Profile of the use of disease modifying drugs in the Brazilian Registry of Spondyloarthritides

Charles L. Kohem Adriana B. Bortoluzzo Célio R. Gonçalves José Antonio Braga da Silva Antonio Carlos Ximenes Manoel B. Bértolo Sandra L.E. Ribeiro Mauro Keiserman Rita Menin Thelma L. Skare Sueli Carneiro Valderílio F. Azevedo Walber P. Vieira Elisa N. Albuquerque Washington A. Bianchi Rubens Bonfiglioli Cristiano Campanholo Hellen M. S. Carvalho Izaias Pereira da Costa Angela L. B. Pinto Duarte Nocy H. Leite Sonia A. L. Lima Eduardo S. Meirelles Ivânio A. Pereira Marcelo M. Pinheiro Elizandra Polito Gustavo G. Resende Francisco Airton C. Rocha Mittermayer B. Santiago Maria de Fátima L. C. Sauma Valéria Valim Percival D. Sampaio-Barros About the authors

Abstracts

Introdução:

Poucos estudos avaliaram o perfil do uso de drogas modificadoras de doença (DMD) em pacientes brasileiros com diagnóstico de espondiloartrite (EpA).

Métodos:

Um protocolo comum de investigação foi prospectivamente aplicado em 1505 pacientes classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartrites (ESSG), acompanhados em 29 centros de referência em Reumatologia no Brasil. Variáveis clínicas e demográficas foram obtidas e avaliadas, analisando-se suas correlações com o uso das DMD metotrexato (MTX) e sulfasalazina (SSZ).

Resultados:

Pelo menos uma DMD foi utilizada por 73,6% dos pacientes, sendo MTX por 29,2% e SSZ por 21,7%, enquanto 22,7% utilizaram ambas as drogas. O uso do MTX foi significativamente associado ao acometimento periférico, e a SSZ foi associada ao comprometimento axial, sendo que as duas drogas foram mais utilizadas, isoladas ou combinadas, no comprometimento misto (p < 0,001). O uso de uma DMD esteve significativamente associado à etnia branca (MTX; p = 0,014), lombalgia inflamatória (SSZ; p = 0,002), dor em nádegas (SSZ; p = 0,030), cervicalgia (MTX; p = 0,042), artrite de membros inferiores (MTX; p < 0,001), artrite de membros superiores (MTX; p < 0,001), entesite (p = 0,007), dactilite (MTX; p < 0,001), doença inflamatória intestinal (SSZ; p < 0,001) e acometimento ungueal (MTX; p < 0,001).

Conclusão:

O uso de pelo menos uma DMD foi referido por mais de 70% dos pacientes numa grande coorte brasileira de pacientes com EpA, sendo o uso do MTX mais associado ao acometimento periférico e o uso da SSZ mais associado ao acometimento axial.

Espondiloartrites; Tratamento; Drogas modificadoras de doença; Metotrexato; Sulfasalazina


Introduction:

Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA).

Methods:

A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ).

Results:

At least one DMD was used by 73.6 % of patients: MTX by 29.2 % and SSZ by 21.7%, while 22.7 % used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001).

Conclusion:

The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Sspondyloarthritides; Treatment; Disease modifying drugs; Methotrexate; Sulfasalazine


Introduction

Spondyloarthritides are a group of chronic inflammatory diseases with similar clinical and genetic characteristics, which allows their analysis within the same group. Ankylosing spondylitis (AS) is a disease with predominantly axial clinical impairment, while psoriatic arthritis (PA), reactive arthritis, arthritis associated with inflammatory bowel disease and undifferentiated SpA often show an important peripheral involvement.11. Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: A guide to assess spondyloarthritis. Ann Rheum Dis 2009;68(Suppl. II):ii1-ii44. Recognizing this extension of the concept itself, SpAs were recently classified into axial22. Rudwaleit M, van der Heijde D, Landewé R, Listing J, Brandt J, Braun J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:770-76. and peripheral33. Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT et al. The development of Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis. Ann Rheum Dis 2011;70:25-31.. The evaluation of Brazilian44. Sampaio-Barros PD, Gonçalves CR, Braga da Silva JA, Ximenes AC, Azevedo VC, Bianchi WA. Registro Iberoamericano de Espondiloartritis (RESPONDIA): Brasil. Reumatol. Clin. 2008;4(Supl. 4):30-35. and Latin American55. Benegas M, Muñoz-Gomariz E, Font P, Burgos-Vargas R, Chaves J, Palleiro D, et al. Comparison of the clinical expression of patients with ankylosing spondylitis from Europe and Latin America. J Rheumatol 2012;39:2315-2320. patients with SpA reveals that, besides the characteristic axial involvement, often a significant number of patients with peripheral involvement are detected.

Studies evaluating the treatment of SpA, especially AS66. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 2010 Update of the ASAS / EULAR recommendations for the management of ankylosing spondyltis. Ann Rheum Dis 2011;70:896-904.,77. Sampaio-Barros PD, Pinheiro MM, Ximenes AC, Meirelles ES, Keiserman M, Azevedo VF et al. Recomendações sobre o tratamento da espondilite anquilosante. Rev Bras Reumatol 2013;53:242-57. and PA,88. Gossec L, Smolen JS, Gaujoux-Viala C, Ash Z, Marzo-Ortega H, van der Heijde D, et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis 2012;71:4-12.,99. Carneiro S, Azevedo VF, Bonfiglioli R, Ranza R, Gonçalves CR, Keiserman CR et al. Recomendações sobre o tratamento da artrite psoriásica. Rev Bras Reumatol 2013;53:227-41. show that the use of disease-modifying drugs (DMD), such as methotrexate, sulfasalazine, and leflunomide, is related more to the involvement of the peripheral versus axial involvement.

This study analyzes the prescription of DMD for a large cohort of Brazilian patients with SpA.

Patients and methods

This is a prospective, observational, multicenter study with 1505 patients from 29 referral centers participating in the Registro Brasileiro de Espondiloartrites (RBE). All patients fulfilled the criteria of the European Group for the Study of Spondyloarthropathies (ESSG).1010. Dougados M, van der Linden S, Julin R, Huitfeld B, Amor B, Calin A et al. The European Spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy. Arthritis Rheum 1991;34:1218-27. Data were collected from June 2006 to December 2009. The BRS participates in RESPONDIA (Registro Iberoamericano de Espondiloartrites) group, consisting of nine Latin American countries (Argentina, Brazil, Costa Rica, Chile, Ecuador, Mexico, Peru, Uruguay and Venezuela) and the two countries of the Iberian Peninsula (Spain and Portugal) .

The joint investigation protocol included demographic (gender, race, family history, HLA-B27), osteoarticular clinical (inflammatory back pain, buttock pain, neck pain, hip pain, lower extremity arthritis, arthritis of the lower limbs, enthesitis, dactylitis), extra-articular clinical (uveitis, inflammatory bowel disease [IBD], psoriasis, urethritis), and laboratory (erythrocyte sedimentation rate - ESR and C-reactive protein - CRP) variables.

Patients were evaluated for treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, DMD and biological agents. Regarding the use of DMD, methotrexate (MTX), sulfasalazine (SSZ) and leflunomide (LFN) were evaluated.

For the diagnosis of AS, New York criteria were used;1111. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8. for psoriatic arthritis, the patients had to meet the criteria of Moll and Wright.1212. Moll JMH, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55-78. The diagnosis of reactive arthritis was considered if were present: asymmetric oligoarthritis of the lower limbs with enthesopathies and/or inflammatory lumbar pain arousing after enteric or urogenital infection,1313. Kingsley G, Sieper J. Third International Workshop on Reactive Arthritis, 23-26 September 1995, Berlin, Germany. Ann Rheum Dis 1996;55:564-84. and spondylitis/arthritis associated with inflammatory bowel disease, if the patient showed inflammatory axial features and/ or peripheral joint involvement, associated with confirmed Crohn's disease or ulcerative colitis.

Statistical analysis. Categorical variables were compared using χ2 and Fisher exact test, and continuous variables were compared using ANOVA. A value of p <0.05 was considered significant, and 0.05> p> 0.10 was considered as statistical trend.

Results

Data analysis revealed that at least one DMD was used by 73.6% of patients; 51.9% reported the use of MTX - 29.2% as monotherapy and 22.7% with SSZ; and 44.4% used SSZ, of whom 21.7% as monotherapy. The use of leflunomide was reported by 0.2% of patients; for this reason, this agent was not included in the statistical analysis.

With respect to joint involvement, MTX was significantly associated with peripheral involvement and SSZ was associated with axial involvement, and the two drugs were used more often, as monotherapy or in combination, in the mixed involvement (p < 0.001) (Table 1).

Table 1
Results of using DMD, according to the clinical picture.

The demographic variables showed that MTX was associated with Caucasian ethnicity (p = 0.014). Gender, family history and HLA-B27 were not associated with the use of any DMD (Table 2).

Table 2
Results of using DMD, according to epidemiological data.

With respect to the clinical picture, MTX was significantly associated with cervical involvement (p = 0.042), arthritis of the lower limbs (p < 0.001), arthritis of the upper limbs (p < 0.001), cutaneous psoriasis (p < 0.001), dactylitis (p < 0.001) and nail involvement (p < 0.001). By the other hand, SSZ was associated with inflammatory back pain (p = 0.002), buttock pain (p = 0.030) and inflammatory bowel disease (p < 0.001), while the use of both drugs was associated with enthesites (p = 0.007). Coxofemoral pain, anterior uveitis and urethritis showed no association with the use of DMD (Table 3).

Table 3
Results of using DMD, according to the clinical data.

Discussion

This study confirms that the use of DMD is very common in Brazilian patients. In this multicenter study, which included patients from the five Brazilian regions (Southeast, South, Midwest, Northeast and North), the use of at least one DMD was reported by nearly three in four patients with SpA, with 51.7% to MTX and 44.4% to SSZ. The use of at least one DMD may be greatly associated with the significant number of patients with peripheral joint and mixed involvement observed in our cases.44. Sampaio-Barros PD, Gonçalves CR, Braga da Silva JA, Ximenes AC, Azevedo VC, Bianchi WA. Registro Iberoamericano de Espondiloartritis (RESPONDIA): Brasil. Reumatol. Clin. 2008;4(Supl. 4):30-35. A study evaluating 216 patients with AS in Turkey revealed that 77.5% received SSZ and 15% MTX, and 9% received anti-TNF agents.1414. Bodur H, Ataman S, Akbulut L, Evcik D, Kavuncu V, Kaya T, et al. Characteristics and medical management of patients with rheumatoid arthritis and ankylosing spondylitis. Clin Rheumatol 2008;27:1119-25.

The use of MTX has been studied in AS in the past two decades. Considering in general that its use is indicated for patients with predominantly axial involvement, the clinical response was not favorable;1515. Altan L, Bingöl U, Karakoç Y, Aydiner S, Yurtkuran M, Yurtkuran M. Clinical investigation of methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2001;30:255-9.

16. Marshall RW, Kirwan JR. Methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2001;30:313-4.
-1717. Roychowdhury B, Bintley-Bagot S, Bulgen DY, Thompson RN, Tunn EJ, Moots RJ. Is methotrexate effective in ankylosing spondylitis? Rheumatology (Oxford) 2002;41:1330-2. the only two studies that demonstrated a better response to MTX were Latin American: one Brazilian1818. Sampaio-Barros PD, Costallat LT, Bertolo MB, Marques-Neto JF, Samara AM. Methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2000;29:160-2. and one Mexican.1919. Gonzalez-Lopez L, Garcia-Gonzalez A, Vazquez-Del-Mercado M, Muñoz-Valle JF, Gomez-Nava JI. Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial. J Rheumatol 2004;31:1568-74. Also, the use of MTX for short period of time (16 weeks) might not be enough for the desired effect of the medication. On the other hand, MTX has been used for over 50 years in PA patients, with good results,2121. Abu-Shakra M, Gladman DD, Thorne JC, Long J, Gough J, Farewell VT. Long-term methotrexate therapy in psoriatic arthritis: clinical and radiological outcome. J Rheumatol 1995;22:241-5.

22. Scarpa R, Peluso R, Atteno M, Manguso F, Spanò A, Iervolino S, et al. The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: Results of a pilot randomised 6-month trial with methotrexate. Clin Rheumatol 2008;27:823-6.
-2323. Lie E, van der Heijde D, Uhlig T, Heiberg MS, Koldingsnes W, Rødevand E, et al. Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis. Ann Rheum Dis 2010;69:671-6. being the basal drug of first choice.

The present study confirmed this trend of MTX use in cases of peripheral involvement, associated or not with axial involvement. Statistical association with arthritis of the lower and upper limbs was noted. The association with Caucasians seems to be related to the presence of psoriasis and its sequels (dactylitis and nail involvement) as shown in the literature. 2424. Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimm 2010;34:314-21.,2525. Skare TL, Bortoluzzo AB, Gonçalves CR, Braga da Silva JA, Ximenes AC, Bértolo MB, et al. Ethnic influence in clinical and functional measures of Brazilian patients with spondyloarthritis. J. Rheumatol 2012;39:141-7.

Sulfasalazine is the most commonly used conventional DMD in AS.66. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 2010 Update of the ASAS / EULAR recommendations for the management of ankylosing spondyltis. Ann Rheum Dis 2011;70:896-904. Its use in AS comes from the 1980s, and its main action would be in cases of associated peripheral involvement.2626. Clegg DO, Reda DJ, Weisman MH, Blackburn WD, Cush JJ, Cannon GW, et al. Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996;39:2004-12.,2727. Chen J, Liu C. Is sulfasalazine effective in ankylosing spondylitis? A systematic review of randomized controlled trials. J Rheumatol 2006;33:722-31. The same action profile is observed in PA.2828. Gupta AK, Grober JS, Hamilton TA, Ellis CN, Siegel MT, Voorhees JJ, et al. Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial. J Rheumatol 1995;22:894-8.

29. Combe B, Goupille P, Kuntz JL, Tebib J, Lioté F, Bregeon C. Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study. Br J Rheumatol 1996;35:664-8.
-3030. Clegg DO, Reda DJ, Mejias E, Cannon GW, Weisman MH, Taylor T, et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996;39:2004-12. SSZ is also used in the case of reactive arthritis with gastrointestinal etiology3131. Clegg DO, Reda DJ, Weisman MH, Cush JJ, Vasey FB, Schumacher HR Jr, et al. Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996;39:2021-7. and in the arthritides associated with inflammatory bowel disease.3232. Brazilian Study Group of Inflammatory Bowel Diseases. Consensus guidelines for the management of inflammatory bowel disease. Arq Gastroenterol 2010;47:313-25..3333. D'Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: When to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol 2011;106:199-212. In contrast to what is traditionally observed in the literature, the use of SSZ in the present study was associated with axial involvement, particularly inflammatory low back pain and buttock pain, and with enteropathic arthritis.

However, although SSZ is significantly more used than MTX in patients with inflammatory bowel disease, it is noteworthy that less than 9% of patients with this type of impairment were using SSZ. The explanation for this use in patients with axial involvement lies in the fact that many rheumatology services in Brazil use empirically at least one DMD, preferably SSZ, in patients with AS, before prescribing biological agents, since we have an impressive number of patients with mixed (axial and peripheral) joint involvement. Regarding the entheseal involvement, quite frequent in our series,3434. Carneiro S, Bortoluzzo AB, Gonçalves CR, Braga da Silva JA, Ximenes AC, Bértolo MB, et al. Impact of enthesitis in 1505 Brazilian patients with spondyloarthritis. J Rheumatol 2013;40:1719-25. is common practice the prescription of both MTX and SSZ, as monotherapy or in combination, for its treatment.

References

  • 1
    Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: A guide to assess spondyloarthritis. Ann Rheum Dis 2009;68(Suppl. II):ii1-ii44.
  • 2
    Rudwaleit M, van der Heijde D, Landewé R, Listing J, Brandt J, Braun J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:770-76.
  • 3
    Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT et al. The development of Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis. Ann Rheum Dis 2011;70:25-31.
  • 4
    Sampaio-Barros PD, Gonçalves CR, Braga da Silva JA, Ximenes AC, Azevedo VC, Bianchi WA. Registro Iberoamericano de Espondiloartritis (RESPONDIA): Brasil. Reumatol. Clin. 2008;4(Supl. 4):30-35.
  • 5
    Benegas M, Muñoz-Gomariz E, Font P, Burgos-Vargas R, Chaves J, Palleiro D, et al. Comparison of the clinical expression of patients with ankylosing spondylitis from Europe and Latin America. J Rheumatol 2012;39:2315-2320.
  • 6
    Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 2010 Update of the ASAS / EULAR recommendations for the management of ankylosing spondyltis. Ann Rheum Dis 2011;70:896-904.
  • 7
    Sampaio-Barros PD, Pinheiro MM, Ximenes AC, Meirelles ES, Keiserman M, Azevedo VF et al. Recomendações sobre o tratamento da espondilite anquilosante. Rev Bras Reumatol 2013;53:242-57.
  • 8
    Gossec L, Smolen JS, Gaujoux-Viala C, Ash Z, Marzo-Ortega H, van der Heijde D, et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis 2012;71:4-12.
  • 9
    Carneiro S, Azevedo VF, Bonfiglioli R, Ranza R, Gonçalves CR, Keiserman CR et al. Recomendações sobre o tratamento da artrite psoriásica. Rev Bras Reumatol 2013;53:227-41.
  • 10
    Dougados M, van der Linden S, Julin R, Huitfeld B, Amor B, Calin A et al. The European Spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy. Arthritis Rheum 1991;34:1218-27.
  • 11
    van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8.
  • 12
    Moll JMH, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55-78.
  • 13
    Kingsley G, Sieper J. Third International Workshop on Reactive Arthritis, 23-26 September 1995, Berlin, Germany. Ann Rheum Dis 1996;55:564-84.
  • 14
    Bodur H, Ataman S, Akbulut L, Evcik D, Kavuncu V, Kaya T, et al. Characteristics and medical management of patients with rheumatoid arthritis and ankylosing spondylitis. Clin Rheumatol 2008;27:1119-25.
  • 15
    Altan L, Bingöl U, Karakoç Y, Aydiner S, Yurtkuran M, Yurtkuran M. Clinical investigation of methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2001;30:255-9.
  • 16
    Marshall RW, Kirwan JR. Methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2001;30:313-4.
  • 17
    Roychowdhury B, Bintley-Bagot S, Bulgen DY, Thompson RN, Tunn EJ, Moots RJ. Is methotrexate effective in ankylosing spondylitis? Rheumatology (Oxford) 2002;41:1330-2.
  • 18
    Sampaio-Barros PD, Costallat LT, Bertolo MB, Marques-Neto JF, Samara AM. Methotrexate in the treatment of ankylosing spondylitis. Scand J Rheumatol 2000;29:160-2.
  • 19
    Gonzalez-Lopez L, Garcia-Gonzalez A, Vazquez-Del-Mercado M, Muñoz-Valle JF, Gomez-Nava JI. Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial. J Rheumatol 2004;31:1568-74.
  • 20
    Haibel H, Brandt HC, Song IH, Brandt A, Listing J, Rudwaleit M, Sieper J. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis. 2007;66:419-21.
  • 21
    Abu-Shakra M, Gladman DD, Thorne JC, Long J, Gough J, Farewell VT. Long-term methotrexate therapy in psoriatic arthritis: clinical and radiological outcome. J Rheumatol 1995;22:241-5.
  • 22
    Scarpa R, Peluso R, Atteno M, Manguso F, Spanò A, Iervolino S, et al. The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: Results of a pilot randomised 6-month trial with methotrexate. Clin Rheumatol 2008;27:823-6.
  • 23
    Lie E, van der Heijde D, Uhlig T, Heiberg MS, Koldingsnes W, Rødevand E, et al. Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis. Ann Rheum Dis 2010;69:671-6.
  • 24
    Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimm 2010;34:314-21.
  • 25
    Skare TL, Bortoluzzo AB, Gonçalves CR, Braga da Silva JA, Ximenes AC, Bértolo MB, et al. Ethnic influence in clinical and functional measures of Brazilian patients with spondyloarthritis. J. Rheumatol 2012;39:141-7.
  • 26
    Clegg DO, Reda DJ, Weisman MH, Blackburn WD, Cush JJ, Cannon GW, et al. Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996;39:2004-12.
  • 27
    Chen J, Liu C. Is sulfasalazine effective in ankylosing spondylitis? A systematic review of randomized controlled trials. J Rheumatol 2006;33:722-31.
  • 28
    Gupta AK, Grober JS, Hamilton TA, Ellis CN, Siegel MT, Voorhees JJ, et al. Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial. J Rheumatol 1995;22:894-8.
  • 29
    Combe B, Goupille P, Kuntz JL, Tebib J, Lioté F, Bregeon C. Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study. Br J Rheumatol 1996;35:664-8.
  • 30
    Clegg DO, Reda DJ, Mejias E, Cannon GW, Weisman MH, Taylor T, et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996;39:2004-12.
  • 31
    Clegg DO, Reda DJ, Weisman MH, Cush JJ, Vasey FB, Schumacher HR Jr, et al. Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996;39:2021-7.
  • 32
    Brazilian Study Group of Inflammatory Bowel Diseases. Consensus guidelines for the management of inflammatory bowel disease. Arq Gastroenterol 2010;47:313-25.
  • 33
    D'Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: When to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol 2011;106:199-212.
  • 34
    Carneiro S, Bortoluzzo AB, Gonçalves CR, Braga da Silva JA, Ximenes AC, Bértolo MB, et al. Impact of enthesitis in 1505 Brazilian patients with spondyloarthritis. J Rheumatol 2013;40:1719-25.

Publication Dates

  • Publication in this collection
    Jan-Feb 2014

History

  • Received
    28 Jan 2013
  • Accepted
    23 June 2013
Sociedade Brasileira de Reumatologia Av Brigadeiro Luiz Antonio, 2466 - Cj 93., 01402-000 São Paulo - SP, Tel./Fax: 55 11 3289 7165 - São Paulo - SP - Brazil
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