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Therapeutics


should be coordinated between patients, rheumatologists and dermatologists and also with other specialists as needed. The main goal when treating PsA is remission, or at least a state of prolonged minimal disease activity, in order to maximise long-term health-related quality of life and social participation through control of signs and symptoms, prevention of structural damage, normalisation or preservation of function, avoidance of toxicities and minimisation of comorbidities (Figure 1). This implies a treatment to target approach, that is, measuring disease activity regularly and adjusting therapy accordingly.10,11


Traditional systemic oral drugs First-line therapy in PsA includes the use of anti-inflammatory agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), and, at times, low-dose glucocorticoids (GCs) given orally or by intra-articular injections. Although NSAIDs are the first step to treat signs and symptoms of PsA, these drugs are preferred for mild cases.9,10,12,13


Limited


data on efficacy are available for azathioprine, chloroquine, D-penicillamine, fumaric acid and colchicine.12


1. Early recognition of psoriatic arthritis: Screening questionnaires Dermatology/rheumatology clinics


Educational tools for non-rheumatologists and patients


2. Evaluate disease severity in each domain: Arthritis: peripheral/axial Enthesitis Dactylitis Nail/skin


Cardiovascular comorbidity


3. Therapeutic goals: Remission


Prolonged minimal disease activity Use drugs with high benefit-to-risk ratio


4. Evaluate disease activity and therapeutic goals regularly: Treat to target


Figure 1: Principles of treatment for psoriatic arthritis Gold salts have shown some


efficacy to treat peripheral PsA but these compounds do not appear to be effective for the treatment of psoriasis.12


Therefore


we will focus only on effectiveness of methotrexate (MTX), leflunomide (LEF), sulphasalazine (SSZ) and cyclosporin (CsA).


Methotrexate


Although there is limited clinical trial evidence for MTX efficacy in PsA, several disease registries in Europe and the USA show MTX to be the most commonly used disease-modifying anti-rheumatic drugs (DMARDs) in PsA.13


The


Methotrexate in Psoriatic Arthritis (MIPA) study, one of the most important randomised controlled trials (RCTs) conducted so far with MTX, concluded that there was insufficient evidence to support the use of MTX as a standard treatment for PsA.14


However, several 4


design limitations (high dropout rate, channelling bias, low goal dose, etc.) of this study, as well as evidence coming from other studies, do not support such conclusion. For example, in the Remicade Study in Psoriatic Arthritis Patients Of Methotrexate-Naïve Disease (RESPOND) study that compared MTX alone versus MTX plus infliximab in 115 PsA patients with a relatively short


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duration of disease, ACR20 response was achieved by 86.3% in the combined arm and 66.7% in the MTX arm. In this study, more than 50% of patients treated with MTX alone had a PASI75 response.15


Summary of the results of


eight non-randomised observational studies of MTX use in PsA reported clinical improvement in joint and skin assessments, pain, morning stiffness and acute phase reactants.16


Another


Data on radiographic progression of MTX have not been conclusive as it was only analysed in a small case-control study. However, an important factor to be mentioned is how we use MTX in PsA. In the University of Toronto PsA registry, investigators demonstrated that patients exposed to higher doses of MTX (average 16.2mg/week) had a greater reduction in tender and swollen joint count, and better Psoriasis Area and Severity Index (PASI) responses compared with those with lower doses (average 10.8mg/week). The radiographic progression score was also lower in the high-dose group compared with the low-dose arm.17


advantage of MTX is its high retention rate.13


Therefore, MTX


does have a beneficial clinical effect on peripheral PsA and psoriasis, but there is lack of data about its impact on important clinical domains such as enthesitis, dactylitis and spondylitis.12,13


Leflunomide


The 24-week RCT comparing LEF monotherapy versus placebo (TOPAS study) concluded that LEF was clinically effective for the treatment of peripheral arthritis and psoriasis.12,13


However, there


is actually no information regarding efficacy of this drug on other PsA domains. Information in terms of radiographic progression is also scant. In a recent LEF observational study, 86.4% of 440 patients achieved a psoriatic arthritis response criteria (PsARC) response at 24 weeks. Significant improvements were observed in tender and swollen joint counts, patient and physician global assessments, fatigue, pain, skin disease, dactylitis and nail lesions. There was also a low discontinuation rate of 12.3% with only three drug reactions labelled as serious (two increased liver enzymes; one hypertensive crisis).18


Therefore, LEF


seems to be an effective and well-tolerated option for PsA in daily clinical practice.


Sulphasalazine


Although the precise mechanism of action of SSZ is unknown, it is thought to have anti-inflammatory effects mediated through inhibition of the 5-lipoxygenase pathway. SSZ is one of the most studied drugs in PsA, with seven RCTs (doses from 500 to 3000mg/day) including more than


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