Challenges and opportunities in SLE clinical trials

Current Opinion in Rheumatology

Volumn 25, Issue 5, 2013, Pages 606-615

  Van Vollenhoven, Ronald F ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

clinical trials; endpoint; outcomes; systemic lupus erythematosus

Indexed keywords

ABATACEPT; ACETYLCYSTEINE; ATACICEPT; AZATHIOPRINE; BELIMUMAB; COLECALCIFEROL; CYCLOPHOSPHAMIDE; FORIGERIMOD; GLUCOCORTICOID; METHYLPREDNISOLONE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PIOGLITAZONE; PLACEBO; PREDNISONE; RITUXIMAB; TACROLIMUS;

CLINICAL TRIAL (TOPIC); DISEASE ACTIVITY; DRUG APPROVAL; DRUG MEGADOSE; DRUG SAFETY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FOOD AND DRUG ADMINISTRATION; HUMAN; LUPUS ERYTHEMATOSUS NEPHRITIS; PATIENT SELECTION; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PUBLICATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE ACTIVATION; TREATMENT DURATION; TREATMENT OUTCOME;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; HUMANS; IMMUNOCONJUGATES; IMMUNOSUPPRESSIVE AGENTS; LUPUS ERYTHEMATOSUS, SYSTEMIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH DESIGN; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84881535576     PISSN: 10408711     EISSN: 15316963     Source Type: Journal    
DOI: 10.1097/BOR.0b013e328363f4f2     Document Type: Review

References (52)

1. Petri MA, Lahita RG, Van Vollenhoven RF, et al. Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2002; 46:1820-1829.
2. Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009; 20:1103-1112.
3. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum 2010; 62:222-233.
4. Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis the lupus nephritis assessment with rituximab study. Arthritis Rheum-Us 2012; 64:1215-1226.
5. Merrill JT, Burgos-Vargas R, Westhovens R, et al. The efficacy and safety of abatacept in patients with nonlife-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2010; 62:3077-3087.
6. Furie R, Nicholls K, Cheng TT, et al. Efficacy and safety of abatacept over 12 months in patients with lupus nephritis: results from a multicenter, randomized, double-blind, placebo-controlled phase II/III study. Arthritis Rheum 2011; 63:S962-S963.
7. Navarra SV, Guzman RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377:721-731.
8. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 2011; 63:3918-3930.
9. Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum 2004; 50:2858-2868.
10. Cardiel MH, Tumlin JA, Furie RA, et al. Abetimus sodium for renal flare in systemic lupus erythematosus: results of a randomized, controlled phase III trial. Arthritis Rheum 2008; 58:2470-2480.
11. Kalunian KC, Davis JC Jr, Merrill JT, et al. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002; 46:3251-3258.
12. Boumpas DT, Furie R, Manzi S, et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum 2003; 48:719-727.
13. Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000; 343:1156-1162.
14. Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005; 353:2219-2228.
15. Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 2011; 365:1886-1895.
16. Houssiau FA, D'Cruz D, Sangle S, et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 2010; 69:2083-2089.
17. Stoenoiu MS, Aydin S, Tektonidou M, et al. Repeat kidney biopsies fail to detect differences between azathioprine and mycophenolate mofetil maintenance therapy for lupus nephritis: data from the MAINTAIN Nephritis Trial. Nephrol Dial Transplant 2012; 27:1924-1930.
18. Leandro MJ, Edwards JC, Cambridge G, et al. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum 2002; 46:2673-2677.
19. van Vollenhoven RF, Gunnarsson I, Welin-Henriksson E, et al. Biopsy-verified response of severe lupus nephritis to treatment with rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy-documented failure to respond to cyclophosphamide alone. Scand J Rheumatol 2004; 33:423-427.
20. Gunnarsson I, Sundelin B, Jonsdottir T, et al. Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide- resistant proliferative lupus nephritis. Arthritis Rheum 2007; 56:1263-1272.
21. van Vollenhoven RF. Rituximab: shadow, illusion or light? Autoimmun Rev 2012; 11:563-567.
22. Jonsdottir T, Zickert A, Sundelin B, et al. Long-term follow-up in lupus nephritis patients treated with rituximab: clinical and histopathological response. Rheumatology (Oxford) 2013.
23. Isenberg DA, Allen E, Farewell V, et al. An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA. Ann Rheum Dis 2011; 70:54-59.
24. Wofsy D, Hillson JL, Diamond B. Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum 2012; 64:3660-3665.
25. Petri M, Kasitanon N, Lee SS, et al. Systemic lupus international collaborating clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum 2008; 58:1784-1788.
26. Petri M, Kasitanon N, Singh S, et al. Systemic lupus international collaborating clinics renal activity/response exercise: comparison of agreement in rating renal response. Arthritis Rheum 2008; 58:1789-1795.
27. Finck BK, Linsley PS, Wofsy D. Treatment of murine lupus with CTLA4Ig. Science 1994; 265:1225-1227.
28. Wallace DJ, Stohl W, Furie RA, et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum 2009; 61:1168-1178.
29. van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis 2012; 71:1343-1349.
30. Manzi S, Sanchez-Guerrero J, Merrill JT, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis 2012; 71:1833-1838.
31. Stohl W, Hiepe F, Latinis KM, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum 2012; 64:2328-2337.
32. Wallace DJ, Navarra S, Petri MA, et al. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus 2013; 22:144-154.
33. Merrill JT, Ginzler EM, Wallace DJ, et al. Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Arthritis Rheum 2012; 64:3364-3373.
34. Dooley MA, Houssiau F, Aranow C, et al. Effect of belimumab treatment on renal outcomes: results from the phase 3 belimumab clinical trials in patients with SLE. Lupus 2013; 22:63-72.
35. Chatham WW, Wallace DJ, Stohl W, et al. Effect of belimumab on vaccine antigen antibodies to influenza, pneumococcal, and tetanus vaccines in patients with systemic lupus erythematosus in the BLISS-76 trial. J Rheumatol 2012; 39:1632-1640.
36. Strand V, Levy RA, Cervera R, et al. Improvements in health-related quality of life with belimumab, a B-lymphocyte stimulator-specific inhibitor, in patients with autoantibody-positive systemic lupus erythematosus from the randomised controlled BLISS trials. Ann Rheum Dis 2013; http://www.ncbi.nlm. nih.gov/pubmed/?term=strand+levy+cervera. [Epub ahead of print]
37. Lai ZW, Hanczko R, Bonilla E, et al. N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2012; 64:2937-2946.
38. Zimmer R, Scherbarth HR, Rillo OL, et al. Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebocontrolled phase IIb clinical trial. Ann Rheum Dis 2012. In a randomized controlled trial, Lupuzor was more effective than placebo, especially in patients with higher clinical disease activity.
39. Juarez-Rojas JG, Medina-Urrutia AX, Jorge-Galarza E, et al. Pioglitazone improves the cardiovascular profile in patients with uncomplicated systemic lupus erythematosus: a double-blind randomized clinical trial. Lupus 2012; 21:27-35.
40. Abou-Raya A, Abou-Raya S, Helmii M. The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. J Rheumatol 2013; 40:265-272.
41. Ginzler EM, Wax S, Rajeswaran A, et al. Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther 2012; 14:R33.
42. Sundel R, Solomons N, Lisk L, Study ALM. Efficacy of mycophenolate mofetil in adolescent patients with lupus nephritis: evidence from a two-phase, prospective randomized trial. Lupus 2012; 21:1433-1443.
43. Chen W, Liu Q, Tang X, et al. Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 2012; 21:944-952.
44. Arends S, Grootscholten C, Derksen RH, et al. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis. Ann Rheum Dis 2012; 71:966-973.
45. Miossi R, Benatti FB, Luciade de Sa Pinto A, et al. Using exercise training to counterbalance chronotropic incompetence and delayed heart rate recovery in systemic lupus erythematosus: a randomized trial. Arthritis Care Res (Hoboken) 2012; 64:1159-1166.
46. Davies RJ, Lomer MC, Yeo SI, et al. Weight loss and improvements in fatigue in systemic lupus erythematosus: a controlled trial of a low glycaemic index diet versus a calorie restricted diet in patients treated with corticosteroids. Lupus 2012; 21:649-655.
47. Bello KJ, Fang H, Magder LS, Petri M. Increase in vitamin D improves disease activity and systolic blood pressure in systemic lupus erythematosus. Arthritis Rheum-Us 2012; 64:S732-S733.
48. Aranow C, Dall'Era M, Massarotti EM, et al. A double-blind randomized placebo-controlled trial of the effect of vitamin D3 on the interferon signature in patients with systemic lupus erythematosus. Arthritis Rheum 2012; 64:S1110-S1120.
49. Oswald M, Aranow C, Kamen DL, et al. Modular microarray analysis fails to reveal a significant biological effect of vitamin D3 treatment in patients participating in a double-blind randomized placebo-controlled trial of the effect of vitamin D3 on the interferon signature in patients with systemic lupus erythematosus. Arthritis Rheum 2012; 64:S1139-S1140.
50. Boumpas DT, Austin HA, Vaughn EM, et al. Controlled trial of pulse methylprednisolone versus 2 regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992; 340:741-745.
51. Esdaile J. A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus-erythematosus.NewEngl JMed1991;324:150-154.
52. Houssiau FA, Vasconcelos C, D'Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002; 46:2121-2131.