[en] Objectives: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. Methods: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. Results: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p< 0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. Conclusions: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.
Disciplines :
Rheumatology
Author, co-author :
Kirwan, J. R.
Hallgren, R.
Mielants, H.
Wollheim, F.
Bjorck, E.
Persson, T.
Book, C.
Bowman, S.
Byron, M.
Cox, N.
Field, M.
Kanerud, L.
Leirisalo-Repo, M.
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
Sheldon P. Rheumatoid arthritis and gut related lymphocytes: the iteropathy concept. Ann Rheum Dis 1988;47:697-700.
Porzio V, Biasi G, Corrado A, De Santi M, Vindigni C, Viti S, et al. Intestinal histological and ultrastructural inflammatory changes in spondyloarthropathy and rheumatoid arthritis. Scand J Rheumatol 1997;26:92-8.
Toivanen P. From reactive arthritis to rheumatoid arthritis. Autoimmunity 2001;16:369-71.
St Clair EW, Wilkinson WE, Pisetsky DS, Sexton DJ, Drew R, Kraus VB, et al. The effects of intravenous doxycycline therapy for rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2001;44:1043-7.
Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr 2000;83:207-17.
Muller H, de Toledo FW, Resch KL. Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review. Scand J Rheumatol 2001;30:1-10.
Mielants H, Veys EM, Cuvelier C, De Vos M. Course of gut inflammation in spondylarthropathies and therapeutic consequences. Baillieres Clin Rheumatol 1996;10:147-64.
Veys EM, Mielants H, De Vos M, Cuvelier C. Spondylarthropothies: from gut to target organs. Baillieres Clin Rheumatol 1996;10:123-46.
Gotzsche PC, Johansen HK. Short-term, low-dose corticosteroids and nonsteroidal anti-inflammatory drugs for rheumatoid arthritis. The Cochrane Library. Oxford: Update Software, 1999.
Saag KG, Criswell LA, Sems KM, Nettleman MD, Kolluri S. Low-dose corticosteroids in rheumatoid arthritis: a meta-analysis of their moderate-term effectiveness. Arthritis Rheum 1996;39:1818-25.
van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 2002 Jan 1;136:1-12.
Kirwan JR, ARC Low Dose Glucocorticoid Study Group. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 1995;333:142-6.
Edsbäcker S, Wollmer P, Nilsson A, Nilsson M. Pharmacokinetics and gastrointestinal transit of budesonide controlled ileal release (CIR) capsules [abstract]. Gastroenterology 1993;104:A695.
Edsbäcker S, Larsson P, Nilsson M, Wirén JE. Budesonide controlled ileal release (CIR) capsules affect plasma cortisol less than prednisolone [abstract]. Gastroenterology 1995;108(suppl 4):A814.
Danielsson Å, Hellers G, Lyrenäs E, Löfberg R, Nilsson Å, Olsson O, et al. A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Scand J Gastroenterol 1987;22:987-92.
Tarpila S, Turunen U, Seppälä K, Aukee S, Pikkarainen P, Elomaa I, et al. Budesonide enema in active haemorrhagic proctitis: a controlled trial against hydrocortisone foam enema. Aliment Pharmacol Ther 1994;8:591-5.
Rutgeerts P, Löfberg R, Malchow H, Lamers C, Olaison G, Jewell D, et al. A comparison of budesonide with prednisolone for active Crohn's disease. N Engl J Med 1994;331:842-5.
Östergaard Thomsen O, Cortot A, Jewell D, Wright JP, Winter T, Tavarela Veloso F, et al. A comparison of budesonide and mesalazine for active Crohn's disease (the international budesonide-mesalamine study group). N Engl J Med 1998;339:370-4.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
Steinbrocker O, Traegar CH, Batterman RC. Therapeutic criteria in rheumatoid arthritis. JAMA 1949;140.659-62.
Boers M, Tugwell P, Felson DT, van Riel PL, Kirwan JR, Edmonds JP, et al. World Health Organization and International League of Associations for Rheumatology core end points for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials. J Rheumatol 1994;21(suppl 41):86-9.
Fuchs HA, Brooks RH, Callahan L Pincus T. A simplified twenty-eight-joint quantitative articular index in rheumatoid arthritis. Arthritis Rheum 1989;32:531-7.
Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980;23:137-45.
MAPI Research Institute. Cultural adaption of the health assessment questionnaire (HAQ) into Belgian Dutch, Belgian French, Swedish and UK English. Report prepared by MAPI Research Institute, August 1998. Report on file, at AstraZeneca, Lund, Sweden.
Kirwan JR, Reeback JS. Stanford Health Assessment Questionnaire modified to assess disability in British patients with rheumatoid arthritis. Br J Rheumatol 1986;25:206-9.
Ware J, Sherbourne DC. The MOSS 36 item short-form health survey (SF-36). Med Care 1992;30:473-83.
Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35.
Edsbäcker S, Nilsson M, Larsson P. A cortisol suppression dose-response comparison of budesonide in controlled ileal release capsules with prednisolone. Aliment Pharmacol Ther 1999;13:219-24.
Criswell LA, Saag KG, Sems KM, Welch V, Shea B, Wells G, et al. Moderate-term, low-dose corticosteroids for rheumatoid arthritis (Cochrane review). The Cochrane Library, Issue 4. Oxford: Update Software, 2000.
Empire Rheumatism Council Subcommittee. Multi-Center controlled trial comparing cortisone acetate and acetyl salicylic acid in the long-term treatment of rheumatoid arthritis. Ann Rheum Dis 1955;14:353-63.
Harris E D, Emkey RD, Nichols JE, Newberg A. Low dose prednisone therapy in rheumatoid arthritis: a double blind study. J Rheumatol 1983;10:713-21.
Million R, Poole P, Kellgren, H, Jayson MIV. Long-term study management of rheumatoid arthritis. Lancet 1984;ii:812-16.
Stenberg VI, Fiechtner JJ, Rice JR, Miller DR, Johnson LK. Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical trial. Int J Clin Pharmacol Res 1992;12:11-18.
Van Gestel AM, Laan RFJM, Haagsma CJ, van de Putte LBA, van Riel PLCM. Low-dose oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold: a randomized double-blind placebo-controlled trial. Br J Rheumatol 1995;34:347-51.
Van Schaardenburg D, Valkema R, Dijkmans BAC, Papapoulos S, Zwinderman AH, Han KH, et al. Prednisone for elderly-onset rheumatoid arthritis: outcome and bone moss in comparison to treatment with chloroquine. Arthritis Rheum 1995;38:334-42.
Ritchie DM, Bayle JA, Mclnnes JM, Jasani MK, Dalakos T, Grieveson P, et al. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1968;147:393-406.