Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab.

Rheumazentrum Ruhrgebiet, Herne, Germany.
Arthritis research & therapy (Impact Factor: 4.12). 01/2005; 7(3):R439-44. DOI: 10.1186/ar1693
Source: PubMed Central

ABSTRACT We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value >or= 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment >or= 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 +/- 1.7 and that in the physician's global assessment was 4.4 +/- 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (+/- 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.

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    ABSTRACT: OBJECTIVE: To investigate whether biologic-free remission can be achieved in patients with early, active axial spondyloarthritis (SpA) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen (NPX) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control. METHOD: Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) Part 1 was a double-blind, randomised, controlled trial in biologic-naïve patients with early, active, moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks. Patients achieving Assessment of SpondyloArthritis international Society (ASAS) partial remission at week 28 continued to Part 2 and were randomised (1:1) to NPX or no treatment until week 52. Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests. RESULTS: At week 52, similar percentages of patients in the NPX group (47.5%, 19/40) and the no-treatment group (40.0%, 16/40) maintained partial remission, p=0.65. Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group (p=0.38). Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28, the start of follow-up treatment (NPX, 0.7; no treatment, 0.6), and remained low at week 52 (NPX, 1.2; no treatment, 1.7). CONCLUSIONS: In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone, disease activity remained low, and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped.
    Annals of the rheumatic diseases 06/2013; · 9.27 Impact Factor
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    ABSTRACT: The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial spondyloarthritis and established ankylosing spondylitis. In axial spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals. Axial spondyloarthritis (axSpA) is an inflammatory dis-ease of the axial skeleton and pelvis. Regardless of whether it progresses onto ankylosing spondylitis (AS), axSpA has an appreciable disease burden. axSpA is also associated with co-morbidities such as uveitis, psoriasis, inflammatory bowel disease, cardiovascular disease, osteoporosis and significant loss of work productivity. There is emerging evidence that early treatment may change the outcome in axSpA. The window of opportunity is a concept of critical im-portance in rheumatoid arthritis (RA). Early treatment results in reductions of disease activity, joint erosions, and better treatment responses the earlier disease-modifying anti-rheumatic drugs are commenced. It also results in a greater proportion of patients in drug-free remission after treatment withdrawal. These findings have led to changes in RA treatment paradigms, with in-creasing emphasis on early diagnosis and treatment. So how is this concept relevant to axSpA? A number of studies have demonstrated early treatment that
    Arthritis Research & Therapy 05/2014; 16:109. · 4.12 Impact Factor
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    ABSTRACT: IntroductionBiomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick ¿go/no go¿ decisions in the clinical development of new treatments. We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials.Methods The candidate biomarkers high sensitive-C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay in healthy controls (n¿=¿20) and SpA patients before and after 2 weeks of infliximab (n¿=¿18) or placebo (n¿=¿19) treatment in cohort 1. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2, n¿=¿21) and peripheral SpA with etanercept (cohort 3, n¿=¿20).ResultsSerum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P¿<¿0.001) and MMP-3 (P¿=¿0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (P¿<¿0.001) and hs-CRP (P¿<¿0.001) levels, with a similar trend for MMP-3 (P¿=¿0.063). The standardized response mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin.(¿1.26), good for hs-CRP (¿0.96) and moderate for MMP-3 (¿0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as evaluated and confirmed in cohort 2 and 3 respectively.Conclusions Calprotectin and hs-CRP are good serum biomarkers with high sensitivity to change upon effective treatment at the group level in small-scale, short term PoC trials in SpA.
    Annals of the Rheumatic Diseases 08/2014; 16(5):413. · 9.27 Impact Factor

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