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Objectives: To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib., Methods: Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05)., Results: We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15-161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36))., Conclusions: Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To determine the rate and factors associated with ankylosing spondylitis in a cohort of patients with undifferentiated spondyloarthritides (SpA)., Methods: 62 consecutive patients with undifferentiated SpA seen between 1998 and 1999 underwent clinical and imaging evaluations throughout follow up. The main outcome measure was a diagnosis of ankylosing spondylitis., Results: 50 patients with peripheral arthritis (n = 35) and inflammatory back pain (n = 24) (26 male; mean (SD) age at onset, 20.4 (8.8) years; disease duration 5.4 (5.7) years) were followed up for 3-5 years. At baseline, >90% of patients had axial and peripheral disease, while 38% had radiographic sacroiliitis below the cut off level for a diagnosis of ankylosing spondylitis (BASDAI 3.9, BASFI 2.9). At the most recent evaluation, 21 patients (42%) had ankylosing spondylitis. Two factors were associated with a diagnosis of ankylosing spondylitis in multivariate analysis: radiographic sacroiliitis grade <2 bilateral, or grade <3 unilateral (odds ratio (OR) = 11.18 (95% confidence interval, 2.59 to 48.16), p = 0.001), particularly grade 1 bilateral (OR = 12.58 (1.33 to 119.09), p = 0.027), and previous uveitis (OR = 19.25 (1.72 to 214.39), p = 0.001). Acute phase reactant levels, juvenile onset, and HLA-B27 showed a trend to linkage with ankylosing spondylitis (NS)., Conclusions: Low grade radiographic sacroiliitis is a prognostic factor for ankylosing spondylitis in patients originally classified as having undifferentiated SpA. Low grade radiographic sacroiliitis should be regarded as indicative of early ankylosing spondylitis in patients with undifferentiated SpA.

Objective: To investigate the role of HLA-B and HLA-DR genes as contributors to genetic susceptibility and clinical expression of the spondyloarthropathies (SpA) in the Mexican population., Methods: The study included 172 patients with SpA (undifferentiated SpA 83, ankylosing spondylitis (AS) 64, and reactive arthritis 25) and 99 healthy controls. The HLA-B and HLA-DR alleles were detected by the polymerase chain reaction with sequence-specific primers technique. Patient assessment included demographic data, diagnostic categories, and disease patterns. Statistical methods included the Mantel-Haenzel chi(2) test, Fisher's exact test, and Woolf method for odds ratio (OR). Differences of continuous variables between HLA allele groups were calculated by Student's t test., Results: Increased frequencies of HLA-B27 (pCh10(-3), OR=28.7), HLA-DR1 (pC=0.045, OR=2.77), and HLA-B15 (p=0.034, pC=NS, OR=2.04) alleles in the whole group were found. HLA-B27 strength of association (OR) was 41.4 in AS; 20.9 in undifferentiated SpA; 27.2 in reactive arthritis. HLA-DR1 and HLA-B15 were increased in undifferentiated SpA (pC=0.045, OR=2.98 and p=0.004, pC=NS, OR=2.75). By analysing 58 HLA-B27 negative patients it was found that HLA-B15 and HLA-DR1 associations with SpA were independent of HLA-B27; increased frequencies of HLA-B15 were found in the whole SpA group and in patients with undifferentiated SpA (pC=0.03, OR=3.09 and pCh0.01, OR=3.77) and of HLA-DR1 in the latter (p=0.04, pC=NS, OR=3.15). HLA-B27 positive patients were younger than HLA-B27 negative patients at onset (p=0.03), but HLA-DR1 positive patients were older than HLA-DR1 negative patients (p=0.03). Bath indices for disease activity and functioning were higher in HLA-B27 positive patients (p=0.006 and p=0.004 v HLA-B27 negative patients). In contrast, neither HLA-DR1 nor HLA-B15 influenced these indices., Conclusion: Apart from HLA-B27, there is a significant association of HLA-DR1 and HLA-B15 with SpA in Mexicans which is independent of B27. HLA-B27 is associated with younger age at onset and increased disease severity and HLA-DR1 with older age at onset. The strength of HLA-B15, HLA-B27, and HLA-DR1 associations varied in different forms of SpA.

Objective: To develop and test an index to evaluate the radiographic changes that occur in the tarsus and adjacent areas of the foot in patients with spondyloarthropathies (SpA)., Methods: The spondyloarthropathy tarsal radiographic index (SpA-TRI) was developed in three consecutive steps: (a) detection of descriptors after reviewing 70 radiographic files; (b) descriptor gradation and subsequent modifications performed by a consensus committee, and (c) interobserver variability assessed by three blinded and independent observers on 272 radiographs: anteroposterior 118, lateral 90, oblique 64 from 121 patients with SpA, and intraobserver variability on 75 radiographs from 25 patients with SpA. Statistical analysis included percentage of agreement and kappa test. SpA-TRI score ranges from 0 to 4 (0=normal; 1=osteopenia or suspicious findings; 2=definite joint space narrowing, bony erosion(s), periosteal whiskering, or enthesophyte(s) in the plantar fascia or Achilleal tendon attachments; 3=para-articular enthesophyte(s); 4=bony ankylosis (joint space fusion or complete bridging))., Results: Complete agreement for every evaluation was >40%, and discordance >1 grade was <15%. The kappa scores among the three observers were acceptable for all the single projections: oblique (0.52, 0.36, 0.35), lateral (0.50, 0.42, 0.56), and anteroposterior (0.40, 0.41, 0.21) views. The combination of lateral and oblique views achieved the highest concordance rates (0.72, 0.33, 0.66), surpassing that of the three projections altogether (0.34, 0.58, 0.37). In every case the concordance was comparable with that of sacroiliac joints (0.47, 0.41, 0.34); intraobserver concordance showed a similar trend., Conclusion: The SpA-TRI is an index that includes the most prominent features of tarsal disease and adjacent areas of the foot in SpA and grades them accordingly, it has an adequate reproducibility, and is suitable for use with two or more projections, preferably the combination of oblique and lateral.

Objective: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population., Methods: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, chi(2), Fisher's exact test, and Woolf's method for odds ratio (OR)., Results: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC<0.05, OR=4.3), as well as in the different clinical subgroups (pC<0.05, OR=4.2 for AS; pC<0.05, OR=4.4 for uSpA; and pC<0.05, OR=4.1 for ReA). This frequency remained significantly increased when the patients with B27 negative SpA were analysed. On the other hand, HSP70-hom locus analysis showed significantly increased frequency of A allele in the whole group of SpA (pC<0.05, OR=3.4), as well as in the groups with AS (pC<0.05, OR=5.6) and with uSpA (pC<0.05, OR=3.1), when compared with healthy controls. In this case, also, the genotype A/A was increased in the whole group of SpA (pC<0.05, OR=4.5), as well as in patients with AS (pC<0.05, OR=6.4) and with uSpA (pC<0.05, OR=3.7). When the patients with B27 negative SpA were analysed the frequencies of HSP70-hom A allele and A/A genotype remained significantly increased in the whole group of SpA (pC<0.05, OR=3.2 for the A allele and pC<0.05, OR=4.2 for the A/A genotype) and in the uSpA subgroup (pC<0.05, OR=3.8 for the A allele and pC<0.05, OR=4.3 for the A/A genotype)., Conclusion: In addition to the association of SpA with HLA-B27, there is a significant association of HSP70-2 and HSP70-hom alleles with SpA in Mexicans. This association seems to be independent of the susceptibility conferred by HLA-B27 in the group of patients with uSpA.