Current treatment landscape of psoriatic arthritis and future expectations
In western countries, psoriatic arthritis (PsA) is observed in about 20–30% of patients with psoriasis.1 In Hong Kong, the estimated prevalence rate of psoriasis is around 0.3%-0.6% and there was over 20,000 patients suffering from psoriasis as of 2015.2 However, higher variability is observed in the prevalence of PsA.1 While the population-based studies only capture patients with clinically relevant symptoms, psoriatic patients with mild arthritis are often unaware of their rheumatic disease.1 This is demonstrated by the high number of undiagnosed PsA patients who were discovered by the rheumatologists during medical consultations for psoriatic patients.1 Professor Tam, Lai-Shan, Head of the Division of Rheumatology, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, shared her insights on the current treatment landscape of PsA and future expectations.
Psoriatic arthritis: A complex disease
PsA is a heterogenous disease with chronic, inflammatory and musculoskeletal impacts associated with psoriasis. The most common type of psoriasis associated with PsA is psoriasis vulgaris or plaque psoriasis.3 Musculoskeletal manifestations of PsA include peripheral arthritis, spondylitis, dactylitis (inflammation of the whole digit), and enthesitis (inflammation where a tendon, ligament or joint capsule inserts onto the bone).3 Additionally, patients with PsA experience fatigue, physical function limitations, sleep disturbance, diminished work capacity, and social participation.3
PsA is associated with a variety of comorbidities such as cardiovascular disease, metabolic syndrome, obesity, diabetes mellitus, dyslipidemia, inflammatory bowel disease, fatty liver disease, uveitis, kidney disease, infections, osteoporosis, depression, central sensitization syndrome, and gout.4 These comorbidities affect both the clinical outcome and management of PsA patients, and thus it is important to identify and monitor comorbidities early.4 Moreover, a substantial prevalence of depression and anxiety has been observed among patients with PsA.5
Optimal disease assessment is the key to better clinical outcomes
The diagnosis of PsA is primarily based on clinical and imaging features.6 Patients are assessed on five domains: Psoriasis, peripheral joint disease, axial disease, enthesitis, and dactylitis, although combinations of domains may be present in an individual patient.6 The most important measurement of peripheral arthritis is tender and swollen joint counts, with a combination of patient reported outcomes (PROs).7 In order to assess the joints affected in PsA, 68/66 joint count and disease activity score (DAS 28) are recommended.7 Additionally, the American College of Rheumatology (ACR) criteria is used to assess the disease, and 20%, 50% and 70% reductions in tender and swollen joint counts are used to evaluate the success of treatments.7
The Disease Activity Index for Psoriatic Arthritis (DAPSA) was the first validated measurement tool specifically designed for the clinical assessment of PsA and developed based on a clinical cohort of PsA patients.7 It composed of a 68/66 joint count, a patient global assessment, a patient assessment of pain, and C-reactive protein measurement to provide a composite clinical outcome measure.7 “The DAPSA scores, responses and thresholds make it a potentially useful tool in a clinical setting, to track response in arthritis to interventions,” stated Prof. Tam, and she pointed out “It is compulsory to assess optimal disease levels and utilize extensive measurement tools for better diagnosis and clinical outcome.” She also stated that the minimum disease activity (MDA) has been used for the assessment of disease levels in clinical trials. In the MDA criteria, seven different items are assessed individually: Tender joint count, swollen joint count, enthesitis count, psoriasis area severity index (PASI) or body surface area, patient global visual analogue scale, patient pain on the visual analogue scale, and Health Assessment Questionnaire-Disability Index (HAQ-DI).7
Advanced treatment options and new guidelines in PsA
A diverse array of therapeutic options are currently available for the treatment of PsA patients.8 Adjunctive therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose corticosteroids, injectable forms of corticosteroids, and conventional disease-modifying antirheumatic drugs (DMARDs), including methotrexate (MTX), leflunomide, sulfasalazine, and cyclosporine have been used for decades.8 Patients with an inadequate response to NSAIDs or conventional DMARDs, or patients who are naïve to such treatments can consider biologic DMARDs (bDMARDs), which include tumor necrosis factor (TNF) inhibitors, interleukin-17 (IL-17) inhibitors, IL-12/23 and IL-23 inhibitors.8 Prof. Tam mentioned that patients who exhibit persistent resistance to bDMARDs or show signs of toxicity may be considered for oral targeted synthetic DMARDs (tsDMARDs) such as phosphodiesterase 4 inhibitors or JAK inhibitors. Most importantly, patient comorbidities should be taken into account when choosing medications. However, Prof. Tam emphasized that the cost of the bDMARDs and tsDMARDs is one of the unmet needs in the treatment landscape. Fortunately, some of these drugs, including JAK inhibitors, are supported by the Samaritan Fund in Hong Kong. “We discuss the treatment strategies with the patients, giving details of safety, efficacy and cost. That helps the patient make an informed decision,” added Prof. Tam.
In the last 5 years, there has been a rapid expansion of pharmacological agents available for the treatment of PsA, particularly with the introduction of targeted therapies.8 A number of PsA treatment guidelines have been developed, for instance ACR and National Psoriasis Foundation (NPF) in 2018, European League Against Rheumatism (EULAR) in 2015, and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in 2015.3 Figure 1 illustrates the guidelines published by the GRAPPA.9 Prof. Tam highlighted, “In Hong Kong, we follow the Hospital Authority guidelines based on GRAPPA and EULAR, but it is also important to manage patients according to their individual assessments.”
Treating to target enhances the clinical outcome on PsA
A treat-to-target (T2T) approach for PsA was first introduced in 2015 by EULAR.10 In T2T, treatment is adjusted to reach a pre-determined treatment goal, such as low disease level or disease remission.11 The frequency of monitoring is determined by the disease activity and patient’s overall health.11 Most importantly, it was demonstrated that T2T with a tight control strategy can significantly improve the clinical outcome as reflected by the ACR20, with the greatest benefits seen in more stringent outcome measures, such as ACR70 and 75% improvement in psoriasis area severity index (PASI75).12 According to the international T2T taskforce, DAPSA remission/low disease activity with MDA is the treatment target in PsA clinical trials.7
Oral versus subcutaneous drug delivery in PsA
The introduction of targeted synthetic DMARDs, the first and only oral treatments, is leading positive outcomes in the treatment landscape of PsA.13 Various clinical trials have shown efficacy of the JAK inhibitors in PsA.14,15 OPAL Broaden is a randomized, placebo-controlled and double-blind phase 3 trial evaluating the efficacy and safety of tofacitinib, the oral JAK inhibitor, over the TNF inhibitor adalimumab, in PsA patients who previously had an inadequate response to at least one csDMARD.14 The efficacy of the oral JAK inhibitor was superior to that of placebo at month 3 and clinically meaningful improvements were observed in PROs.14,15
Also in patients with active PsA who had an inadequate response to TNF inhibitors, oral JAK inhibitor compared to placebo was more effective in reducing disease activity.16 A comparison of the oral JAK inhibitor and the subcutaneous biologic DMARD is presented in the Table 1.14 However, Prof. Tam commented, “Long term efficacy and safety data in JAK inhibitors are essential considerations for the clinical decision making.” She further noted that the decision to choose oral JAK inhibitors depends on her discussion with the patient regarding treatment efficacy, safety, cost, and preference of the route of administration. The oral administration of tofacitinib could provide ease and convenience to PsA patients, and thus improve their quality of life (QoL). Prof. Tam also commented, “According to various clinical trials, oral JAK inhibitors have contributed to the improved QoL of PsA patients.”
Treatment landscape of PsA in next 10 years
Prof. Tam expects that there will be more biosimilar drugs available and at a lower cost for the PsA treatment in next 10 years. Subsequently, more patients can be treated according to the T2T principle. With the advanced research in immunology, more effective and safer drugs would emerge in the field, and the long-term efficacy data of JAK inhibitors in treating PsA would be available. Prof. Tam stated, “I hope patients could be identified and treated early to prevent joint damage and improve their QoL” and she says, “Hopefully, we would be able to prevent the disease altogether.” In order to achieve that goal, Prof. Tam proposes a competent referral strategy for the early identification of PsA among dermatologists and rheumatologists for patients suffering from psoriasis.
Message to the dermatologists and rheumatologists
Although new drugs have been approved for the treatment of PsA, treatment decisions should be made according to available safety and efficacy data. Rheumatologists should be aware that the treatment to target is feasible and has been proven to be effective, not only by ameliorating the symptoms, but also improving the QoL. Prof. Tam further explained, “By treating to a target, we expect to lower the long-term comorbidities, including cardiovascular outcome.” Prof. Tam also said that vigilant use of clinical assessments like MDA could help achieve the T2T. “Close collaboration of dermatologists and rheumatologists can pave the way for establishing a smoother referral system to identify PsA patients and initiate treatments earlier,” concluded Prof. Tam.
PsA is a chronic inflammatory disease that presents with skin lesions, peripheral or axial arthritis, dactylitis, or nail lesions. As PsA normally occurs after the development of psoriasis, patients should be screened and identified early in order to receive treatment on time. With the availability of multiple disease assessment tools and advanced pharmacological therapies, the treatment of PsA should prioritize the reduction of joint damage. In addition, with the development of T2T approach, PsA patients can experience fewer comorbidities as well as improved QoL and function.
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