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In RA, treatment with etanercept has a lower percentage of discontinuation than infliximab and adalimumab. Concomitant use of DMARDs, disease duration before treatment with a biologic and female sex predict time to discontinuation.

Objective. To analyze lipid changes in patients with rheumatoid arthritis (RA) and patients with spondyloarthritis (SpA) treated with biologic agents or tofacitinib in randomized clinical trials (RCTs).Methods. A systematic literature search was performed, using the Medline, Embase, Cochrane Library, and Web of Knowledge databases. Meta-analyses were performed using random-effects models to assess changes in the percentage of patients with abnormal lipid values or in the mean percentage of increase in the cholesterol and triglycerides levels.Results. Conclusion. In patients with RA treated with tocilizumab or tofacitinib but not with TNF antagonists, moderate changes in lipids are observed. Whether these changes pertain to the control of inflammation or to the mechanism of action of the biologic agents or tofacitinib remains undetermined.Rheumatoid arthritis (RA) and the spondyloarthritides (SpA) ankylosing spondylitis and psoriatic arthritis have an important impact on a patient's wellbeing, related partly to joint damage, disability, and poor quality of life but also to increased cardiovascular morbidity and mortality (1-3). The most important cause of death in RA and SpA is cardiovascular disease (4-6).

RCTs are not sensitive enough to assess the risk of reactivation of latent TB infection (LTBI). Disease, treatment and background TB rate are associated with different frequencies of active TB. The benefit/risk balance of preventing reactivation of LTBI in different backgrounds should be considered in clinical practice.

IMPORTANCE Knowledge of the immunogenicity of biologic agents may be helpful for the development of strategies for treatment of chronic immune-mediated inflammatory diseases. OBJECTIVE To summarize the influence of antibodies against biologic agents (AABs [seropositivity]) on efficacy and safety in immune-mediated inflammatory diseases. DATA SOURCES MEDLINE, EMBASE, Cochrane Library, and the Web of Knowledge were searched for articles published in English, Spanish, French, Italian, or Portuguese between 2000 and March 2012. The search strategy focused on synonyms of diseases, immunogenicity, and biologic agents. Abstracts from 2001 to 2011 of the European League Against Rheumatism and American College of Rheumatology congresses were also included. STUDY SELECTION The selection criteria were (1) observational or interventional studies in rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, spondyloarthritis, and psoriasis; (2) studies including patients who received biologic agents; and (3) studies collecting data on AABs. DATA EXTRACTION AND SYNTHESIS Data collected included publication details, study design, characteristics of patients and treatments, presence of antibodies, and definition of response. MAIN OUTCOMES AND MEASURES The primary end point was the association of AABs with response to treatment. Secondary end points were the association of AABs with safety, the association of AABs with concentration of the drug, and the influence of use of concomitant immunosuppressive therapy in the formation of AABs. RESULTS The search captured 10 728 articles and abstracts. By hand and reverse search, 31 articles were additionally included. After evaluation of the full reports, 60 references were selected. They included 59 studies of anti-tumor necrosis factor monoclonal antibodies: 1 with etanercept, 2 with rituximab, and 2 with abatacept. In rheumatoid arthritis but not in inflammatory bowel disease or spondyloarthritis, seropositive patients presented worse clinical response at 6 months or less (odds ratio [OR], 0.03; 95% CI, 0.01-0.21), and at 6 months or more (0.03; 0.00-0.30) by meta-analysis. In rheumatoid arthritis, discontinuation of the biologic agent for all reasons was more common in seropositive patients (OR, 3.53; 95% CI, 1.60-7.82). In all conditions, seropositive patients had a higher risk of hypersensitivity reactions (OR, 3.97; 95% CI, 2.36-6.67). Overall, concomitant treatment with disease-modifying antirheumatic drugs, including azathioprine, decreased the risk of seropositivity (OR, 0.32; 95% CI, 0.25-0.42). CONCLUSIONS AND RELEVANCE Presence of antibodies against anti-tumor necrosis factor monoclonal antibodies confers a risk of discontinuation of treatment in rheumatoid arthritis and a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases. The combined use of anti-tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks. Information on oth...

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ObjectiveTo identify predictors of response to tumor necrosis factor (TNF) antagonists in ankylosing spondylitis (AS) and psoriatic arthritis (PsA).MethodsSystematic review and meta-analysis of clinical trials and observational studies based on a systematic search. Meta-analyses of similar observations were performed using random effects computing summary OR. Heterogeneity was tested using I2, and risks of bias using funnel plots and the Egger test. Meta-regression was used to explore causes of heterogeneity.ResultsThe electronic search captured 1340 references and 217 abstracts. 17 additional articles were identified after searching by hand. A total of 59 articles meet the purpose of the study and were reviewed. 37 articles (33 studies) included 6736 patients with AS and 23 articles (22 studies) included 4034 patients with PsA. 1 article included data on AS and PsA. Age (OR (95% CI) 0.91 (0.84 to 0.99), I2=84.1%), gender (1.57 (1.10 to 2.25), I2=0.0%), baseline BASDAI (1.31 (1.09 to 1.57), I2=0.0%), baseline BASFI (0.86 (0.79 to 0.93), I2=24.9%), baseline dichotomous C reactive protein (CRP) (2.14 (1.71 to 2.68), I2=22.3%) and human leucocyte antigen B27 (HLA-B27) (1.81 (1.35 to 2.42), I2=0.0%) predict BASDAI50 response in AS. No factor was identified as a source of heterogeneity. Only meta-analysis of baseline BASFI showed risk of publication bias (Egger test, p=0.004). Similar results were found for ASAS criteria response. No predictors of response were identified in PsA.ConclusionsYoung age, male sex, high baseline BASDAI, low baseline BASFI, high baseline CRP and HLA-B27 predict better response to TNF antagonists in AS but not in PsA.

Event rates of serious infections and malignancies with PKi are not different from biologics. In addition, PKi have a unique safety profile related to target and off-target inhibition of kinases, at times dose related.