The Future of Treatment for Psoriatic Arthritis
The Future of Treatment for Psoriatic Arthritis
As the GRAPPA and EULAR treatment recommendations highlight, the targets of treatment have not been defined, nor is the evidence surrounding putative targets extensive. Evidence analyzed retrospectively from the IMPACT and IMPACT2 trials on infliximab versus placebo demonstrated that attainment of minimal disease activity, as defined by Coates et al. (which requires the presence of at least five out of the following seven domains: tender joint count ≤1, swollen joint count ≤1, PASI ≤1 or body surface area ≤3%, tender entheseal points ≤1, HAQ score ≤0.5, patient global disease activity visual analogue scale (VAS) score ≤20 and patient pain VAS ≤15) is associated with a significant reduction in radiographic progression, while evidence from the University of Toronto Psoriatic Arthritis Clinic revealed that sustaining minimal disease activity over 12 months resulted in significantly less clinical joint damage. However, prospective studies examining such outcomes are absent. In that regard, an international group of rheumatologists from Europe and North America convened to provide evidence-based recommendations based on a 'treat-to-target' concept that has been successfully employed in other diseases, including RA.
After identifying and reviewing the available evidence pertaining to 'treating-to-target' in PsA, the international group published their definitions of the treatment targets in both PsA and ankylosing spondylitis. Clinical remission of the musculoskeletal components of spondyloarthritis (SpA; arthritis, spondylitis, enthesitis and dactylitis) was identified as the main treatment goal, and defined by the authors as the "absence of clinical and laboratory evidence of significant inflammatory disease activity" followed by attainment of minimal disease activity if remission was not achieved; however, the authors noted that, currently, there is no definitive evidence that remission leads to a better long-term outcome than maintenance of low disease activity. The 'overarching principles' in the application of treatment for SpA, including PsA, include shared decision-making between the patient and rheumatologist, involvement of other specialists relevant to the extra-articular manifestations of SpA, such as dermatologists and gastroenterologists, and maintenance of quality of life for all patients.
Clearly, the evidence base to support the targets of treatment needs to be expanded, and future treatment of PsA will be dependent on acquisition of this evidence base. Interestingly, the recommendations listed above do not advocate the assessment of PsA patients at the earliest time point in the course of their disease, yet there is evidence to suggest that earlier presentation in the disease course is associated with better clinical and radiographic outcomes and the establishment of early arthritis clinics to accommodate early PsA could have a prognostic benefit on the course of PsA.
The TICOPA protocol study will provide important data in that regard. This study, inspired by the TICORA study in RA, is a UK-based, open-label, randomized controlled study examining clinical and radiographic outcome (ACR20, 50 and 70 response, PASI scores, change in enthesitis and dactylitis scores, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index and change in Sharp/van der Heijde scores) in those randomized to receive either standard care or intensive management in patients with early, treatment-naive PsA. The treatment target in those receiving intensive management will be minimal disease activity, as defined by Coates et al..
Treatment of psoriatic disease according to prespecified targets will be the basis of all future therapeutic regimens. The pursuit of disease control, however, will need to account for individual patient needs and the heterogeneity of the PsA population as a whole, including susceptibility to treatment toxicity and adverse events.
There have been few studies comparing the efficacy of medication combinations in PsA, unlike, for example, the BeSt trial in RA. The BeSt study is a single-blind, multicenter randomized trial comparing four different treatment strategies in patients (n = 508) with early RA (<2 years disease duration) with a predefined treatment target of a DAS28 score ≤2.4, with clinical evaluation at 3-month intervals. This trial has accumulated prospective data over 7 years and has informed rheumatologists that early and aggressive disease control results in less radiographic damage and functional decline over time, even allowing for DMARD/TNFi discontinuation and drug-free remission.
Applying a similar treatment strategy to PsA would be of enormous interest to rheumatologists. Given the lower prevalence of PsA compared with RA; however, international collaboration would be required to attain adequate numbers to sufficiently power the study. In such an instance, GRAPPA may play a central role.
There are limited data regarding the use of DMARD and TNFi in the treatment of oligoarthritis, enthesitis and dactylitis; however, the initial clinical trials with TNFi showed that infliximab and golimumab have efficacy in treatment of enthesitis, dactylitis and psoriasis, while golimumab has also been shown to improve nail disease in psoriasis.
Treatment recommendations for predominantly axial disease in PsA, however, are based on observational studies in the PsA population and also extrapolated data from ankylosing spondylitis patients with psoriasis.
Future studies need to focus on all the musculoskeletal and cutaneous manifestations of psoriatic disease, with predefined criteria for disease activity in each domain, with applicable and validated outcome measures.
Treatment Targets & Strategies
'Treating-to-target' in PsA
As the GRAPPA and EULAR treatment recommendations highlight, the targets of treatment have not been defined, nor is the evidence surrounding putative targets extensive. Evidence analyzed retrospectively from the IMPACT and IMPACT2 trials on infliximab versus placebo demonstrated that attainment of minimal disease activity, as defined by Coates et al. (which requires the presence of at least five out of the following seven domains: tender joint count ≤1, swollen joint count ≤1, PASI ≤1 or body surface area ≤3%, tender entheseal points ≤1, HAQ score ≤0.5, patient global disease activity visual analogue scale (VAS) score ≤20 and patient pain VAS ≤15) is associated with a significant reduction in radiographic progression, while evidence from the University of Toronto Psoriatic Arthritis Clinic revealed that sustaining minimal disease activity over 12 months resulted in significantly less clinical joint damage. However, prospective studies examining such outcomes are absent. In that regard, an international group of rheumatologists from Europe and North America convened to provide evidence-based recommendations based on a 'treat-to-target' concept that has been successfully employed in other diseases, including RA.
After identifying and reviewing the available evidence pertaining to 'treating-to-target' in PsA, the international group published their definitions of the treatment targets in both PsA and ankylosing spondylitis. Clinical remission of the musculoskeletal components of spondyloarthritis (SpA; arthritis, spondylitis, enthesitis and dactylitis) was identified as the main treatment goal, and defined by the authors as the "absence of clinical and laboratory evidence of significant inflammatory disease activity" followed by attainment of minimal disease activity if remission was not achieved; however, the authors noted that, currently, there is no definitive evidence that remission leads to a better long-term outcome than maintenance of low disease activity. The 'overarching principles' in the application of treatment for SpA, including PsA, include shared decision-making between the patient and rheumatologist, involvement of other specialists relevant to the extra-articular manifestations of SpA, such as dermatologists and gastroenterologists, and maintenance of quality of life for all patients.
Clearly, the evidence base to support the targets of treatment needs to be expanded, and future treatment of PsA will be dependent on acquisition of this evidence base. Interestingly, the recommendations listed above do not advocate the assessment of PsA patients at the earliest time point in the course of their disease, yet there is evidence to suggest that earlier presentation in the disease course is associated with better clinical and radiographic outcomes and the establishment of early arthritis clinics to accommodate early PsA could have a prognostic benefit on the course of PsA.
The TICOPA protocol study will provide important data in that regard. This study, inspired by the TICORA study in RA, is a UK-based, open-label, randomized controlled study examining clinical and radiographic outcome (ACR20, 50 and 70 response, PASI scores, change in enthesitis and dactylitis scores, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index and change in Sharp/van der Heijde scores) in those randomized to receive either standard care or intensive management in patients with early, treatment-naive PsA. The treatment target in those receiving intensive management will be minimal disease activity, as defined by Coates et al..
Treatment of psoriatic disease according to prespecified targets will be the basis of all future therapeutic regimens. The pursuit of disease control, however, will need to account for individual patient needs and the heterogeneity of the PsA population as a whole, including susceptibility to treatment toxicity and adverse events.
Treatment Strategies
There have been few studies comparing the efficacy of medication combinations in PsA, unlike, for example, the BeSt trial in RA. The BeSt study is a single-blind, multicenter randomized trial comparing four different treatment strategies in patients (n = 508) with early RA (<2 years disease duration) with a predefined treatment target of a DAS28 score ≤2.4, with clinical evaluation at 3-month intervals. This trial has accumulated prospective data over 7 years and has informed rheumatologists that early and aggressive disease control results in less radiographic damage and functional decline over time, even allowing for DMARD/TNFi discontinuation and drug-free remission.
Applying a similar treatment strategy to PsA would be of enormous interest to rheumatologists. Given the lower prevalence of PsA compared with RA; however, international collaboration would be required to attain adequate numbers to sufficiently power the study. In such an instance, GRAPPA may play a central role.
Trials are all on Polyarticular PsA: What About Other 'Forms'?
There are limited data regarding the use of DMARD and TNFi in the treatment of oligoarthritis, enthesitis and dactylitis; however, the initial clinical trials with TNFi showed that infliximab and golimumab have efficacy in treatment of enthesitis, dactylitis and psoriasis, while golimumab has also been shown to improve nail disease in psoriasis.
Treatment recommendations for predominantly axial disease in PsA, however, are based on observational studies in the PsA population and also extrapolated data from ankylosing spondylitis patients with psoriasis.
Future studies need to focus on all the musculoskeletal and cutaneous manifestations of psoriatic disease, with predefined criteria for disease activity in each domain, with applicable and validated outcome measures.
