Seven-year follow-up of infliximab therapy in rheumatoid arthritis patients with severe long-standing refractory disease: attrition rate and evolution of disease activity.
BACKGROUND
This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation.


METHODS
Between 2000 and 2001, 511 patients with severe and refractory RA were enrolled and treated with infliximab. After 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.


RESULTS
After 7 years, 160 of 511 patients (31%) were still on infliximab treatment. The major reasons for infliximab discontinuation included lack of efficacy (104 patients), adverse events (107 patients) and elective change of therapy (70 patients). The majority of cases of treatment discontinuation for safety reasons occurred during the first 2 years. In contrast, discontinuation due to ineffectiveness showed a more constant rate over the 7-year period. Mean DAS for patients still on treatment with infliximab decreased from 5.7 (standard error [SE] 0.1) at baseline to 3.0 (SE 0.1) at year 4 and remained that low until year 7 (3.0 [SE 0.1]). Low disease activity (defined as DAS28<3.2) was present in 60.9% of patients, and 45.5% achieved remission (DAS28<2.6). DAS28 at the time of treatment discontinuation due to ineffectiveness decreased over the 7-year period from 5.6 (SE 0.3) in 2001 to 4.8 (SE 0.3) in 2008.


CONCLUSIONS
This observational study revealed that patients who continue to receive infliximab experience sustained clinical benefit. The majority of safety issues occurred during the first 2 years of infliximab therapy. We observed that the DAS at the time of therapy discontinuation showed a trend to decrease over time.
Vander Cruyssen
Bert
B
Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Bert.VanderCruyssen@Ugent.be
Durez
Patrick
P
Westhovens
Rene
R
De Keyser
Filip
F
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001530:Belgium; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006306:Health Surveys; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab; D008727:Methotrexate
Arthritis Res Ther. 2005;7(5):R1063-71
16207323
Arthritis Rheum. 1980 Feb;23(2):137-45
7362664
Ann Rheum Dis. 2003 Oct;62(10):944-51
12972472
Ann Rheum Dis. 2008 Jul;67(7):1023-6
18272669
Arthritis Rheum. 1995 Jan;38(1):44-8
7818570
Arthritis Rheum. 2010 Jan;62(1):22-32
20039405
N Engl J Med. 2000 Nov 30;343(22):1594-602
11096166
J Rheumatol. 1993 Mar;20(3):579-81
8478878
Arthritis Rheum. 2005 Sep;52(9):2616-24
16142762
Rheumatology (Oxford). 2005 Apr;44(4):465-8
15695306
Ann Rheum Dis. 2008 Sep;67(9):1229-34
18174220
Rheumatology (Oxford). 2007 Mar;46(3):529-32
17012439
Arthritis Res Ther. 2006;8(4):R112
16978395
Arthritis Res Ther. 2006;8(3):R72
16620398
Ann Rheum Dis. 2006 Jun;65(6):753-9
16308341
Lancet. 1999 Dec 4;354(9194):1932-9
10622295
Am J Med. 2005 May;118(5):515-20
15866254