Therapies for Axial Disease in Psoriatic Arthritis. A Systematic Review
PETER NASH
ABSTRACT.
Prevalence rates for axial involvement in psoriatic arthritis (PsA) vary from 40% to 74% depending upon criteria for diagnosis. In the absence of trial evidence to assess axial involvement in PsA, the GRAPPA group, by consensus, has suggested that outcome measures and therapies for axial disease in ankylosing spondylitis (AS) be used. This systematic review addresses the management of axial disease in PsA, and provides treatment recommendations based on the AS literature. (First Release May 15 2006; J Rheumatol 2006;33:1431–4)
Key Indexing Terms:
ANKYLOSING SPONDYLITIS
PSORIATIC ARTHRITIS
AXIAL DISEASE
SPONDYLOARTHROPATHY
PSORIASIS
ANTIRHEUMATIC THERAPY
PSORIATIC ARTHRITIS
AXIAL DISEASE
SPONDYLOARTHROPATHY
PSORIASIS
ANTIRHEUMATIC THERAPY
From the Department of Medicine, University of Queensland, Cotton Tree, Australia.
P. Nash, MBBS (Hons), FRACP.
Address reprint requests to Dr. P. Nash, Department of Medicine, University of Queensland, PO Box 59, Cotton Tree, Australia. E-mail: pnash@tpg.com.au
INTRODUCTION
Axial disease in psoriatic arthritis (axPsA) is common; prevalence rates range from 40% of PsA patients if inflammatory spinal pain is used as the diagnostic criteria, to 78% if radiologically defined sacroiliitis is required1. Despite shared features between axial disease in PsA and ankylosing spondylitis (AS), important distinctions have been described:
• Reduced male preponderance
• Less overall disease severity
• Less severe sacroiliitis
• Less syndesmophyte development (e.g., "spotty" asymmetric distribution of marginal and paramarginal syndesmophytes with random progression)
• Less cervical involvement
• Better preservation of spinal mobility
• Relative absence of ligamentous ossification
• Relative sparing of apophyseal joints
• Reduced association with HLA-B27 positivity
(prevalence rates from 21% to 76% with a strong association when positive with sacroiliitis)2-4
These observations, however, are based upon studies of small patient populations either assessed retrospectively or followed prospectively for relatively short periods2-4.
Outcome Measures
Outcome measures used in the assessment of AS have not been validated in PsA, and assumptions of equivalent utility may be false. For example, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were significantly lower in PsA than in AS and correlated poorly with external indicators of disease activity5. In addition, spinal assessments have shown poor sensitivity and specificity for sacroiliac joint measures, including Schober's test and its modifications, chest expansion, cervical range of movement, and sacroiliac joint tenderness. Sensitivity to change and minimal clinically significant differences have not been established6.
Outcome measures in axPsA are under active assessment; however, the Assessments in Ankylosing Spondylitis (ASAS) Working Group has developed response criteria for improvement in AS, and by consensus, these will be used in this review7. ASAS has validated composite measures measuring disease activity (BASDAI), function (Bath AS Functional Index, BASFI), patient global assessment (Bath AS Global Index, BASGI), and spinal mobility (Bath AS Metrology Index, BASMI). Structural damage is evaluated using validated radiographic instruments (Bath AS Radiology Index/Stoke AS Spine Score, BASRI/SASSS)7.
Search Strategy
A literature search of Medline, EMBASE, CINHAL, and the Cochrane Library from 1966 to 2005 was done using the key MeSH terms ankylosing spondylitis, psoriatic arthritis, axial disease, spondyloarthropathy (SpA), psoriasis, spondylitis, and antirheumatic therapy, alone and in combination, and of the following terms with PsA, SpA, or spondylitis: salazopyrine, methotrexate, physiotherapy, pamidronate, gold oral and intramuscular, azathioprine, cyclosporine, hydroxychloroquine, infliximab, etanercept, adalimumab, and tumor necrosis factor (TNF).
The resulting database was culled for articles specifically addressing axial disease and its therapy in psoriasis, PsA, AS, or SpA. Abstracts from annual meetings of the American College of Rheumatology and the European Congress of Rheumatology were admitted as evidence if sufficient detail was available to determine level of evidence.
RESULTS
Physiotherapy — Level of Evidence 1a, Grade A
In a review of 6 trials of physiotherapy in AS (561 participants), supervised group physical therapy significantly improved global health and functioning, pain, and stiffness compared with home-based individual exercise8. In 2 trials, individualized home exercise programs had greater effects on spinal mobility and physical function, compared with no intervention. In 3 trials, supervised group physiotherapy produced better patient global assessments, compared with home-exercise programs. In another study, 3 weeks of inpatient spa-exercise therapy followed by 37 weeks of weekly outpatient group physiotherapy (without spa) showed evidence for effects on pain, physical function, and patient global assessment, compared with outpatient group physiotherapy alone. An additional trial of a home-based exercise and disease education package showed benefit for spinal mobility and function in AS9.
Nonsteroidal Antiinflammatory Drugs
Nonsteroidal antiinflammatory drugs (NSAID) appear to be rapidly efficacious in relieving signs and symptoms of pain and morning stiffness (level of evidence 1a, grade A) in axial disease. Continuous NSAID usage can reduce radiological progression (level of evidence 1b, grade A), although separate treatments for inflammation and progression of structural damage have been suggested10.
Coxibs may have fewer gastrointestinal side effects, but cardiovascular issues may nullify that benefit. Equivalent efficacy has been demonstrated for one coxib11, and superior efficacy over 12 months for etoricoxib over a nonselective NSAID (naproxen) has been shown (level of evidence 1b, grade A)12. Two NSAID at maximum recommended/tolerated and continuous doses are recommended before concluding that a patient is NSAID refractory (level of evidence 4, grade C).
Simple Analgesia
No disease-specific evidence supports paracetamol or other analgesics in axial disease of AS or PsA.
Corticosteroids
Significant benefit has been noted with intraarticular glucocorticoids for active peripheral arthritis (level of evidence 4, grade C) and given under fluoroscopic or computer tomographic guidance into the sacroiliac joints (level of evidence 1b, grade A). A dose-response, double-blind comparison of 1 g versus 375 mg of methylprednisolone given as 3 consecutive daily intravenous (IV) infusions demonstrated no significant differences13. Open studies evaluating pulse IV methylprednisolone 1 g for 3 consecutive days have demonstrated prompt improvement lasting 3–21 months (level of evidence 2b, grade B)14.
Disease Modifying Antirheumatic Drugs
Sulfasalazine (SSZ). Sulfasalazine has been studied in PsA, but only small percentages of patients had axial involvement, and responses were poorly documented. In a review of 12 controlled trials of SSZ, improvement in erythrocyte sedimentation rate (ESR) and morning stiffness favored SSZ over placebo (level of evidence 1a, grade A)15. In the largest and longest of these trials (221 patients, 36-week course)16, improvement was significant (p = 0.01) but modest, with 55% and 45% improvements in the PsA response criteria for SSZ and placebo, respectively. The action of SSZ appears to be confined to peripheral arthritis with no evidence of benefit in axial disease (level of evidence 1a, grade A).
A single trial evaluated SSZ in primary outcome analyses of back pain, chest expansion, occiput-to-wall test, and patients' general well-being. Compared with other trials, patients in this study had more peripheral arthritis and the highest level of baseline ESR, but the shortest disease duration. Withdrawals for side effects with SSZ were significant. Spondylitis was not improved, and radiological progression was not retarded with SSZ16.
Oral formulations of 5-ASA (pentasa and asacol) have been examined in open trials in AS without benefit17.
Methotrexate (MTX). The efficacy of MTX in PsA was first described in 1964, but benefit has not been demonstrated in axial disease (level of evidence 1a, grade A). A 3 month, double-blind, placebo-controlled study of parenteral MTX in 21 patients who had active skin disease and peripheral arthritis showed significant improvement in joint tenderness and range of motion, extent of skin involvement, and ESR18.
In a randomized, double-blind, placebo-controlled trial comparing oral low dose pulse MTX with placebo, the only significant response was the physician assessment of arthritis activity19. In a 24-month study of 38 patients, MTX did not show improvement in radiographic progression compared with matched controls20.
In a randomized, double-blind placebo-controlled trial of 70 patients with AS, MTX showed significant benefit over 24 weeks in physical well-being, BASDAI, BASFI, physician global assessment, patient global assessment, spinal pain, and Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) (level of evidence 1b, grade A)21.
The toxicity, particularly hepatotoxicity, of MTX in psoriasis and PsA has been compared with that in RA. A retrospective study of 104 patients followed over 2 decades did not suggest increased toxicity22. However, analysis is difficult: studies tend to be retrospective, with no controlling for alcohol consumption; older studies include daily therapy; and many do not include folic acid supplementation. No consensus exists as to the indications for liver biopsy either before treatment or at specified intervals during treatment.
Gold salts and antimalarial drugs. Anecdotal case reports have shown no benefit for gold salts and antimalarial drugs in axPsA23,24.
Azathioprine. Azathioprine was associated with a low response rate and a high withdrawal rate due to adverse effects25.
Thalidomide (level of evidence 3, grade B). A one-year, open-label trial of thalidomide was conducted in 30 men with treatment-refractory AS. Of 26 patients who completed the study, 80% showed > 20% improvement in 3–6 months; 9 patients became pain-free. Peripheral neuropathy and teratogenicity remain major limitations26.
Leflunomide (level of evidence 1b, grade A for non-benefit). A randomized, placebo-controlled, 6-month trial of leflunomide in 45 patients with AS showed no significant benefit, and axial disease was not assessed27.
Cyclosporine (level of evidence 3, grade B). A review of 16 studies of cyclosporine therapy in PsA showed improvements in rash and peripheral arthritis, without evaluating axial disease28. The addition of cyclosporine to MTX nonresponders significantly improved peripheral joint scores, but axial disease was not evaluated29.
Bisphosphonates (level of evidence 1b, grade A). One randomized, controlled, single-center study and 2 open analyses examined IV pamidronate in NSAID-refractory AS patients. In a 6-month, double-blind, dose-response comparison, 60 mg had significant benefit over 10 mg IV pamidronate; 40% of patients had a 50% BASDAI reduction, but no significant reduction in peripheral pain30.
Biological Therapies
Interleukin 1 receptor antagonist anakinra (level of evidence 3, grade B). An open-label, 3-month pilot study of anakinra in 9 patients showed significant improvements in ASAS 20% response (BASFI, BASDAI, AS Quality of Life, C-reactive protein, and ESR), and significant improvement in enthesitis and osteitis lesions as measured by magnetic resonance imaging (MRI)31.
Anti-TNF therapy. Trial evidence shows etanercept, infliximab, and adalimumab provide significant improvement in disease activity, range of motion, physical function, and quality of life, both as monotherapy and as add-on therapy to other disease modifying antirheumatic drugs in both psoriasis and PsA32-40. All 3 agents retard radiologic progression in PsA. Axial disease was not studied, as too few patients had spondylitis. In AS trials, few patients had psoriasis (5–15%), and ASAS 20 responses were inferior in this subset.
Etanercept trials in PsA and AS showed improvements in symptoms and signs of disease, mobility, physical function, and acute phase reactants, with complete resolution or improvement noted in 86% of lesions, documented by MRI, in the AS trial (level of evidence 1a, grade A)32-34.
Infliximab trials in PsA have shown significant response in NSAID-refractory patients (those with long-standing, severe disease), and benefit was maintained up to 24 months with continued therapy (level of evidence 1a, grade A)35-37.
Adalimumab therapy in 315 PsA patients treated for 6 months showed significant improvements in joint and skin manifestations, improved quality of life, and retardation of radiological progression (level of evidence 1b, grade A). Only one patient in this study, however, had axial disease38-40.
TREATMENT RECOMMENDATIONS AND CONCLUSIONS
Validated outcome measures and formal trials in adequate numbers of patients with axPsA are urgently needed to address the safety and efficacy of treatments for axPsA. At present, the ASAS specifications and definitions for diagnosis, assessment of disease, treatment failure, treatment contraindications, and assessment of response are recommended and are summarized as follows:
Treatment Algorithm41,42
1. Establish diagnosis of PsA.
2. Initiate therapy with physiotherapy and continuous NSAID for clinically symptomatic axial disease.
3. Consider corticosteroid injection to symptomatic sacroiliac joint.
4. If axial disease is persistent, particularly with radiological evidence, commence anti-TNF therapy, with attention to contraindications and appropriate monitoring.
5. Other considerations include methotrexate (with appropriate monitoring) or pamidronate (intravenous infusions).
Until further evidence is available, infliximab, etanercept, and adalimumab are suggested for reduction of signs and symptoms of moderate to severely active axPsA in patients with an inadequate response to at least 2 NSAID. Either SSZ or MTX are suggested in patients with predominantly active peripheral arthritis.
Efficacy, effect size, and number needed to treat have been recently reviewed42. As trial evidence becomes available in patients with PsA with specific axial involvement, these recommendations can be reviewed without the necessity of using AS surrogates.
1. Battistone MJ, Manaster BJ, Reda DJ, Clegg DO. The prevalence of sacroiliitis in psoriatic arthritis: new perspectives from a large, multicenter cohort. A Department of Veterans Affairs Cooperative Study. Skeletal Radiol 1999;28:196-201. [MEDLINE]
2. Hanly JG, Russell ML, Gladman DD. Psoriatic spondyloarthropathy: a long term prospective study. Ann Rheum Dis 1988;47:386-93. [MEDLINE]3. Helliwell PS, Hickling P, Wright V. Do the radiological changes of classic ankylosing spondylitis differ from the changes found in the spondylitis associated with inflammatory bowel disease, psoriasis, and reactive arthritis? Ann Rheum Dis 1998;57:135-40.[MEDLINE]
4. Gladman DD, Brubacher B, Buskila D, Langevitz P, Farewell VT. Differences in the expression of spondyloarthropathy: a comparison between ankylosing spondylitis and psoriatic arthritis. Clin Invest Med 1993;16:1-7. [MEDLINE]
5. Taylor WJ, Harrison AA. Could the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) be a valid measure of disease activity in patients with psoriatic arthritis? Arthritis Rheum 2004;51:311-5. [MEDLINE]
6. Gladman DD, Cook RJ, Schentag C, et al. The clinical assessment of patients with psoriatic arthritis: results of a reliability study of the Spondyloarthritis Research Consortium of Canada. J Rheumatol 2004;31:1126–31. [MEDLINE]
7. Braun J, Sieper J. Building consensus on nomenclature and disease classification for ankylosing spondylitis: results and discussion of a questionnaire prepared for the International Workshop on New Treatment Strategies in Ankylosing Spondylitis, Berlin, Germany, 18–19 January 2002. Ann Rheum Dis 2002;61 Suppl III:iii61–7.
8. Dagfinrud H, Hagen KB, Kvien TK. Physiotherapy interventions for ankylosing spondylitis. The Cochrane Database of Systematic Reviews 2004; Issue 4: Art. No: CD002822. doi: 10.1002/14651858.CD002822.pub2.
9. Hidding A, van der Linden S, Gielen X, de Witte L, Dijkmans B, Moolenburgh D. Continuation of group physical therapy is necessary in ankylosing spondylitis: results of a randomized controlled trial. Arthritis Care Res 1994;7:90–6. [MEDLINE]
10. Wanders A, van der Heijde D, Landewe R, et al. Nonsteroidal anti-inflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 2005;52:1756–65. [MEDLINE]
11. Dougados M, Behier JM, Jolchine I, et al. Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal anti-inflammatory drug. Arthritis Rheum 2001;44:180-5.[MEDLINE]
12. van der Heijde D, Baraf HS, Ramos-Remus C, et al. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two–week, randomized, controlled study. Arthritis Rheum 2005;52:1205-15. [MEDLINE]
13. Peters ND, Ejstrup L. Intravenous methylprednisolone pulse therapy in ankylosing spondylitis. Scand J Rheumatol 1992;21:134-8. [MEDLINE]
14. Mintz G, Enriquez RD, Mercado U, Robles EJ, Jimenez FJ, Gutierrez G. Intravenous methylprednisolone pulse therapy in severe ankylosing spondylitis. Arthritis Rheum 1981;24:734-6.[MEDLINE]
15. Ferraz MB, Tugwell P, Goldsmith CH, Atra E. Metaanalysis of sulfasalazine in ankylosing spondylitis. J Rheumatol 1990;17:1482-6. [MEDLINE]
16. Clegg DO, Reda DJ, Weisman MH, et al. Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veteran Affairs Cooperative Study. Arthritis Rheum 1996;39:2004-12. [MEDLINE]
17. Dekker-Saeys BJ, Dijkmans BA, Tytgat GN. Treatment of spondyloarthropathy with 5 aminosalicyclic acid (mesalazine): an open trial. J Rheumatol 2000;27:723-6. [MEDLINE]
18. Ostendorf B, Specker C, Schneider M. Methotrexate lacks efficacy in the treatment of severe ankylosing spondylitis compared with rheumatoid and psoriatic arthritis. J Clin Rheumatol 1998;4:129-36.
19. Willkens RF, Williams HJ, Ward JR, et al. Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Arthritis Rheum 1984;27:376-81. [MEDLINE]
20. Abu-Shakra M, Gladman DD, Thorne JC, Long J, Gough J, Farewell VT. Longterm methotrexate therapy in psoriatic arthritis: clinical and radiological outcome. J Rheumatol 1995;22:241-5.[MEDLINE]
21. Gonzalez-Lopez L, Garcia-Gonzalez A, Vazquez-Del-Mercado M, Munoz-Valle JF, Gamez-Nava JI. Efficacy of methotrexate in ankylosing spondylitis. A randomized, double blind, placebo controlled trial. J Rheumatol 2004;31:1568-74. [MEDLINE]
22. Wollina U, Stander K, Barta U. Toxicity of methotrexate treatment in psoriasis and psoriatic arthritis — short and long term toxicity in 104 patients. Clin Rheumatol 2001;20:406-10.[MEDLINE]
23. Grasedyck K, Schattenkirchner M, Bandilla K. The treatment of ankylosing spondylitis with auranofin (Ridaura). Z Rheumatol 1990;49:98-9. [MEDLINE]
24. Palit J, Hill J, Capell HA, et al. A multicentre double blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis. Br J Rheumatol 1990;29:280-3. [MEDLINE]
25. Jones G, Crotty M, Brooks P. Psoriatic arthritis: a quantitative overview of therapeutic options. Psoriatic Arthritis Meta-Analysis Study Group. Br J Rheumatol 1997;36:95-9. [MEDLINE]
26. Wei JC, Chan TW, Lin HS, Huang F, Chou CT. Thalidomide for severe refractory ankylosing spondylitis: a 6-month open-label trial. J Rheumatol 2003;30:2627-31. [MEDLINE]
27. Van Denderen JC, Van der Paardt M, Nurmohamed MT, et al. Double-blind, randomised, placebo-controlled study of leflunomide in the treatment of active ankylosing spondylitis. Ann Rheum Dis 2005 [epub ahead of print].
28. Olivieri I, Salvarani C, Cantini F, Macchioni L, Padula A, Niccoli L. Therapy with cyclosporine in psoriatic arthritis. Semin Arthritis Rheum 1997;27:36-43. [MEDLINE]
29. Fraser AD, van Kuijk AW, Westhovens R, et al. A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus cyclosporin in patients with active psoriatic arthritis. Ann Rheum Dis 2005;64:859-64. [MEDLINE]
30. Maksymowych WP, Jhangri GS, Fitzgerald AA, et al. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum 2002;46:766-73.[MEDLINE]
31. Tan AL, Marzo-Ortega H, O'Connor P, Fraser A, Emery P, McGonagle D. Efficacy of anakinra in active ankylosing spondylitis: a clinical and magnetic resonance imaging study. Ann Rheum Dis 2004;63:1041–5. [MEDLINE]
32. Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B, Burge DJ. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000;356:385–90. [MEDLINE]
33. Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004;50:2264-72. [MEDLINE]
34. Davis JC Jr, van der Heijde D, Braun J, et al. Enbrel Ankylosing Spondylitis Study Group. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 2003;48:3230-6. [MEDLINE]
35. Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002;359:1187–93. [MEDLINE]
36. van der Heijde D, Dijkmans B, Geusens P, et al. Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study Group. Efficacy and safety of infliximab in patients with ankylosing spondylitis. Results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005;52:582-91.[MEDLINE]
37. Antoni CE, Kavanaugh A, Kirkham B, et al. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT). Arthritis Rheum 2005;52:1227-36. [MEDLINE]
38. Mease PJ, Gladman DD, Ritchlin CT, et al. Adalimumab therapy in patients with psoriatic arthritis: 24-week results of a phase III study ADEPT — Adalimumab Effectiveness in Psoriatic Arthritis Trial [abstract]. Arthritis Rheum 2004;51 Suppl.
39. Mease P, Gladman D, Ritchlin C, Ruderman E, Steinfeld S, Choy E. Adalimumab for the treatment of psoriasis with moderately to severely active psoriatic arthritis. Arthritis Rheum 2005;52:3279-89. [MEDLINE]
40. Mease P, Sharp J, Ory P, et al. Adalimumab treatment effects on radiographic progression of joint disease in patients with psoriatic arthritis: results from ADEPT [abstract]. EULAR 2005; F0212.
41. Braun J, Pham T, Sieper J, et al. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 2003;62:817–24. [MEDLINE]
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