into account efcacy, safety and cost issues. The recommendations reect the balance of efcacy and safety and do not deal in detail with the toxicity of DMARD and biological agents. In this regard, the most important pieces of information are provided in the separate publication on the systematic literature reviews,31 which indeed are part and parcel of these recommendations, because they provide their bases. Therefore, the recommendations shown here primarily deal with agents whose toxicity appears to be manageable, assuming that users are either aware of the respective risks or will adhere to the information provided in the package inserts. When deemed of particular importance, safety issues were especially mentioned (liver toxicity on methotrexate, infections with biological agents), but clearly safety has not been comprehensively addressed. Some comorbidities require further exploration and were put on the research agenda; these include the cardiovascular risk in PsA, which has been little studied: cardiovascular diseases and their risk factors appear more common in patients with PsA than in controls.7072 The contribution of alcohol consumption, type II diabetes, obesity and steatohepatitis to hepatotoxicity in PsA is also a relevant question, particularly
9

Systemic glucocorticoids

Other systemic treatments Local treatments Comorbidities

Imaging

DMARD, disease-modifying antirheumatic drug; NSAID, non-steroidal anti-inammatory drug; PsA, psoriatic arthritis; RA, rheumatoid arthritis; RCT, randomised controlled trial.

Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation
in the light of the high prevalence of methotrexate use in this disease.50 we did not nd supportive data in this regard, and the experience of rheumatologists and dermatologists may be different, possibly related to different forms of PsA (with low to moderate skin involvement on the one hand vs important or severe skin involvement on the other). Indeed, the experts in the group did not report their patients having experienced skin ares; and registry data show us that systemic glucocorticoids are in fact widely used at low doses in PsA.55 The present EULAR recommendations have been developed by experts (mainly rheumatologists, a dermatologist, an infectious disease specialist, a health professional and two patient representatives) from 14 European countries and the USA. It is therefore a true international document, meant to serve physicians in Europe and the world, although we are aware of the fact that not all agents mentioned here are available or accessible everywhere. Beyond physicians, the document is also aimed at patients with PsA so they are informed on current treatment goals, strategies and opportunities. Importantly, patient representatives also participated in the task force. Finally, this document is also meant to inform ofcials in governments, social security agencies and reimbursement agencies. The recommendations on the management of PsA provided here by the EULAR task force, when compared with those provided by GRAPPA,20 are of lesser complexity and thus more easy to adhere to; moreover, they cover additional aspects of drug therapies as well as therapeutic strategies and goals. A graphic representation (see gure 1) captures most of the important items. The limitations of the present recommendations include that juvenile PsA and patients with psoriasis and some joint pain but without a denitive diagnosis of PsA are outside their scope; that topical treatments including topical NSAID and topical steroids are not taken into account and that non-pharmacological therapy is not considered. However, the group did state that non-pharmacological therapy was an important component of PsA treatment. These recommendations reect the current state of evidence and thought in the area of PsA management. The ve overarching principles and 10 practical recommendations have a high level of face validity and feasibility, and the development of a scientic agenda will guide future research. However, several of the recommendations are strongly based on expert opinion, which in turn is based on clinical practice that has emerged in certain institutions, rather than available evidence. This is due to the paucity of data in the eld of PsA. Therefore, the research agenda developed is extensive. Finally, as has been the case over the past decade, it is to be anticipated that new data on existing or new drugs or therapeutic strategies will emerge over the next few years. Therefore, we will carefully observe the developments in the eld and assume that an amendment of these recommendations may be needed in 25 years.
Funding This study was supported by EULAR. Competing interests The following authors declare that they have no potential conict of interest: CG-V, ZA, HD, MM, DB. The following authors declare a potential conict of interest having received grant support and/or honoraria for consultations and/or for presentations as indicated: LG: Abbott, BMS, Chugai, MSD, Pzer, Roche, Schering-Plough, UCB, Wyeth; JSS: Abbott, BMS, Chugai, MSD, Pzer, Roche, Sano-Aventis, Schering-Plough, UCB, Wyeth; HM-O: Abbott, Centocor, Chugai, MSD, Pzer; DVDH:Abbott, Amgen, Astra Zeneca, BMS, Centocor, Chugai, Eli lilly, GSK, Merck, Novartis, Otsuka, Pzer, Roche, Schering-Plough, UCB, Wyeth; OF: Abbott, BMS, Pzer, Merck, UCB; DA: Abbott, Roche, Schering-Plough, BMS, UCB, Sano-Aventis; MB: Roche, Abbott, BMS, Wyeth; PB: Abbott, Pzer, Roche, Sonobite, Wyeth; JB: Abbott, Centocor,Chugai, Merck, MSD, Novartis, Pzer, Roche, UCB; FCB: Abbott, Schering-Plough, Wyeth; GB: Abbott, BMS, Chugai, MSD, Pzer, Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

Graphic representation of the recommendations

The recommendations and the algorithm they imply are summarised in gure 1. The gure attempts to capture the most important aspects of the recommendations and explanatory text. While it does not account for all therapeutic eventualities nor ought to be representative for all variations of the disease, the relatively high level of agreement obtained within the group (see supplementary text 3, available online only) suggests that it has validity for a large majority of patients with PsA.

Research agenda
One of the objectives of this initiative was to develop a research agenda, to guide future research funding by EULAR. An extensive research agenda was developed and the summary is presented in table 2.

DISCUSSION
The task force has formulated 10 statements on the management of PsA. These statements were based on systematic literature reviews, but also on expert opinion with subsequent consensus nding on the wording of the recommendations. By this process and by stating the respective levels of evidence and strength of recommendation for each item, the committee adhered to the EULAR standardised operating procedures for the development of recommendations. Moreover, when evidence was lacking and the task force had to use only expert opinion, a research agenda was formulated to expedite the generation of evidence in the future. The reasoning behind each statement and, particularly, behind the recommendations specic wordings is explained in detail in the Results section. Importantly, the overall agreement with these statements, assessed anonymously several weeks after their formulation, was very high. It is worth noting that the task force felt the best evidence for efcacy was available for three synthetic DMARD (methotrexate, leunomide and sulfasalazine; statement 2) and four TNF inhibitors (adalimumab, etanercept, golimumab, iniximab; statements 57). Some additional synthetic DMARD agents are mentioned in the text only, because although effective in RA, their efcacy appeared to be lower or toxicity higher than that of other agents in their general class, and the data were often sparse. The task force was convinced that modern therapy of PsA should be target oriented and governed by a strategic treatment approach. Remission or at least low disease activity, if remission cannot be attained, was afrmed as the therapeutic goal, in line with recommendations in RA.30 However, the literature review found few data regarding the natural history, prognosis, treatment targets and treatment strategies in PsA,31 contrary to the situation in RA. Still, there are some data supporting low disease activity or minimal disease activity as a therapeutic goal.7579 Furthermore, monotherapy with all TNF inhibitors usually leads to complete cessation of erosion progression at the group level; these agents appear to induce an arrest in disease progression.31 Finally, treatment targets constitute yet another part of the research agenda. Glucocorticoids had a special place in the discussion (statement 4). Although there is a fear of psoriasis ares related to systemic glucocorticoids in PsA (and especially their cessation),
10

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation
Roche, Sano-Aventis, Schering Plough, UCB, Wyeth; JDC: Abbott, BMS, MSD, Roche; MdeW: Abbott, Roche, Wyeth; KdeV: Abbott, BMS, Celgene, Novartis, Pzer, UCB; MD: Abbott, BMS, Novartis, Nordic Pharma, Pzer, Roche, UCB, Wyeth; PH: Abbott, BMS, Pzer, Schering Plough, UCB, Wyeth; AK: Abbott, Amgen, Centocor, Roche, UCB; TKK: Abbott, BMS, MSD, Pzer, Roche, UCB; RL: Abbott, Amgen, BMS, Centocor, Merck, Pzer, Schering-Plough, UCB, Wyeth; TL: Abbott, Almirall-Hermal, Basilea, BiogenIdec, Ceries, Galderma, Innov, Janssen-Cilag, Leo Pharma, Maruho, MSD, Novartis, Palau Pharma, Pzer, Shionogi, Symrise, Wolff; DMcG: Merck, Pzer, Roche, Schering-Plough, Wyeth; INMcH: Abbott, Schering-Plough; IBMcI: Abbott, BMS, Merck, Pzer, Roche; CR: Abbott, Amgen, BMS, Centocor, Pzer, UCB; JS: Abbott, BMS, Centocor, MSD, Pzer, Roche, Sano-Aventis, UCB; PPT: Abbott, Amgen, Centocor, Pzer, Schering-Plough, Wyeth; GV: Abbott, BMS, Roche, MSD, Schering-Plough, UCB, Wyeth; JV: Abbott, BMS, MSD, Pzer, Roche, UCB; KLW: Genentech, Wyeth; AZ: Abbott, Amgen, BMS, Essex/Schering-Plough, Merck, Pzer, Roche, Sano-Aventis, UCB, Wyeth; PE: Abbott, BMS, Centocor, Pzer, Roche, SanoAventis, Schering-Plough,UCB, Wyeth. Provenance and peer review Not commissioned; externally peer reviewed. Author af liations 1Paris Descartes University, Paris, France 2APHP, Rheumatology B Department, Cochin Hospital, Paris, France 3Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria 42nd Department of Medicine, Hietzing Hospital, Vienna, Austria 5Paris 6 Pierre et Marie Curie University, Paris, France 6Department of Rheumatology, Piti-Salptrire Hospital, Paris, France 7Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK 8NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK 9Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands 10Department of Rheumatology, St Vincents University Hospital and Conway Institute, University College Dublin, Dublin, Ireland 113rd Rheumatology Department, National Institute of Rheumatology and Physiotherapy, Budapest, Hungary 12Rheumatology, Clinical Immunology and Allergy, University of Crete, Faculty of Medicine, Heraklion, Greece 13Rheumazentrum Ruhrgebiet, Herne and Ruhr-Universitt Bochum, Bochum, Germany 14Department of Rheumatology and Clinical Immunology, Charit University Medicine, Berlin, Germany 15Arthritis Unit, Department of Rheumatology, Hospital Clnic and IDIBAPS, Barcelona, Spain 16People with Arthritis/Rheumatism in Europe (PARE), Zurich, Switzerland 17Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway 18Faculty of Medicine, University of Oslo, Oslo, Norway 19Department of Rheumatology, University Hospitals, Leuven, Belgium 20Division of Rheumatology, Allergy, Immunology, University of California, San Diego, California, USA 21Department of Internal Medicine/Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands 22Department of Dermatology, University Hospital Mnster, Mnster, Germany 23A.DI.PSO. (Associazione per la Difesa degli Psoriasici) PE.Pso.POF (Pan European Psoriasis Patients Organization Forum), Rome, Italy 24Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, UK 25Institute of Infection, Immunity and Inammation, University of Glasgow, Glasgow, UK 26Allergy, Immunology and Rheumatology Division, University of Rochester Medical Center, Rochester, New York, USA 27Rheumatology, Campus Benjamin Franklin, Charit, Berlin, Germany 28Division of Clinical Immunology and Rheumatology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands 29Department of Internal Medicine/ Rheumatology Unit, La Sapienza University of Rome, Rome, Italy 30Institute of Rheumatology, Prague, Czech Republic 31Department of Infectious Diseases, Public Health and Preventive Medicine, Oregon Health and Science University, Portland, Oregon, USA 32German Rheumatism Research Centre, Berlin, Germany 33Department of Rheumatology and Clinical Immunology, Charit University Medicine Berlin, Berlin, Germany
2. 3. 4. Mease PJ, Goffe BS, Metz J, et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000;356:38590. Antoni C, Krueger GG, de Vlam K, et al. Iniximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis 2005;64:11507. Kaltwasser JP, Nash P, Gladman D, et al. Efcacy and safety of leunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 2004;50:193950. Mease PJ, Gladman DD, Ritchlin CT, et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005;52:327989. Kavanaugh A, McInnes I, Mease P, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efcacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009;60:97686. Mease PJ, Gladman DD, Keystone EC. Alefacept in combination with methotrexate for the treatment of psoriatic arthritis: results of a randomized, double-blind, placebocontrolled study. Arthritis Rheum 2006;54:163845. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009;61:45185. Jones G, Crotty M, Brooks P. Interventions for psoriatic arthritis. Cochrane Database Syst Rev 2000;3:CD000212. Gottlieb A, Menter A, Mendelsohn A, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebocontrolled, crossover trial. Lancet 2009;373:63340. Peeters AJ, Dijkmans BA, van der Schroeff JG. Fumaric acid therapy for psoriatic arthritis. A randomized, double-blind, placebo-controlled study. Br J Rheumatol 1992;31:5024. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol 2010;62:11435. Wright V, Moll JM. Psoriatic arthritis. Bull Rheum Dis 1971;21:62732. Van den Bosch F, Cryssen BV, Mielants H. Clinical assessment in the spondyloarthropathies, including psoriatic arthritis. Curr Opin Rheumatol 2006;18:3548. McGonagle D, Conaghan PG, Emery P. Psoriatic arthritis: a unied concept twenty years on. Arthritis Rheum 1999;42:10806. Antoni CE, Kavanaugh A, Kirkham B, et al. Sustained benets of iniximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the iniximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum 2005;52:122736. Gladman DD, Mease PJ, Ritchlin CT, et al. Adalimumab for long-term treatment of psoriatic arthritis: forty-eight week data from the adalimumab effectiveness in psoriatic arthritis trial. Arthritis Rheum 2007;56:47688. Gladman DD, Mease PJ, Cifaldi MA, et al. Adalimumab improves joint-related and skin-related functional impairment in patients with psoriatic arthritis: patient-reported outcomes of the Adalimumab Effectiveness in Psoriatic Arthritis Trial. Ann Rheum Dis 2007;66:1638. Furst DE, Keystone EC, Fleischmann R, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis 2010;69(Suppl 1):i229. Ritchlin CT, Kavanaugh A, Gladman DD, et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis 2009;68:138794. Kavanaugh AF, Ritchlin CT. Systematic review of treatments for psoriatic arthritis: an evidence based approach and basis for treatment guidelines. J Rheumatol 2006;33:141721. Fraser AD, van Kuijk AW, Westhovens R, et al. A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis. Ann Rheum Dis 2005;64:85964. Gladman DD, Mease PJ, Healy P, et al. Outcome measures in psoriatic arthritis. J Rheumatol 2007;34:115966. Nash P. Assessment and treatment of psoriatic spondylitis. Curr Rheumatol Rep 2009;11:27883. Gladman DD, Landew R, McHugh NJ, et al. Composite measures in psoriatic arthritis: GRAPPA 2008. J Rheumatol 2010;37:45361. Dougados M, Betteridge N, Burmester GR, et al. EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees. Ann Rheum Dis 2004;63:11726. Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006;65:44252. Zhang W, Doherty M, Arden N, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing

5.

6.

7.

8.

9. 10.

11.

12.

13. 14.

15. 16.

17.

18.

19.

20. 21.

22.

23. 24. 25. 26.

27.

REFERENCES
1. Kavanaugh A, Antoni CE, Gladman D, et al. The Iniximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): results of radiographic analyses after 1 year. Ann Rheum Dis 2006;65:103843. 28.

Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

11

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Recommendation
Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2005;64:66981. Combe B, Landewe R, Lukas C, et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007;66:3445. Smolen JS, Landew R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010;69:96475. Ash Z,. A systematic literature review of conventional and biologic drug therapies for the treatment of psoriatic arthritis: current evidence informing the EULAR recommendations for the management of Psoriatic Arthritis. Ann Rheum Dis. Kivitz AJ, Espinoza LR, Sherrer YR, et al. A comparison of the efcacy and safety of celecoxib 200 mg and celecoxib 400 mg once daily in treating the signs and symptoms of psoriatic arthritis. Semin Arthritis Rheum 2007;37:16473. Sarzi-Puttini P, Santandrea S, Boccassini L, et al. The role of NSAIDs in psoriatic arthritis: evidence from a controlled study with nimesulide. Clin Exp Rheumatol 2001;19(1 Suppl 22):S1720. Borer JS, Simon LS. Cardiovascular and gastrointestinal effects of COX-2 inhibitors and NSAIDs: achieving a balance. Arthritis Res Ther 2005;7(Suppl 4):S1422. Latimer N, Lord J, Grant RL, et al. Cost effectiveness of COX 2 selective inhibitors and traditional NSAIDs alone or in combination with a proton pump inhibitor for people with osteoarthritis. BMJ 2009;339:b2538. Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal antiinammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet 2007;370:213851. Gladman DD, Farewell VT. Progression in psoriatic arthritis: role of time varying clinical indicators. J Rheumatol 1999;26:240913. Lard LR, Visser H, Speyer I, et al. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 2001;111:44651. Scarpa R, Peluso R, Atteno M, et al. The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: results of a pilot randomised 6-month trial with methotrexate. Clin Rheumatol 2008;27:8236. Lie E, van der Heijde D, Uhlig T, et al. Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis. Ann Rheum Dis 2010;69:6716. Black RL, OBrien WM, Vanscott EJ, et al. Methotrexate therapy in psoriatic arthritis; double-blind study on 21 patients. JAMA 1964;189:7437. Willkens RF, Williams HJ, Ward JR, et al. Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Arthritis Rheum 1984;27:37681. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 2009;68:10949. Fraser SM, Hopkins R, Hunter JA, et al. Sulphasalazine in the management of psoriatic arthritis. Br J Rheumatol 1993;32:9235. Gupta AK, Grober JS, Hamilton TA, et al. Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial. J Rheumatol 1995;22:8948. Salvarani C, Macchioni P, Olivieri I, et al. A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis. J Rheumatol 2001;28:227482. Clark CM, Kirby B, Morris AD, et al. Combination treatment with methotrexate and cyclosporin for severe recalcitrant psoriasis. Br J Dermatol 1999;141:27982. Helliwell PS, Taylor WJ. Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs comparison of drugs and adverse reactions. J Rheumatol 2008;35:4726. Whiting-OKeefe QE, Fye KH, Sack KD. Methotrexate and histologic hepatic abnormalities: a meta-analysis. Am J Med 1991;90:71116. Curtis JR, Beukelman T, Onofrei A, et al. Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leunomide. Ann Rheum Dis 2010;69:437. Rosenberg P, Urwitz H, Johannesson A, et al. Psoriasis patients with diabetes type 2 are at high risk of developing liver brosis during methotrexate treatment. J Hepatol 2007;46:111118. Heydendael VM, Spuls PI, Opmeer BC, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med 2003;349:65865. Eder L, Chandran V, Ueng J, et al. Predictors of response to intra-articular steroid injection in psoriatic arthritis. Rheumatology (Oxford) 2010;49:136773. Fredriksson T, Pettersson U. Severe psoriasis oral therapy with a new retinoid. Dermatologica 1978;157:23844. Zink A, Thiele K, Huscher D, et al. Healthcare and burden of disease in psoriatic arthritis. A comparison with rheumatoid arthritis and ankylosing spondylitis. J Rheumatol 2006;33:8690. 56. Hoes JN, Jacobs JW, Verstappen SM, et al. Adverse events of low- to mediumdose oral glucocorticoids in inammatory diseases: a meta-analysis. Ann Rheum Dis 2009;68:18338. Hoes JN, Jacobs JW, Boers M, et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 2007;66:15607. Glintborg B, Ostergaard M, Dreyer L, et al. Treatment response, drug survival and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor a therapy: Results from the Danish nationwide DANBIO registry. Arthritis Rheum 2011;63:38290. Grifths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 2010;362:11828. Heiberg MS, Koldingsnes W, Mikkelsen K, et al. The comparative one-year performance of anti-tumor necrosis factor alpha drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study. Arthritis Rheum 2008;59:23440. Mease PJ, Ory P, Sharp JT, et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT). Ann Rheum Dis 2009;68:7029. Mease PJ, Kivitz AJ, Burch FX, et al. Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. J Rheumatol 2006;33:71221. Antoni CE, Kavanaugh A, van der Heijde D, et al. Two-year efcacy and safety of iniximab treatment in patients with active psoriatic arthritis: ndings of the Iniximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT). J Rheumatol 2008;35:86976. Olivieri I, de Portu S, Salvarani C, et al. The psoriatic arthritis cost evaluation study: a cost-of-illness study on tumour necrosis factor inhibitors in psoriatic arthritis patients with inadequate response to conventional therapy. Rheumatology (Oxford) 2008;47:166470. Braun J, Davis J, Dougados M, et al. First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis 2006;65:31620. Braun J, Pham T, Sieper J, et al. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 2003;62:81724. Gomez-Reino JJ, Carmona L. Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period. Arthritis Res Ther 2006;8:R29. Saad AA, Ashcroft DM, Watson KD, et al. Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register. Arthritis Res Ther 2009;11:R52. Nam JL, Winthrop KL, van Vollenhoven RF, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis 2010;69:97686. Han C, Robinson DW, Jr , Hackett MV, et al. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol 2006;33:216772. Peters MJ, Symmons DP, McCarey D, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inammatory arthritis. Ann Rheum Dis 2010;69:32531. Tam LS, Tomlinson B, Chu TT, et al. Cardiovascular risk prole of patients with psoriatic arthritis compared to controls the role of inammation. Rheumatology (Oxford) 2008;47:71823. Gal J, Lakos G, Szodoray P, et al. Immunological and clinical effects of alphacalcidol in patients with psoriatic arthropathy: results of an open, follow-up pilot study. Acta Derm Venereol 2009;89:1404. Huckins D, Felson DT, Holick M. Treatment of psoriatic arthritis with oral 1,25dihydroxyvitamin D3: a pilot study. Arthritis Rheum 1990;33:17237. Saber TP, Ng CT, Renard G, et al. Remission in psoriatic arthritis: is it possible and how can it be predicted? Arthritis Res Ther 2010;12:R94. Cantini F, Niccoli L, Nannini C, et al. Criteria, frequency, and duration of clinical remission in psoriatic arthritis patients with peripheral involvement requiring secondline drugs. J Rheumatol Suppl 2009;83:7880. Kavanaugh A, Fransen J. Dening remission in psoriatic arthritis. Clin Exp Rheumatol 2006;24(6 Suppl 43):S837. Coates LC, Cook R, Lee KA, et al. Frequency, predictors, and prognosis of sustained minimal disease activity in an observational psoriatic arthritis cohort. Arthritis Care Res (Hoboken) 2010;62:9706. Coates LC, Fransen J, Helliwell PS. Dening minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis 2010;69:4853.

29.

57.

30.

58.

31.

59.

32.

60.

33.

34. 35.

61.

62.

36.

63.

37. 38.

64.

39.

65.

40.

66.

41. 42.

67.

43.

68.

44. 45.

69.

46.

70.

47.

71.

48.

72.

49. 50.

73.

74. 75. 76.

51.

52.

77. 78.

53. 54. 55.

79.

12

Ann Rheum Dis 2012;71:412. doi:10.1136/annrheumdis-2011-200350

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies
L Gossec, J S Smolen, C Gaujoux-Viala, et al. Ann Rheum Dis 2012 71: 4-12 originally published online September 27, 2011

doi: 10.1136/annrheumdis-2011-200350

Updated information and services can be found at:

http://ard.bmj.com/content/71/1/4.full.html

These include:

Data Supplement References

"Web Only Data"

http://ard.bmj.com/content/suppl/2011/09/27/annrheumdis-2011-200350.DC1.html

This article cites 78 articles, 40 of which can be accessed free at:

http://ard.bmj.com/content/71/1/4.full.html#ref-list-1

Article cited in:

http://ard.bmj.com/content/71/1/4.full.html#related-urls

Open Access Email alerting service

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.

Topic Collections

Articles on similar topics can be found in the following collections Unlocked (214 articles) Biological agents (330 articles) Drugs: musculoskeletal and joint diseases (449 articles) Degenerative joint disease (2941 articles) Musculoskeletal syndromes (3165 articles)

To request permissions go to:

http://group.bmj.com/group/rights-licensing/permissions

To order reprints go to:

http://journals.bmj.com/cgi/reprintform

To subscribe to BMJ go to:

http://group.bmj.com/subscribe/

Downloaded from ard.bmj.com on May 1, 2012 - Published by group.bmj.com

Notes

To request permissions go to:

http://group.bmj.com/group/rights-licensing/permissions

To order reprints go to:

http://journals.bmj.com/cgi/reprintform

To subscribe to BMJ go to:

http://group.bmj.com/subscribe/