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OBJECTIVE: Rheumatoid arthritis is a risk factor for tuberculosis (TB), particularly following treatment with biologic agents. Since these therapies are increasingly used in ankylosing spondylitis (AS), other types of spondyloarthritis (SpA), and psoriatic arthritis (PsA), we investigated the corresponding TB risks in these patients. METHODS: We identified individuals with AS/SpA/PsA, and non-AS/SpA/PsA comparators by linking Swedish national patient, population, TB, and rheumatology registers, and followed them for TB occurrence. Incidence rates were estimated for biologic-naive and biologic-exposed patients and the comparators. We calculated hazard ratios (HRs), adjusted for age, sex, and country of birth. RESULTS: Included in this study were 38,702 patients with AS/SpA/PsA, and 200,417 persons from the general population. Among the patients, 11 active TB cases were identified, with an incidence rate (per 105 ) of 22 (95% confidence interval [95% CI] 8.3-59.2) for biologic-exposed patients, 2.7 (95% CI 1.3-5.6) for biologic-naive patients, and 2.4 (95% CI 1.8-3.3) for non-AS/SpA/PsA comparators. The adjusted HR comparing biologic-naive patients to the general population was 1.2 (95% CI 0.5-2.7), and 7.5 (95% CI 1.9-29) comparing biologic-exposed to biologic-naive patients. CONCLUSION: Biologic-naive AS/SpA/PsA patients are not at an increased TB risk in Sweden. Following treatment with biologic agents, the risk increased, but the absolute TB risk was low.

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OBJECTIVES: C-reactive protein (CRP) levels are frequently used to determine disease activity in patients with ankylosing spondylitis (AS), but these levels may not reflect disease activity. We therefore investigated the influence of common single-nucleotide polymorphisms (SNPs) in the CRP gene on CRP levels in AS patients. Additionally, the relation between CRP levels and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) was examined. METHODS: This exploratory cross-sectional study included 189 Dutch AS patients. CRP SNPs rs2794521, rs3091244, rs1800947 and rs876538 were genotyped and haplotypes constructed. Linear regression analysis was used for the association between SNPs and CRP levels, with correction for confounders non-steroidal anti-inflammatory drugs use, body mass index, smoking, age, gender and disease activity (BASDAI). RESULTS: Only 52% of AS patients with a high disease activity (BASDAI ≥4) showed a high CRP level (≥10mg/L), whereas the others did not. In AS patients, CRP levels changed with different genotypes, with genotype CA of tri-allelic (C>T>A) SNP rs3091244 showing higher CRP levels in comparison with genotype CC (CA: 18.6 mg/L vs. CC: 8.3 mg/L; p=0.02). Carriers of haplotype 5 (tagged by allele A of rs3091244) had a higher risk to express a CRP ≥10 mg/L (OR=2.9, 95%CI 1.0-8.3; p=0.05) when compared with non-carriers. CONCLUSIONS: In AS, patients with high disease activity often do not show corresponding high CRP levels. We found that CRP levels vary with different CRP genotype in AS patients. Carrying distinct genetic variants might play a role in certain AS patients who show low CRP levels despite high disease activity (as well as high CRP levels with low disease activity). This observation may be important for the interpretation of disease activity scores that incorporate CRP levels, like the ASDAS.

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The objective of this study is to investigate the prevalence of Andersson lesions (AL) in ankylosing spondylitis (AS) patients who will start anti-tumor necrosis factor (TNF) treatment. Radiographs and magnetic resonance imaging (MRI) of the spine were performed before therapy with anti-TNF. ALs were defined as discovertebral endplate destructions on MRI, associated with bone marrow edema and fat replacement or sclerosis, a decreased signal on T1, enhancement after contrast administration (gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)), and increased signal on T2 and short tau inversion recovery (STIR). Additionally, conventional radiography showed a fracture line, irregular endplates, and increased sclerosis of adjacent vertebral bodies. Fifty-six AS patients were included, 68% males, mean age of 43 years, and mean disease duration of 11 years. The mean bath ankylosing spondylitis disease activity index was 6.4, and 24% of all patients had ankylosis. Only one patient showed a discovertebral abnormality with bone marrow edema of more than 50% of the vertebral bodies adjacent to the intervertebral disk of T7/T8 and T9/T10, a hypodense signal area on T1, and a high signal on STIR. Irregular endplates were depicted, and T1 after Gd-DTPA demonstrated high signal intensity around the disk margins. However, no fracture line was visible on conventional radiology, and therefore, this case was not considered to be an AL. No AL was detected in our AS patients, who were candidates for anti-TNF treatment. One patient showed a discovertebral abnormality on MRI, without a fracture line on conventional radiology. The relative small proportion of patients with a long-established disease might explain this finding for, particularly, an ankylosed spine is prone to develop an AL.

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OBJECTIVE: To study the usefulness of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum amyloid A (SAA) for response prediction and monitoring of anti-tumor necrosis factor (anti-TNF) treatment in ankylosing spondylitis (AS) patients. METHODS: Patients were included consecutively before starting etanercept or infliximab treatment. ASsessment in Ankylosing Spondylitis (ASAS) response, defined as a 50% improvement or an absolute improvement of 2 points of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; 0-10 scale), was assessed at 3 months. Inflammatory markers and the BASDAI were collected at baseline and 1 and 3 months. Longitudinal data analysis was performed to compare associations between inflammatory markers and the BASDAI over time by calculating standardized betas. Predictive values of baseline levels of inflammatory markers for ASAS response were calculated. RESULTS: In total, 155 patients were included, of whom, after 3 months of treatment, 70% in the etanercept cohort and 71% in the infliximab cohort responded. All markers, notably SAA, decreased significantly (P < 0.0001). Standardized betas were 0.49 for ESR, 0.43 for CRP, and 0.39 for SAA. Normal baseline levels of CRP and SAA were significantly associated with nonresponse. A combination of elevated CRP and SAA levels at baseline revealed the highest predictive value (81%) for ASAS response. CONCLUSION: ESR, CRP, and SAA were significantly associated with the BASDAI over 3 months, and the association with ESR was the strongest. Elevated baseline CRP and SAA levels revealed the highest predictive value for response. Together, this study demonstrates that inflammatory markers, and notably CRP and SAA, may facilitate patient selection and monitoring of efficacy of anti-TNF treatment in AS, and could be added to response criteria.

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A well-known complication in patients with ankylosing spondylitis (AS) is the development of localised vertebral or discovertebral lesions of the spine, which was first described by Andersson in 1937. Since then, many different terms are used in literature to refer to these localised lesions of the spine, including the eponym 'Andersson lesion' (AL). The use of different terms reflects an ongoing debate on the exact aetiology of the AL. In the current study, we performed an extensive review of the literature in order to align communication on aetiology, diagnosis and management between treating physicians. AL may result from inflammation or (stress-) fractures of the complete ankylosed spine. There is no evidence for an infectious origin. Regardless of the exact aetiology, a final common pathway exists, in which mechanical stresses prevent the lesion from fusion and provoke the development of pseudarthrosis. The diagnosis of AL is established on conventional radiography, but computed tomography and magnetic resonance imaging both provide additional information. There is no indication for a diagnostic biopsy. Surgical instrumentation and fusion is considered the principle management in symptomatic AL that fails to resolve from a conservative treatment. We advise to use the term Andersson lesion for these spinal lesions in patients with AS.

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OBJECTIVES: Correlation of serum trough infliximab levels and antibodies to infliximab (anti-infliximab) with clinical response in ankylosing spondylitis. METHODS: In accordance with the international ASsessment in Ankylosing Spondylitis (ASAS) consensus statement, patients were treated with infliximab (5 mg/kg) every 6 weeks after a starting regimen. Preinfusion sera were collected at baseline, 24 and 54 weeks. At every visit, the 20% improvement response (ASAS-20) was assessed and laboratory tests performed. RESULTS: 24 of the 38 (63%) patients fulfilled ASAS-20 response criteria after 24 weeks of treatment and 21 (53%) after 54 weeks. After 54 weeks, 11 (29%) patients showed undetectable serum trough infliximab levels and detectable anti-infliximab; six of these patients developed an infusion reaction. Anti-infliximab was found significantly more often (p = 0.04) in ASAS-20 non-responders compared with responders at week 54. Serum trough infliximab levels were significantly (p<0.0001) lower in patients with (mean 0.02 mg/l) than in those without (12.7 mg/l) anti-infliximab. CONCLUSIONS: In ankylosing spondylitis, high levels of serum trough infliximab correlated with a good clinical response. Detection of anti-infliximab within 54 weeks is associated with undetectable serum trough infliximab levels, reduced response to treatment and increased risk of developing an infusion reaction.

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