Current therapy options

The heterogeneity of psoriatic arthritis (PsA) suggests a high number of undiagnosed manifestations. Guidance is provided by the CASPAR classification criteria. Therapy concepts should be multimodal – supported by a broad spectrum of drugs, which is systematized here.

Psoriatic arthritis (PsA) is an inflammatory rheumatic disease that affects men and women in equal proportions (1:1) and shows heterogeneous courses [1]. PsA used to be considered the “stepsister” of rheumatoid arthritis (RA), but now the pathogenesis and the proinflammatory cytokines involved (tumor necrosis factor-α (TNF-α), interleukin (IL)-12/23, interleukin (IL)-17, phosphodiesterase (PDE)-4) suggest a closer association with both seronegative spondyloarthritides and autoinflammatory syndromes [1].

Data from previous epidemiological studies suggested that PsA manifests in 7-20% of patients with psoriasis vulgaris (PsO) [2]. Recent data suggest a higher prevalence of joint infection (approximately 30%) and emphasize that there is a high incidence of undiagnosed manifestations due to the heterogeneity of the disease [2]. Accordingly, good interdisciplinary collaboration between dermatologists and rheumatologists is critical. Appropriate screening procedures, e.g. by means of standardized questionnaires and joint consultations, are important to ensure early diagnosis and initiation of therapy.

PsA phenotypes

Moll and Wright have described five subtypes of PsA depending on their dominant manifestation [3]. They distinguished a symmetric course resembling RA from oligoarticular forms occurring asymmetrically with or without axial involvement. There are also mono- or oligoarticular courses that resemble arthritis urica with involvement of the big toe or large joints (knee, OSG), as well as osteoarthritis-like forms that affect the distal interphalangeal (DIP) joints in particular.

Guidance for the diagnosis of PsA is provided by the CASPAR classification criteria (Table 1) and, for peripheral spondyloarthritis, the ASAS classification criteria (Table 2), which are designed primarily for clinical trials.

Decisive for the therapy of PsA is, in addition to the extent and form of psoriasis, the joint involvement pattern ( axial, peripheral) as well as the enthesitis ( Fig. 1) and dactylitis (Fig. 2) typically occurring in PsA, and possibly also other extra-articular manifestations such as uveitis.

Current therapeutic options for the different PsA forms

The therapy of psoriatic arthritis is based on the current guidelines of the European League Against Rheumatism [4] (EULAR) and on the guidelines of the joint expert group for PsO and PsA: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The goal of therapy should be clinical and laboratory remission of the disease within three to six months, although activity scores are often more difficult to apply to PsA than to RA [6].

In principle, the leading symptomatology is decisive for the choice of therapeutic agent. Mild courses with intermittent arthralgias and/or arthritides affecting only a few joints can be successfully treated with NSAIDs and additional intraarticular glucocorticoid injections [4,5]. Local glucocorticoid infiltration may also be tried initially for periarticular inflammation of the finger or toe joints (dactylitis). In cases of persistent oligo- or polyarthritis and/or dactylitis, as well as in cases of unfavorable prognostic factors, especially already radiologically detectable structural changes, conventional basic therapeutics (cDMARDs, e.g. MTX, leflunomide, salazopyrin) are the therapy of choice [4]. Unfortunately, the level of evidence for therapy with cDMARDs is based on sparse data and lacks large randomized controlled trials demonstrating the benefits of cDMARDs.

If the skin and joints are affected, methotrexate (MTX) is usually used as the initial therapeutic agent at a dose of 15 mg/week s.c. [4,5]. This is based on good clinical experience and a high adherence rate. Under adequate folic acid substitution and with good tolerability, a dose increase up to 25 mg/week is possible, depending on the activity of peripheral arthritis and the extent of psoriasis [4,5].

One study showed that 22% of patients on MTX achieved low disease activity after three months [7], while an earlier study did not demonstrate a clear effect on peripheral arthritis [8]. Axial involvement is unlikely to be affected by MTX. If peripheral joint involvement dominates and MTX intolerance is present, leflunomide or sulfasalazine can be used as alternatives, but unlike MTX, these have little effect on skin involvement [4,5].

In cDMARD failure, efficacy for both PsO and PsA has been demonstrated for all of the five approved TNF-α blockers: Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab. Etanercept shows a lower or delayed response regarding PsO compared to the other [4,5]. In addition, TNF-α inhibitors are recommended as initial therapeutic agents by EULAR for NSAID-refractory enthesitis and axial involvement [4], as cDMARDs lack efficacy on these phenotypes of PsA and the available safety data from international registries are more extensive than those on the new classes of agents.

New targets in PsA

A special place is given to the targeted synthetic (ts) DMARD apremilast, a PDE-4 inhibitor, which is used after failure of MTX in moderate disease activity and especially in contraindications to biologic therapy (comorbidities, risk of infection) [9]. In the current studies, a moderate effect on skin, joint infection, and enthesitis was demonstrated with a good safety profile and peroral administration [9]. Thus, apremilast can be classified as an effective basic therapy after cDMARDs and before biologics.

Finally, IL-12/23 and IL-17 blockade are critical and potent targets for inhibiting the inflammatory activity of PsA, especially when it comes to enthesitis as well as, for IL-17, additionally axial involvement.

The IL-12/23 inhibitor ustekinumab is well efficacious in both cutaneous psoriasis and active PsA unresponsive to cDMARDs [10]. A recent analysis even showed superiority of ustekinumab over adalimumab in the treatment of enthesitis [11].

The IL-17 inhibitor secukinumab additionally has a good effect on axial involvement in PsA and can alternatively be initiated in TNF-α blocker failure to change the mode of action [12]. According to GRAPPA recommendations, unlike in the EULAR recommendations, these drugs can be used equivalently to TNF-α blockers in an active form of PsA after cDMARD failure and in enthesitis refractory to local measures and NSAIDs [5]. In clinical practice, they are more often considered as second-line biologics when treatment with TNF-α blockers has failed and a change in the mode of action promises success.

Concluding remarks

We now have access to a wide range of drugs for the treatment of PsA and can optimize clinical and patient-defined outcomes (quality of life, pain, fatigue [Fatigue]) through the targeted use of these substances.

In PsA, a multimodal therapeutic approach is required to identify potential comorbidities (metabolic syndrome, cardiovascular disease, depression) early and to improve long-term outcome (work capacity, mortality).

Other important pillars of therapy to maintain and improve joint function include regular physical therapy and occupational therapy treatments, as well as instruction on joint protection and patient education, which helps to educate patients about their condition as well as their self-responsibility.
Finally, a crucial part of a comprehensive therapy concept is the interdisciplinary exchange between the treating dermatologists and rheumatologists.

Take-Home Messages

Early diagnosis and treatment of psoriatic arthritis (PsA) is critical for clinical and functional outcome.
The therapy of PsA depends on the respective manifestation form and disease activity.
TNF-α blockers remain highly valued in the treatment of active forms of PsA.
New promising targets in PsA therapy are IL-12/23, IL-17 and PDE-4.

Literature:

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