This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.
Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30–40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty syndrome patients who were monitored at the rheumatology outpatient clinic for Felty syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two syndromes is warranted.
Objective
Frequent monitoring of patients with early rheumatoid arthritis (RA) is required for achieving good outcomes. This study was undertaken to investigate the influence of text message (SMS)–enhanced monitoring on early RA outcomes.
Methods
We randomized 166 patients with early, disease‐modifying antirheumatic drug–naive RA to receive SMS‐enhanced follow‐up or routine care. All patients attended visits at 0, 3, and 6 months, and a follow‐up visit at 12 months. Treatment was at the physicians’ discretion. The intervention included 13 SMSs during weeks 0–24 with questions concerning medication problems (yes/no) and disease activity (patient global assessment [PtGA], scale 0–10). Patients were contacted if response SMSs indicated medication problems or PtGA exceeded predefined thresholds. Primary outcome was 6‐month Boolean remission (no swollen or tender joints and normal C‐reactive protein levels). Quality of life (QoL; measured by the Short Form 36 survey) and Disease Activity Score in 28 joints (DAS28) were assessed.
Results
Six and 12‐month follow‐up data were available for 162 and 157 patients, respectively. In the intervention group, 46% of the patients (38 of 82) reported medication problems and 49% (40 of 82) reported text message PtGAs above the alarm limit. Remission rates at 6 months (P = 0.34) were 51% in the intervention group and 42% in the control group. These rates were 57% and 43% at 12 months (P = 0.17) in the intervention and control groups, respectively. The respective mean ± SD DAS28 scores for the intervention and control groups were 1.92 ± 1.12 and 2.22 ± 1.11 at 6 months (P = 0.09); and 1.79 ± 0.91 and 2.08 ± 1.22 at 12 months (P = 0.28). No differences in QoL were observed.
Conclusion
The study did not meet the primary outcome despite a trend favoring the intervention group. This may be explained by the notably high overall remission rates.
Only a small proportion of patients would have been eligible for RCTs, and the efficacy of TNF inhibitors assessed in them cannot be generalized directly into Finnish routine health care.
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