Blood Lymphocyte Subsets for Early Identification of Non-Remission to TNF Inhibitors in Rheumatoid Arthritis.

Background: TNF inhibitors (TNFis) are widely used for the treatment of rheumatoid arthritis (RA), although the response rates to this therapy in patients with RA remains heterogeneous and < 50% achieve remission (REM). Objective: To analyze baseline peripheral blood leukocytes profiles in order to search for biomarkers identifying patients who will most likely not achieve REM under TNFi treatment. Methods: A prospective bi-center pilot study including 98 RA patients treated with TNFis and followed-up during 6 months. Patients were classified according to DAS28 as follows: those who achieved REM (DAS28 ≤ 2.6) and those who did not (DAS28 > 2.6) at 6 months after starting TNFis. These rates were also assessed by simplified disease activity index (SDAI ≤ 3.3 and SDAI > 3.3, respectively). Peripheral blood immune cells were studied by flow cytometry before treatment initiation. Results: At 6 months, 61 or 80% of patients did not achieve REM by DAS28 or SDAI, respectively. Basal leukocyte profiles differed between REM vs. non-REM patients. Non-REM patients showed lower percentages of total and naïve B cells at baseline than REM subjects. A B lymphocyte/CD4+ lymphocyte ratio (BL/CD4 ratio) <0.2 clearly associated with a higher probability of non-REM status based on DAS28 at 6 months (OR = 9.2, p = 0.006). These data were confirmed when patient response was evaluated by SDAI index. Conclusion: Our results strongly suggest that BL/CD4 ratio could be considered as a useful biomarker for the early identification of non-remitters to TNFi in clinical practice.

Diagnostic concordance between primary care physicians and rheumatologists in patients with work disability related to musculoskeletal disorders.

To assess the diagnostic correlation between primary care physicians and rheumatologists in patients with temporary work disability (TWD) related to musculoskeletal diseases (MSD). All patients with TWD related to MSDs in three health districts of Madrid, Spain, were randomized into standard care by primary care physicians (PCP) or the intervention group by rheumatologists. According to the cause, every TWD episode was classified into 11 syndrome categories. To examine the concordance between the rheumatologist and the referring PCP for each diagnosis, we used Kappa statistic (k) and 95% confidence interval (CI). A total of 3,311 (62.8%) were analyzed, 49.8% women, with a mean age of 41 years ± 12 years, 93.3% were general workers. The agreement between PCP and rheumatologists in all the diagnoses was moderated (k = 0.62). The highest agreement was found in tendonitis (k = 0.81, 95% CI 0.78-0.84), and microcrystalline and undifferentiated arthritis (k = 0.72, 95% CI 0.68-0.77). Lowest agreements were found for peripheral osteoarthritis (k = 0. 48 95% CI 0.38-0.57), knee pain (k = 0.40, 95% CI 0.29-0.52), and muscular pain (k = 0.15, 95% CI 0.10-0.20) Although the global agreement on the musculoskeletal diagnosis between PCPs and rheumatologist in patients with TWD related to MSDs was reasonable, the correlation for peripheral osteoarthritis, knee pain, and muscular pain was low.

A health system program to reduce work disability related to musculoskeletal disorders.

BACKGROUND: Musculoskeletal disorders (MSDs) are a frequent cause of work disability, accounting for productivity losses in industrialized societies equivalent to 1.3% of the U.S. gross national product. OBJECTIVE: To evaluate whether a population-based clinical program offered to patients with recent-onset work disability caused by MSDs is cost-effective. DESIGN: Randomized, controlled intervention study. The inclusion and follow-up periods each lasted 12 months. SETTING: Three health districts in Madrid, Spain. PATIENTS: All patients with MSD-related temporary work disability in 1998 and 1999. INTERVENTION: The control group received standard primary care management, with referral to specialized care if needed. The intervention group received a specific program, administered by rheumatologists, in which care was delivered during regular visits and included 3 main elements: education, protocol-based clinical management, and administrative duties. MEASUREMENTS: Efficacy variables were 1) days of temporary work disability and 2) number of patients with permanent work disability. All analyses were done on an intention-to-treat basis. RESULTS: 1,077 patients were included in the study, 7805 in the control group and 5272 in the intervention group, generating 16,297 episodes of MSD-related temporary work disability. These episodes were shorter in the intervention group than in the control group (mean, 26 days compared with 41 days; P < 0.001), and the groups had similar numbers of episodes per patient. Fewer patients received long-term disability compensation in the intervention group (n = 38 [0.7%]) than in the control group (n = 99 [1.3%]) (P < 0.005). Direct and indirect costs were lower in the intervention group than in the control group. To save 1 day of temporary work disability, 6.00 dollars had to be invested in the program. Each dollar invested generated a benefit of 11.00 dollars. The program's net benefit was in excess of 5 million dollars. LIMITATIONS: The study was unblinded. CONCLUSIONS: Implementation of the program, offered to the general population, improves short- and long-term work disability outcomes and is cost-effective.