Disease-modifying Antirheumatic Drugs In Psoriatic Arthritis Research Articles

Psoriatic Arthritis and Metabolic Syndrome: Is There a Role for Disease Modifying Anti-Rheumatic Drugs?

Although psoriatic arthritis (PsA) primarily leads to joint and skin damage, it is associated with higher prevalence of metabolic syndrome (MetS) and its components, namely hypertension, dyslipidemia, obesity, and type II diabetes. Additionally, chronic inflammation is known to aggravate these cardiometabolic factors, thus explaining the enhanced cardiovascular (CV) morbidity and mortality in RA. Furthermore, emerging evidence suggest that some risk factors can fuel inflammation, thus pointing to a bidirectional crosstalk between inflammation and cardiometabolic factors. Therefore, dampening inflammation by disease-modifying anti-rheumatic drugs (DMARDs) may be thought to ameliorate MetS burden and thus, CV risk and disease severity. In fact, recommendations for PsA management emphasize the need of considering comorbidities to guide the treatment decision process. However, the existing evidence on the impact of approved DMARDs in PsA on MetS and MetS components is far from being optimal, thus representing a major challenge for the clinical setting. Although a beneficial effect of some DMARDs such as methotrexate, TNF inhibitors and some small molecules is clear, no head-to-head studies are published and no evidence is available for other therapeutic approaches such as IL-23 or IL-17 inhibitors. This narrative review summarizes the main evidence related to the effect of DMARDs on MetS outcomes in PsA patients and identify the main limitations, research needs and future perspectives in this scenario.

Effectiveness of Conventional Disease-modifying Antirheumatic Drugs in Psoriatic Arthritis: A Systematic Review

BackgroundDue to the clinical heterogeneity of psoriatic arthritis (PsA), recommendations have been developed by international groups to guide therapeutic decisions of the rheumatologist. The objective of the current systematic review (RS) was to evaluate the evidence of efficacy of disease-modifying antirheumatic drugs (DMARDs) in PsA. MethodsLiterature search in Medline, EMBASE, Cochrane Library, from 2008 to 2014. We included RS, randomized clinical trials and observational studies, in patients with PsA and an evaluation of efficiency of conventional DMARDs (methotrexate, sulfasalazine, leflunomide), according to the following outcomes: peripheral and axial symptoms; peripheral radiological damage; enthesitis according to power Doppler ultrasound or magnetic resonance imaging (enthesitis count before and after therapy); dactylitis; uveitis. ResultsTitle and abstract were used to retrieve 1662 documents for this review (Medline, n=433; EMBASE n=1132; Cochrane, n=97), and 48 studies were selected for detailed reading; finally, 8 studies were included. ConclusionsSince the studies included are not robust, and there are arguments to support the effectiveness of methotrexate, the evidence observed with the treatment of DMARDs in PsA is not conclusive.

Real-life experience of using conventional disease-modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA). Retrospective analysis of the efficacy of methotrexate, sulfasalazine, and leflunomide in PsA in comparison to spondyloarthritides other than PsA and literature review of the use of conventional DMARDs in PsA.

With the aim of assessing the response to treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) used in patients with psoriatic arthritis (PsA), data on methotrexate, sulfasalazine (SSZ), and leflunomide were analyzed from baseline and subsequent follow-up (FU) questionnaires completed by patients with either PsA or other spondyloarthritides (SpAs). A single-center real-life retrospective analysis was performed by obtaining clinical data via questionnaires administered before and after treatment. The indices used were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), wellbeing (WB), and treatment effect (TxE). The indices measured at baseline were compared with those measured on one occasion in a FU visit at least 1 year later. A total of 73 patients, 51 with PsA (mean age 49.8±12.8 years; male-to-female ratio [M:F]=18:33) and 22 with other SpAs (mean age 50.6±16 years; M:F=2:20), were studied. BASDAI, BASFI, and WB displayed consistent improvements during FU assessments in both PsA patients and controls in comparison to baseline values. SSZ exhibited better efficacy as confirmed by TxE in both PsA patients and controls. ESR and CRP displayed no differences in either the PsA or the SpA group between the cases before and after treatment. Real-life retrospective analysis of three DMARDs used in PsA (and SpAs other than PsA) demonstrated that all three DMARDs that were used brought about improvements in BASDAI, BASFI, TxE, and WB. However, the greatest improvements at FU were seen with SSZ use in both PsA and control cohorts.

The Actual Role of Therapy with Traditional Disease-modifying Antirheumatic Drugs in Psoriatic Arthritis

Although several reviews and metaanalyses have shown lack of evidence of efficacy of traditional disease-modifying antirheumatic drugs (DMARD) in psoriatic arthritis (PsA), these drugs are very often used and are recommended by treatment guidelines around the world as first-line therapy for most patients with PsA. Some new investigations showed that higher doses of methotrexate (MTX) are more beneficial for patients with PsA with peripheral involvement. Also, observational studies have shown that retention of MTX for patients with PsA is comparable to that of patients with rheumatoid arthritis (RA), and that with MTX, remission is achievable by around 20% of patients with PsA. Sulfasalazine, leflunomide, and cyclosporine have also been shown to be effective in a small number of patients, although the overall effect on disease activity for these drugs is small. Although combination of anti-tumor necrosis factor agents with traditional DMARD is not mandatory in PsA as it is in RA, there is evidence that some extra benefit might be achieved when combinations are used, not only for the joints but for the skin. There is still room for the use of traditional DMARD in PsA, and for the time being, DMARD should still be considered as first-line therapy for most patients with PsA.

Update in treatment options for psoriatic arthritis

Psoriatic arthritis is a chronic inflammatory joint disease in patients with psoriasis and has a varying disease course. The majority of patients develop important disability and joint destruction within a few years of disease onset, necessitating the initation of disease-modifying therapy. Treatment options for peripheral disease, enthesitis and dactylitis include nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), local steroids and TNF-blocking agents. Axial disease is treated with NSAIDS and TNF blockade. Major clinical response is seen in approximately 30% of patients with methotrexate or leflunomide but no structural effect has yet been documented. Anti-TNF treatment has the best number-needed- to-treat/number-needed-to harm ratio of all DMARDs in psoriatic arthritis and is able to induce clinical remission in at least 30% of patients. TNF-blocking agents have also been demonstrated to slow down or halt radiographic progression.

Current and investigational treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is now recognised as a progressively destructive inflammatory arthritis that can lead to joint deformity and functional disability. Early diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) are necessary to control disease, particularly in patients with clinical factors and human leukocyte antigen markers predictive of progressive disease. However, there are few randomised controlled trials of the traditional DMARDs in PsA and none have demonstrated efficacy on axial manifestations or delay in radiological progression. The demonstration of raised levels of TNF-α in psoriatic skin and synovial tissue has provided a rationale for the application of biological agents in PsA. Furthermore, the recognition of the role of T-cell activation in both psoriasis and PsA has led to the therapeutic targeting of T lymphocytes, the results of which at this early stage are encouraging. This article reviews the studies of the most widely used traditional DMARDs in PsA followed by studies with leflunomide and the biological response modifiers, including TNF-α antagonists and T-cell-targeted therapies.