Advertisement

Steroid-free remission in lupus: myth or reality; an observational study from a tertiary referral centre

  • Rudra Prosad Goswami
  • Hiramanik Sit
  • Parasar Ghosh
  • Geetabali Sircar
  • Alakendu Ghosh
Original Article
  • 6 Downloads

Abstract

Objective

Whether maintaining steroid-free remission is feasible in Indian patients with systemic lupus erythematosus (SLE).

Methods

In 148 patients with SLE including 78 lupus nephritis (LN) previously put into remission, steroid therapy was gradually tapered off.

Results

Patients received glucocorticoids for median 1855 days (interquartile range (IQR) 901–2834) before discontinuing. Median duration of follow-up was 539 days (IQR 266.25–840.75). Flare occurred in 31 patients (20.9%; 95% confidence interval (CI) 15.17–28.19, renal flare in 12.16% (18/148, 95% CI 7.83–18.41)). Most of the flares occurred in the first year of follow-up (41.9%, 13/31). Overall 93.5% (29/31) of flares occurred in those who received ≤ 8 years of glucocorticoids, compared to 6.5% (2/31) of flares in others (p = 0.009). Median flare-free survival was 611 days (95% CI 518–704). Multivariate Cox regression identified the following predictors of flare-free survival: duration of disease (hazard ratio (HR) 0.89, 95% CI 0.84–0.94, p < 0.001), duration of glucocorticoid before discontinuing (HR 1.000086, 95% CI 1.000047–1.00012, p < 0.001) and second immunosuppressive (HR 1.89, 95% CI 1.251–2.87, p = 0.003). Additional risk factors of a renal flare-free survival among patients with LN were initial dose of glucocorticoids (HR 0.97, 95% CI 0.94–0.99, p = 0.005) and presence of haemolytic anaemia (HR 2.43, 95% CI 1.067–5.54, p = 0.035).

Conclusions

About 20% patients undergo exacerbation of disease activity after glucocorticoid withdrawal. Treatment for ≥ 8 years before discontinuing and an additional immunosuppressive agent improve the chance of flare-free survival.

Keywords

Flare-free survival Glucocorticoid Lupus nephritis Steroid-free-remission Systemic lupus erythematosus 

Notes

Compliance with ethical standards

Disclosures

None.

Supplementary material

10067_2018_4377_MOESM1_ESM.doc (75 kb)
ESM 1 (DOC 75 kb)

References

  1. 1.
    Hanly JG, Su L, Urowitz MB, Romero-Diaz J, Gordon C, Bae SC, Bernatsky S, Clarke AE, Wallace DJ, Merrill JT, Isenberg DA, Rahman A, Ginzler EM, Petri M, Bruce IN, Dooley MA, Fortin P, Gladman DD, Sanchez-Guerrero J, Steinsson K, Ramsey-Goldman R, Khamashta MA, Aranow C, Alarcón GS, Fessler BJ, Manzi S, Nived O, Sturfelt GK, Zoma AA, van Vollenhoven RF, Ramos-Casals M, Ruiz-Irastorza G, Lim SS, Kalunian KC, Inanc M, Kamen DL, Peschken CA, Jacobsen S, Askanase A, Theriault C, Farewell V (2016) Longitudinal analysis of outcomes of lupus nephritis in an international inception cohort using a multistate model approach. Arthritis Rheumatol 68:1932–1944CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    RiverosFrutos A, Casas I, Rúa-Figueroa I, López-Longo FJ, Calvo-Alén J, Galindo M et al (2017) RELESSER group, part of the Spanish Society of Rheumatology Systemic Autoimmune Diseases Study Group (EASSER). Systemic lupus erythematosus in Spanish males: a study of the Spanish rheumatology society lupus registry (RELESSER) cohort. Lupus 26:698–706CrossRefGoogle Scholar
  3. 3.
    Moroni G, Quaglini S, Gallelli B, Banfi G, Messa P, Ponticelli C (2013) Progressive improvement of patient and renal survival and reduction of morbidity over time in patients with lupus nephritis (LN) followed for 20 years. Lupus 22:810–818CrossRefPubMedGoogle Scholar
  4. 4.
    Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association et al (2012) Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 71:1771–1782CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Moroni G, Gatto M, Raffiotta F, Binda V, Frangou E, Lightstone L, Boumpas DT (2018) Can we withdraw immunosuppressants in patients with lupus nephritis in remission? An expert debate. Autoimmun Rev 17:11–18CrossRefPubMedGoogle Scholar
  6. 6.
    Petri M, Purvey S, Fang H, Magder LS (2012) Predictors of organ damage in systemic lupus erythematosus: the Hopkins lupus cohort. Arthritis Rheum 64:4021–4028CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bruce IN, O'Keeffe AG, Farewell V, Hanly JG, Manzi S, Su L, Gladman DD, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Gordon C, Wallace DJ, Clarke AE, Bernatsky S, Ginzler EM, Isenberg DA, Rahman A, Merrill JT, Alarcón GS, Fessler BJ, Fortin PR, Petri M, Steinsson K, Dooley MA, Khamashta MA, Ramsey-Goldman R, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven RF, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Urowitz MB (2015) Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the systemic lupus international collaborating clinics (SLICC) inception cohort. Ann Rheum Dis 74:1706–1713CrossRefPubMedGoogle Scholar
  8. 8.
    Ward M (1999) Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 42:338–346CrossRefPubMedGoogle Scholar
  9. 9.
    Asanuma Y, Oeser A, Shintani AK, Turner E, Olsen N, Fazio S, Linton MRF, Raggi P, Stein CM (2003) Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 349:2407–2415CrossRefPubMedGoogle Scholar
  10. 10.
    Apostolopoulos D, Morand EF (2017) It hasn’t gone away: the problem of glucocorticoid use in lupus remains. Rheumatology (Oxford) 56(suppl_1):i114–i122Google Scholar
  11. 11.
    Karp I, Abrahamowicz M, Fortin PR, Pilote L, Neville C, Pineau CA, Esdaile JM (2008) Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus? Arthritis Rheum 59:169–175CrossRefPubMedGoogle Scholar
  12. 12.
    Ponticelli C, Moroni G, Banfi G (1988) Discontinuation of therapy in diffuse proliferative lupus nephritis. Am J Med 85:275CrossRefPubMedGoogle Scholar
  13. 13.
    Moroni G, Longhi S, Giglio E, Messa P, Ponticelli C (2013) What happens after complete withdrawal of therapy in patients with lupus nephritis. Clin Exp Rheumatol 31(4 Suppl 78):S75–S81PubMedGoogle Scholar
  14. 14.
    Galbraith L, Manns B, Hemmelgarn B, Walsh M (2014) The Steroids In the Maintenance of remission of Proliferative Lupus nephritis (SIMPL) pilot trial. Can J Kidney Health Dis 1:30CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR et al (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29(2):288–291PubMedGoogle Scholar
  17. 17.
    Moroni G, Gallelli B, Quaglini S, Banfi G, Rivolta E, Messa P, Ponticelli C (2006) Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up. Nephrol Dial Transplant 21:1541–1548CrossRefPubMedGoogle Scholar
  18. 18.
    Sharon E, Kaplan D, Diamond HS (1973) Exacerbation of systemic lupus erythematosus after withdrawal of azathioprine therapy. N Engl J Med 288:122–124CrossRefPubMedGoogle Scholar
  19. 19.
    Drenkard C, Villa AR, Garcia-Padilla C, Pérez-Vázquez ME, Alarcón-Segovia D (1996) Remission of systematic lupus erythematosus. Medicine (Baltimore) 75:88–98CrossRefGoogle Scholar
  20. 20.
    Pablos JL, Gutierrez-Millet V, Gomez-Reino JJ (1994) Remission of lupus nephritis with cyclophosphamide and late relapses following therapy withdrawal. Scand J Rheumatol 23(3):142–144CrossRefPubMedGoogle Scholar
  21. 21.
    Mosca M, Neri R, Giannessi S, Pasquariello A, Puccini R, Bencivelli W, Bombardieri S (2001) Therapy with pulse methylprednisolone and short course pulse cyclophosphamide for diffuse proliferative glomerulonephritis. Lupus 10:253–255CrossRefPubMedGoogle Scholar
  22. 22.
    AptekarRG DJL, Steinberg AD (1972) Exacerbation of SLE nephritis after cyclophosphamide withdrawal. N Engl J Med 286:1159–1160Google Scholar
  23. 23.
    Medina-Quiñones CV, Ramos-Merino L, Ruiz-Sada P, Isenberg D (2016) Analysis of complete remission in systemic lupus erythematosus patients over a 32-year period. Arthritis Care Res 68:981–987CrossRefGoogle Scholar
  24. 24.
    Grande JP (1998) Mechanisms of progression of renal damage in lupus nephritis: pathogenesis of renal scarring. Lupus 7:604–610CrossRefPubMedGoogle Scholar
  25. 25.
    Mok CC, Ying KY, Tang S, Leung CY, Lee KW, Ng WL, Wong RWS, Lau CS (2004) Predictors and outcome of renal flares after successful cyclophosphamide treatment for diffuse proliferative lupus glomerulonephritis. Arthritis Rheum 50:2559–2568CrossRefPubMedGoogle Scholar
  26. 26.
    Parikh SV, Nagaraja HN, Hebert L, Rovin BH (2014) Renal flare as a predictor of incident and progressive CKD in patients with lupus nephritis. Clin J Am Soc Nephrol 9:279–284CrossRefPubMedGoogle Scholar
  27. 27.
    Pons-Estel BA, Catoggio LJ, Cardiel MH, Soriano ER, Gentiletti S, Villar AR, Grupo Latino americano de Estudio del Lupus et al (2004) The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics”. Medicine (Baltimore) 83:1–17CrossRefGoogle Scholar
  28. 28.
    Steiman AJ, Urowitz MB, Ibañez D, Papneja A, Gladman DD (2014) Prolonged clinical remission in patients with systemic lupus erythematosus. J Rheumatol 41(9):1808–1816CrossRefPubMedGoogle Scholar
  29. 29.
    Mok CC, Ho LY, Tse SM, Chan KL (2017) Prevalence of remission and its effect on damage and quality of life in Chinese patients with systemic lupus erythematosus. Ann Rheum Dis 76(8):1420–1425CrossRefPubMedGoogle Scholar
  30. 30.
    Zen M, Iaccarino L, Gatto M, Bettio S, Nalotto L, Ghirardello A, Punzi L, Doria A (2015) Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis 74:2117–2122CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Rudra Prosad Goswami
    • 1
  • Hiramanik Sit
    • 1
  • Parasar Ghosh
    • 1
  • Geetabali Sircar
    • 1
  • Alakendu Ghosh
    • 1
  1. 1.Department of RheumatologyInstitute of Post Graduate Medical Education and ResearchKolkataIndia

Personalised recommendations