600 patients and some open- and case-control studies. The general impression is that SSZ has a positive but modest effect on skin, peripheral and axial manifestations of PsA.12,13
In a 24-week small trial assessing CsA monotherapy (3mg/kg/day) versus symptomatic treatment, CsA appeared effective for the treatment of peripheral arthritis and axial involvement. In a 12-month RCT, 72 patients with active PsA and an incomplete response to MTX were randomised to either CsA or placebo in addition to MTX. The only significant differences between the groups were in synovitis detected by ultrasound and PASI score in favour of the combined arm. There was no direct evidence that CsA reduces the progression of radiographic damage.12
Who should be treated with DMARD? According to the European League Against Rheumatism (EULAR) Recommendations for PsA Management, patients with active disease and potential poor prognosis should be started on DMARD. Active disease is defined globally as one or more tender and inflamed joint and/or tender enthesis point and/or dactylitic digit and/or inflammatory back pain; however, for the introduction of synthetic DMARD therapy, only joint involvement is taken into account. Poor prognosis refers to the number of actively inflamed joints (five or more), elevated acute phase reactants, radiographic damage that is progressing, previous use of GCs, loss of function and diminished quality of life.10
Due to their
best benefit to risk ratio, MTX and LEF are the preferred DMARDs for treating PsA.19
New systemic oral drugs Apremilast
Apremilast is a new oral small molecule, which specifically inhibits the activity of PDE4, an isoform found predominantly in immune cells. PDE4 inhibition elevates intracellular cAMP, which can downregulate the inflammatory responses through mechanisms such as partially inhibiting expression of inflammatory cytokines and increasing expression of anti-inflammatory mediators such as interleukin-10.8,20
The Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) programme is assessing the effects of apremilast on the signs and symptoms of PsA in four randomised, placebo-
controlled trials with long-term, open- label extensions. Results from the first trial (PALACE 1), which randomised more than 500 patients with active PsA despite prior DMARDs and/or biologics, have recently been published. At week 16, significantly more patients receiving apremilast 20mg BID (31.3%) and 30mg BID (39.8%) achieved an ACR20 response versus placebo (19.4%). Biologic-naïve patients generally experienced higher absolute ACR20 response rates compared with biologic- experienced patients and patients with a history of biologic failure. In general, a dose-related effect was observed with higher ACR20 response rates achieved in those receiving apremilast 30mg BID versus 20mg BID. Greater improvements in major secondary measures (physical function, tender/swelling joint counts, enthesitis, dactylitis, psoriasis) were evident with both apremilast doses versus placebo. Both doses were generally well tolerated over 24 weeks. The most common adverse events were largely gastrointestinal (diarrhoea and nausea) and did not lead to discontinuation.20 These results suggest that apremilast may become an important addition to the current PsA treatment armamentarium.
The JAK family of receptor-associated tyrosine kinases serve as intracellular signal transduction molecules linked to surface receptors for multiple pro- inflammatory cytokines, which are crucial for T cell activation and functioning. Tofacitinib is an oral small-molecule inhibitor of JAK1, JAK3 and, to a lesser extent, JAK2. There are promising results with tofacitinib in psoriasis but no clinical efficacy and safety data for PsA are yet available.7,13 l
References 1. Nestle FO et al. Psoriasis. N Engl J Med 2009;361(5):496–509.
2. Gladman DD et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005;64(Suppl. 2):ii14–7.
3. Mease PJ et al. Prevalence of rheumatologist- diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol 2013;69(5):729–35.
4. Taylor W et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006;54:2665–73.
5. Boehncke WH, Boehncke S. Cardiovascular
mortality in psoriasis and psoriatic arthritis: epidemiology, pathomechanisms, therapeutic implications, and perspectives. Curr Rheumatol Rep 2012;14:343–8.
6. Queiro R et al. Age at disease onset: a key factor for understanding psoriatic disease. Rheumatology (Oxford) 2014;53:1178–85.
7. Furumoto Y, Gadina M. The arrival of JAK inhibitors: advancing the treatment of immune and hematologic disorders. BioDrugs 2013;27:431–8.
8. Serezani CH et al. Cyclic AMP: master regulator of innate immune cell function. Am J Respir Cell Mol Biol 2008;39:127–32.
9. Ritchlin CT et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis 2009;68:1387–94.
10. Gossec L et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis 2012;71:4–12.
11. Smolen JS et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis 2014;73:6–16.
12. Ash Z et al. A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis 2012;71:319–26.
13. Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs 2014;74:423–441.
14. Kingsley GH et al. A randomized placebo- controlled trial of methotrexate in psoriatic arthritis. Rheumatology (Oxford) 2012;51:1368–77.
15. Baranauskaite A et al. Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate- naive patients: the RESPOND study. Ann Rheum Dis 2012;71:541–8.
16. Ceponis A, Kavanaugh A. Use of methotrexate in patients with psoriatic arthritis. Clin Exp Rheumatol 2010;28(5 Suppl. 61):S132–7.
17. Chandran V, Schentag CT, Gladman DD. Reappraisal of the effectiveness of methotrexate in psoriatic arthritis: results from a longitudinal observational cohort. J Rheumatol 2008;35:469–71.
18. Behrens F et al. Leflunomide in psoriatic arthritis: results from a large European prospective observational study. Arthritis Care Res 2013;65:464–70.
19. Fernández Sueiro JL et al. Consensus statement of the Spanish Society of Rheumatology on the management of biologic therapies in psoriatic arthritis. Reumatol Clin 2011;7:179–88.
20. Kavanaugh A et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis 2014;73:1020–6.
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