In August 2007, NICE issued technology appraisal 125 on Adalimumab for the treatment of psoriatic arthritis.1 This is in addition to its previously issued guidance on the use of etanercept and infliximab for psoriatic arthritis (PsA).2 A review of these three agents is scheduled for August 2008.
What is psoriatic arthritis?
Psoriatic arthritis is an inflammatory condition that coincides with the presence of the skin rash psoriasis, and is equally distributed between males and females.3 Psoriasis occurs in 1–3% of the population, with approximately one-third of patients subsequently exhibiting signs of PsA.4 Approximately 40–60% of patients with PsA (at hospital clinics) have erosive and deforming arthritis, which is progressive from the first year of diagnosis.5,6
Effects of psoriatic arthritis
Chronic joint damage can result from PsA in much the same way as with rheumatoid arthritis (RA), subsequently leading to increased disability7,8 and mortality.9,10 The social and financial implications of these effects are also important in terms of personal loss, and both direct and indirect costs to the country (e.g. costs relating to medical care and inability to work, etc).
Psoriasis can be associated with an increase in non-melanoma skin cancers when it is treated with UV light in the form of PUVA (pulsed ultraviolet A)and particularly in those patients who have also been treated with ciclosporin.11,12
Moll and Wright criteria
The original diagnostic criteria for PsA by Moll and Wright are the simplest and the most frequently used in current studies. These are:13
- an inflammatory arthritis (peripheral arthritis and/or sacroiliitis or spondylitis)
- the presence of psoriasis
- the (usual) absence of serological tests for rheumatoid factor.
Moll and Wright went on to describe five subgroups of PsA based on these diagnostic criteria:13
- distal interphalangeal joint only
- asymmetrical oligoarthritis
- arthritis mutilans.
The Moll and Wright criteria suggested that subsets of PsA were separate disease entities. Oligoarthritis, for example, is usually not debilitating and, by definition, affects a small number of joints at one time. Arthritis mutilans, however, is a rapidly progressive arthritis, causing extensive damage to the joints of the hands and feet, along with characteristic deformities. However, in contrast to the categorisation by Moll and Wright, considerable overlap between the subgroups is now recognised.14
Features of psoriatic arthritis
Psoriatic arthritis has certain characteristic features. These are:
- spinal involvement—reported in up to 51% of patients with PsA15
- enthesitis—inflammation at the sites of tendon, ligament, and joint capsule insertion into bone16
- dactylitis—swelling of a whole digit resulting from a combination of synovitis and inflammation of tendon and ligament insertions.16
Although it was previously thought to be a benign condition, PsA is now recognised as a potentially destructive erosive arthropathy.5
Relief of symptoms such as joint, tendon, and entheseal inflammation has been the traditional aim of standard therapy, comprising prompt intervention with non-steroidal anti-inflammatory drugs (NSAIDs) and injection of corticosteroids. Disease-modifying anti-rheumatic drugs (DMARDs) are used as second-line agents in more severe cases. However, NSAIDs and corticosteroid injections are still an important part of therapy, although most long-term studies of PsA have demonstrated steady progress of the disease in spite of the use of such medication. Current practice aims for early diagnosis of the condition and commencement of DMARDs—sulfasalazine or methotrexate are widely used in clinical practice.
Results of a Cochrane systematic review concluded that only sulfasalazine and high-dose parenteral methotrexate had been documented as being effective for treatment of PsA17 (the latter at a dose considered too toxic by today’s standards). Methotrexate is currently being further evaluated in a multicentre UK randomised controlled trial. Patients whose clinical response is poor can be switched to an alternative DMARD or started on combination therapy with more than one DMARD.
Patients are classed as failing to respond to therapy if they still have active disease and have had adequate therapeutic trials of at least two of the standard DMARDs individually or in combination.14
The key role that tumour necrosis factor (TNF)-?, a proinflammatory cytokine, plays in inflammation of skin and synovium has recently been a focus of interest,18 and it is a logical target for treatment in RA. Early studies and trials have shown that TNF-? blockade is an effective treatment for PsA.19
The British Society for Rheumatology produced a guideline in 2005 for the management of PsA by treatment with anti-TNF-?.14 This guideline recommends the use of anti-TNF-? agents when two DMARDs have failed to manage PsA.
In addition to etanercept and infliximab, which NICE reviewed in 2006,2 adalimumab has now been recommended by the organisation for use in anti-TNF-? therapy.1 Etanercept is a recombinant human TNF receptor:Fc fusion protein, administered subcutaneously twice weekly at a dose of 25 mg. The chimeric monoclonal antibody infliximab has a more complex method of administration, with a dose of 5 mg/kg given by intravenous infusion over 2 hours at weeks 0, 2, and 6, and every 8 weeks after that. Adalimumab is a recombinant human monoclonal antibody that binds specifically to TNF-?, and blocks interaction with its cell-surface receptors and limits the promotion of inflammatory pathways. The recommended dose of adalimumab is 40 mg every other week, delivered subcutaneously.
Recommendations in the NICE technology appraisal
NICE technology appraisal 125 looked at prescription of adalimumab for the treatment of PsA.1 It considered the efficacy and health economics of the widespread use of etanercept and infliximab, and made recommendations based on the findings. NICE has recommended the following:1
- within its licensed indication, adalimumab is an option for the treatment of adults with active and progressive PsA only when the following criteria are met
- when the patient has peripheral arthritis with three or more tender joints and three or more swollen joints
- adequate trials of at least two standard DMARDs, administered either singly or in combination, have wrought no improvement in the PsA
- treatment with adalimumab should be discontinued after 12 weeks in adults when their PsA has not shown an adequate response when assessed using the PsA response criteria
- specialists with experience in diagnosing and treating PsA should be responsible for initiating and supervising treatment of PsA with adalimumab.
Implications for GPs
Before the guidance was issued, rheumatologists were only able to prescribe adalimumab subject to financial approval by their local primary care trust (PCT) and strategic health authority. It is difficult for any PCT to justify prescription of any drug that has not received NICE approval, therefore most requests for adalimumab for use in PsA were refused. The decision by NICE to recommend its use after consideration of the health-economic implications should mean that rheumatologists are more likely to receive financial approval for starting therapy with this drug.
Patients with PsA will, therefore, be able to receive effective treatment for their condition, as is the case for patients with RA. Anti-TNF-? treatment has revolutionised the treatment of RA and should now do the same for PsA. For those patients who did not respond to traditional DMARDs, they are now offered the chance of a dramatic new treatment option.
However, GPs should bear in mind the increased susceptibility to infections of patients who are on anti-TNF-? therapy,4 and the increased risk of patients with psoriasis developing melanoma.11,12 They should follow the guidance issued by their local rheumatology department.
- National Institute for Health and Care Excellence. Adalimumab for the treatment of psoriatic arthritis. Technology appraisal 125. London: NICE, 2007.
- National Institute for Health and Care Excellence. Etanercept and infliximab for the treatment of adults with psoriatic arthritis. Technology appraisal 104. London: NICE, 2006.
- Shbeeb M, Uramoto K, Gibson L et al. The epidemiology of psoriatic arthritis in Olmsted County, Minnesota, USA, 1982–1991. J Rheumatol 2000; 27 (5): 1247–1250.
- Gladman D. Psoriatic arthritis. Baillière’s Clin Rheumatol 1995; 9 (2): 319–329.
- Gladman D, Stafford-Brady F, Chang C et al. Longitudinal study of clinical and radiological progression in psoriatic arthritis. J Rheumatol 1990; 17 (6): 809–812.
- McHugh N, Balakrishnan C, Jones S. Progression of peripheral joint disease in psoriatic arthritis: a 5-yr prospective study. Rheumatology 2003; 42 (6): 778–783.
- Sokoll K, Helliwell P. Comparison of disability and quality of life in rheumatoid and psoriatic arthritis. J Rheumatol 2001; 28 (8): 1842–1846.
- Husted J, Gladman D, Farewell V, Cook R. Health-related quality of life of patients with psoriatic arthritis: a comparison with patients with rheumatoid arthritis. Arthritis Rheum 2001; 45 (2): 151–158.
- Wong K, Gladman D, Husted J. Mortality studies in psoriatic arthritis: results from a single outpatient clinic. I. Causes and risk of death. Arthritis Rheum 1997; 40 (10): 1868–1872.
- Gladman D, Farewell V, Wong K, Husted J. Mortality studies in psoriatic arthritis: results from a single outpatient center. II. Prognostic indicators for death. Arthritis Rheum 1998; 41 (6): 1103–1110.
- Paul C, Ho V, McGeown C et al. Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study. J Invest Dermatol 2003; 120 (2): 211–216.
- Stern R, Lunder E. Risk of squamous cell carcinoma and methoxsalen (psoralen) and UV-A radiation (PUVA). A meta-analysis. Arch Dermatol 1998; 134 (12): 1582–1585.
- Moll J, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973; 3 (1): 55–78.
- Kyle S, Chandler D, Griffiths C et al; British Society for Rheumatology Standards Guidelines Audit Working Group (SGAWG). Guideline for anti-TNF-alpha therapy in psoriatic arthritis. Rheumatology (Oxford) 2005; 44 (3): 390–397.
- Gladman D, Brubacher B, Buskila D et al. Psoriatic spondyloarthropathy in men and women: a clinical, radiographic, and HLA study. Clin Invest Med 1992; 15 (4): 371–375.
- Mease P, Antoni C, Gladman D, Taylor W. Psoriatic arthritis assessment tools in clinical trials. Ann Rheum Dis 2005; 64 (Suppl 2: ii): 49–54.
- Jones G, Crotty M, Brooks P. Interventions for psoriatic arthritis. Cochrane Database Syst Rev 2000; (3): CD000212.
- Ritchlin C, Haas-Smith S, Hicks D et al. Patterns of cytokine production in psoriatic synovium. J Rheumatol 1998; 25 (8): 1544–1552.
- Mease P, Goffe S, Metz J et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000; 356 (9227): 385–390.G