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Therapeutics


NSAIDs and, despite the importance of this topic and data supporting the increased risk of CV events in these patients, no studies addressing the CV toxicity of NSAIDs in PsA were identified.4


Synthetic DMARDs Methotrexate


The recent introduction of new biological molecules (biologic DMARDs) for the treatment of PsA has stimulated the review of evidence for the efficacy of synthetic DMARDs. In daily clinical practice MTX is widely used, but the evidence for the efficacy or effectiveness of this molecule on the broad spectrum of the disease (skin, nail, peripheral joint, axial, enthesitis, dactylitis) is poor, graded as level B of evidence for polyarticular disease.5 However a cross-sectional study using the database from the ClASsification criteria for the diagnosis of Psoriatic ARthritis (CASPAR) study showed that MTX, among the DMARDs, was the most used medication (39% of the total population, n=433) in real life.6


the treatment of PsA patients either as monotherapy or in combination with other DMARDs.


As a monotherapy, a study recently evaluated the long-term use of MTX in PsA patients with peripheral joint involvement in an everyday clinical practice setting.7


MTX has been used for


baseline abnormalities in a standard laboratory test was assessed in three different groups of early arthritis and the results obtained showed that these abnormalities are quite frequent but did not affect the treatment with MTX.9 Finally, MTX therapy has been associated with hepatic, pulmonary, bone marrow toxicity and teratogenicity.10


Therefore, This study showed that,


out of 174 patients, 104 (59.8%) were still taking MTX after three years of treatment. Adverse events were observed, for example, raised transaminase levels, nausea and sickness, which led to the treatment being withdrawn. The authors specified that no liver biopsy was performed to assess any liver damage and that all side effects were reversible when MTX was suspended.7


In contrast with these results, obtained from actual clinical practice, a randomised controlled trial (RCT) on MTX in PsA patients has been published.8


the potential side effects of MTX, namely elevation of transaminase, could limit its use in patients with psoriasis and a history of alcohol misuse and other disorders, such as obesity (fatty liver). However, even if MTX has some potential side effects and contraindications, there is some evidence that remission can be achieved with this medication in approximately 25% of PsA patients and a condition of drug-free remission is possible in 10% of patients.11


In particular,


the study was designed as a double-blind RCT comparing MTX (15mg/weekly) with placebo in active PsA; this was the first large RCT in PsA. In terms of side effects, no differences were observed between the two arms of the study and MTX was discontinued in nine patients due to common adverse events seen in less than 5% of the MTX arm, with some episodes of nausea, respiratory tract infections, abdominal pain and liver function test abnormalities.8


In terms of contraindications for treatment with MTX, the impact of


Sulphasalazine SSZ has often been the first DMARD used for the treatment of PsA. SSZ was compared with placebo in six studies; however, the efficacy of SSZ was recorded in these studies in peripheral arthritis only, with a lack of efficacy on the axial component of the disease.12


In particular, up to a third of


patients enrolled for these studies showed some adverse effects of the treatment, namely gastrointestinal intolerance, dizziness and raised liver function tests.


Cyclosporin A


CsA is an immunosuppressive agent that has the capacity to inhibit the activity of transcription factors of the nuclear factor of activated T cell family, acting in stimulated T cells by suppressing interleukin 2 (IL-2) production and IL-2 receptor expression. CsA was effective for the treatment of


psoriasis and its use for skin treatment can be summarised as follows: (a) intermittent course, usually short periods of time


(b) continuous treatment (c) crisis intervention (d) combination of sequential and rotational therapy.


There are three main studies on the use of CsA for PsA in the literature that compared the efficacy and safety of CsA with other DMARDs. Spadaro et al13 compared CsA with MTX in a small group of PsA patients. In 2005, Fraser et al14 carried out a study on combination therapy (CsA + MTX) versus MTX. In 2001, an Italian multicentre study was carried out to compare the efficacy and safety of CsA with a symptomatic therapy alone or in combination with SSZ.15 Recently, CsA showed a synergistic effect with etanercept in reaching a good disease control in a group of PsA patients.16 CsA was approved in the US by the US Food and Drug Administration (FDA) for severe, recalcitrant psoriasis, as well as for PsA. CsA has been associated with nephrotoxicity and hypertension and it is recommended for only a short period of time (12 months). Therefore, high blood pressure and kidney failure (even mild) are the main two contraindications to consider when evaluating any possible treatment with CsA.10


Leflunomide


Leflunomide is a selective pyrimidine synthesis inhibitor with the capacity to inhibit T-cell activation and proliferation. It showed efficacy in improving the articular involvement of, as well as disability and skin psoriasis, in 190 PsA patients.17


In terms of side effects, the www.hospitalpharmacyeurope.com


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