During the course of this PhD, additional studies have confirmed a high sensitivity and specificity of the CASPAR criteria in established PsA in a variety of populations (Congi and Roussou 2010; Leung et al. 2010). However, no further studies evaluating the use of classification or diagnostic criteria, such as the CASPAR criteria, have been published in early disease. No other potential diagnostic or classification criteria have been suggested. Work in the current literature aiming to identify PsA early has concentrated on the use of screening tools, particularly aimed at dermatology clinics.
There are four PsA screening tools available; the Psoriatic Arthritis Questionnaire (PAQ) (Alenius et al. 2002), the Psoriatic Arthritis Screening and Evaluation tool (PASE) (Husni et al. 2007), the Toronto Psoriatic Arthritis Screening tool (ToPAS) (Gladman et al. 2009) and the Psoriasis Epidemiology Screening Tool (PEST) (Ibrahim et al. 2009a). All are paper-based questionnaires with 5-15 questions designed for completion by the patient prior to their dermatology appointment. All have been tested in dermatology clinics and found to be sensitive and specific as screening tools for arthritis. Some of the questionnaires have also been used in other settings such as UK general practice populations and US family medicine clinics. These screening tools can then be used as a brief intervention by dermatologists or primary care physicians to identify which patients should be referred to a rheumatologist. A head-to-head study comparing three of these questionnaires (PASE, ToPAS and PEST) in dermatology clinics is currently underway in the UK with the aim of identifying which tool performs the best (Helliwell 2010). Patients in the study will then be assessed by a physician for the presence of PsA and will also have the CASPAR criteria applied as classification criteria. This will allow further validation of the CASPAR criteria compared to physician diagnosis in an independent national cohort of newly diagnosed PsA.
8.1.2
Novel composite outcome measures in PsA
The MDA criteria developed as part of this PhD have also been assessed in the current literature by other groups. In particular, analyses of adalimumab clinical trials have looked at the proportion of patients achieving MDA in the ADEPT study (Mease et al. 2009b). The authors reported a significant difference in the proportion of patients achieving MDA after treatment with adalimumab when compared to placebo (p<0.001) in keeping with the results of the analysis of the IMPACT and IMPACT2 studies shown in Chapter Six. Interestingly, the authors of the ADEPT study have also proposed a modification to use an alternative psoriasis measure.
The original MDA criteria were developed for use with either BSA or PASI score. The researchers from the ADEPT study have suggested the use of the physicians global assessment (PGA) of psoriasis score of “clear” or “nearly clear” as a cut point for MDA in the skin domain and have analysed this again in the ADEPT data (Mease et al. 2010). This may be particularly useful in patients with little skin psoriasis where PASI in particular can be misleading. It also makes the tool more feasible for routine clinical use as the PGA is quick to complete.
Over the duration of this thesis, there has been significant work in the development of composite disease activity measures for psoriatic arthritis. The CPDAI uses a grid system to assess disease activity in each of the five domains of PsA (arthritis, skin disease, enthesitis, dactylitis, axial disease) and this can be summed to a disease activity score (Mumtaz et al. 2010). The DAPSA (originally the DAREA) is a composite measure of peripheral arthritis activity validated in PsA following its original development in reactive arthritis (Nell-Duxneuner et al. 2010). Both of these are summarised in section 2.3.1.6. Ongoing work under the umbrella of the OMERACT PsA and GRAPPA groups is providing more evidence comparing these existing measures of disease activity. There is data to support the use of the CPDAI and DAPSA within the GRACE dataset and from retrospective analyses of clinical trials. Both perform well but the DAPSA is recognised as a peripheral arthritis measure only; there is no attempt to quantify disease activity in the other domains of PsA. There is also work developing a novel composite index using data from the GRACE initiative (Coates et al. 2010c).
The advantages of the CPDAI, DAPSA and future GRACE composite measures in comparison to that of MDA, is that they allow assessment of a full range of disease activity rather than one particular state. In the future, potential cut offs could be defined for these measures to define remission, low disease activity and high disease activity. However, at present, there are no other proposed definitions of disease states and therefore nothing that could be used as a target for treatment.
8.1.3
Novel treatment regimens in PsA
Investigation of treatment algorithms for PsA is still in its infancy. To date, there have been few studies comparing different treatment algorithms, with the majority of studies concentrating on proving the efficacy of individual drugs against placebo. A small open label study attempted to address the issue of immediate vs delayed prescription of DMARDs. This showed a significant difference at 12 weeks after the differing treatment regimens but did not show any prolonged benefit once the delayed group had commenced on methotrexate (Scarpa et al. 2008b). One study, the RESPOND study, has compared methotrexate vs infliximab for early PsA
(Nasonov et al. 2009) but this study was open label and is likely to be affected by bias introduced by this study design.
There is growing interest in the investigation of optimal treatment for patients with PsA, and the TICOPA study should provide significant insight regarding treatment outcomes with tight control of disease activity. The study is recruiting at six UK sites. It is estimated that recruitment will be complete by July 2011 with results in available in 2012. The comprehensive outcome measures included in the blinded assessments may also shed some light onto the efficacy of synthetic DMARDs in PsA, particularly in less researched domains such as enthesitis and dactylitis.