ASAS/EULAR Management of Ankylosing Spondylitis
Objective. To perform a literature review as basis for the update of the Assessment in SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) treatment recommendations with biologics in AS.
Methods. A literature search of all publications found in MedLine, Embase and Cochrane database between 2005 and 2009 and in the EULAR/ACR meetings between 2007 and 2009 was performed. The research evidence and strength of recommendation (SOR) for biologics were provided.
Results. Out of 247 reports on AS treatment with biologics, 98 contained efficacy data and 25 had complete data for analysis. The treatment effect sizes (95% CI) for anti-TNF vs placebo varied between 0.34 (0.08, 0.6) and 1.5 (0.45, 2.5) for BASDAI and 0.33 (0.07, 0.59) and 2.5 (1.3, 3.7) for BASFI. The calculation of the numbers needed to treat all the different outcomes varied between 2.3 and 3.0 patients for all ASAS outcomes and between 2.7 and 6.5 patients for ASAS partial remission. Data on biologics other than anti-TNF and for TNF blockers on juvenile SpA were limited. The incidence rates of uveitis during anti-TNF treatment varied between 4.4/100 patient-years (pys) and 15.6/100 pys during placebo (P < 0.05). The incidence rates of IBD flares were significantly less during infliximab treatment (0.2/100 pys). The rate of infections was higher in patients treated with anti-TNF as compared with placebo, but there was no difference in the incidence of serious infections for treatment with anti-TNF vs placebo.
Conclusions. The overall evidence was very high for anti-TNF treatment (1b, SOR: A) with respect to efficacy and safety, while it was low for biologic treatment other than anti-TNF (3, SOR: C).
Treatment with anti-TNF has shown short- and long-term efficacy without major safety issues in clinical trials of patients with active AS. At the moment, four different anti-TNF agents are available and approved for the treatment of AS (infliximab, etanercept, adalimumab and golimumab). In 2003, the Assessment in SpondyloArthritis international Society (ASAS) proposed recommendations for the use of anti-TNF agents in patients with AS, based on a Delphi questionnaire, published data, clinical expertise and a consensus meeting among experts. In 2006, the ASAS/European League Against Rheumatism (EULAR) management recommendations of AS were published. These include guidance on non-pharmacological and pharmacological treatment including the use of TNF blockers. The recommendations for the use of anti-TNF agents and the ASAS/EULAR management recommendations are complimentary.
The recommendations for the use of anti-TNF agents were updated in 2006, since it was felt that the research had rapidly evolved in this area after the first publication. In the first update, several aspects of treatment with anti-TNF agents, such as the initiation, use and withdrawal of anti-TNF treatment, based on data on the efficacy and safety of those agents were taken into account. In 2009 it was decided that a second update of both the ASAS/EULAR recommendations for the management of AS and the recommendations for the use of anti-TNF agents should be performed. Two systematic literature reviews were performed to search for the underlying evidence: one on biologics and one on non-pharmacological and pharmacological (excluding biologics) treatment.
The primary outcome of interest for this systematic literature review was the evidence on the long-term efficacy and safety of TNF blockers in AS. This includes information on a possible distinction between the different TNF blockers, information about switching between TNF blockers in case of inefficacy or safety concerns, efficacy and safety of other biologics than TNF blockers and the efficacy of biologics including TNF blockers in patients fulfilling the ASAS classification criteria for axial SpA but not yet the modified New York criteria for AS.
Abstract and Introduction
Abstract
Objective. To perform a literature review as basis for the update of the Assessment in SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) treatment recommendations with biologics in AS.
Methods. A literature search of all publications found in MedLine, Embase and Cochrane database between 2005 and 2009 and in the EULAR/ACR meetings between 2007 and 2009 was performed. The research evidence and strength of recommendation (SOR) for biologics were provided.
Results. Out of 247 reports on AS treatment with biologics, 98 contained efficacy data and 25 had complete data for analysis. The treatment effect sizes (95% CI) for anti-TNF vs placebo varied between 0.34 (0.08, 0.6) and 1.5 (0.45, 2.5) for BASDAI and 0.33 (0.07, 0.59) and 2.5 (1.3, 3.7) for BASFI. The calculation of the numbers needed to treat all the different outcomes varied between 2.3 and 3.0 patients for all ASAS outcomes and between 2.7 and 6.5 patients for ASAS partial remission. Data on biologics other than anti-TNF and for TNF blockers on juvenile SpA were limited. The incidence rates of uveitis during anti-TNF treatment varied between 4.4/100 patient-years (pys) and 15.6/100 pys during placebo (P < 0.05). The incidence rates of IBD flares were significantly less during infliximab treatment (0.2/100 pys). The rate of infections was higher in patients treated with anti-TNF as compared with placebo, but there was no difference in the incidence of serious infections for treatment with anti-TNF vs placebo.
Conclusions. The overall evidence was very high for anti-TNF treatment (1b, SOR: A) with respect to efficacy and safety, while it was low for biologic treatment other than anti-TNF (3, SOR: C).
Introduction
Treatment with anti-TNF has shown short- and long-term efficacy without major safety issues in clinical trials of patients with active AS. At the moment, four different anti-TNF agents are available and approved for the treatment of AS (infliximab, etanercept, adalimumab and golimumab). In 2003, the Assessment in SpondyloArthritis international Society (ASAS) proposed recommendations for the use of anti-TNF agents in patients with AS, based on a Delphi questionnaire, published data, clinical expertise and a consensus meeting among experts. In 2006, the ASAS/European League Against Rheumatism (EULAR) management recommendations of AS were published. These include guidance on non-pharmacological and pharmacological treatment including the use of TNF blockers. The recommendations for the use of anti-TNF agents and the ASAS/EULAR management recommendations are complimentary.
The recommendations for the use of anti-TNF agents were updated in 2006, since it was felt that the research had rapidly evolved in this area after the first publication. In the first update, several aspects of treatment with anti-TNF agents, such as the initiation, use and withdrawal of anti-TNF treatment, based on data on the efficacy and safety of those agents were taken into account. In 2009 it was decided that a second update of both the ASAS/EULAR recommendations for the management of AS and the recommendations for the use of anti-TNF agents should be performed. Two systematic literature reviews were performed to search for the underlying evidence: one on biologics and one on non-pharmacological and pharmacological (excluding biologics) treatment.
The primary outcome of interest for this systematic literature review was the evidence on the long-term efficacy and safety of TNF blockers in AS. This includes information on a possible distinction between the different TNF blockers, information about switching between TNF blockers in case of inefficacy or safety concerns, efficacy and safety of other biologics than TNF blockers and the efficacy of biologics including TNF blockers in patients fulfilling the ASAS classification criteria for axial SpA but not yet the modified New York criteria for AS.