Gabriel Stavros Panayi

Lymphocyte Studies In Rheumatoid Arthritis Iii: A Comparative Study Of The Responses Of Peripheral Blood And Synovial Fluid Lymphocytes To Phytomitogens

The response of peripheral blood and synovial fluid lymphocytes to three non-specific mitogens has been studied. The paired samples were taken from patients with a range of inflammatory arthritides. Unstimulated synovial fluid lymphocytes (SFL) tended to have a greater uptake of tritiated thymidine than had unstimulated peripheral blood lymphocytes (PBL). This background uptake of tritiated thymidine by SFL showed a positive correlation with the response these SFL then showed to the mitogens. A significant depression was observed in the SFL response to phytohaemagglutinin when compared with the paired PBL response; this was seen in both the rheumatoid arthritis and other inflammatory joint diseases groups. SFL responses to concanavalin A and pokeweed mitogen, although depressed in individual cases, failed to show a significant depression overall. Attempts to restore the SFL response to that of the paired PBL by removal of any possible blocking substance from the cell surface either by pre-incubation of SFL in tissue culture medium or by enzyme treatment were unsuccessful. This suggested that cell surface blockers were possibly not the reason for deficient SFL reponses and that other factors were involved.

Goal-directed therapy for RA in routine practice is associated with improved function in patients with disease duration up to 15 years

Sir, Improved therapies have dramatically increased our ability to suppress RA disease activity. Short-term goal-directed therapy or treat-to-target, central to the management of hypertension and diabetes, may be the next step to increase effectiveness of RA therapy, although recent recommendations for treat-to-target strategies acknowledge the limited data from routine care (RC) [1]. Nevertheless, inducing remission is a logical short-term goal in RA [2, 3]. Patients receiving DMARDs and achieving low disease states have less joint damage progression [4, 5]. Patient preferences for therapy outcomes consistently identify their priorities as reduced pain and maintenance of function [6, 7]. Our RA Centre service routinely uses goal-directed therapy (GDT) strategy, short-term goal DAS-28 remission (DAS-28 < 2.6). After 2 years, we tested if this strategy improved patient function, comparing RA Centre outcomes with those of clinics in the same hospital not using this strategy. An RC group of consecutive patients recruited from clinics where treatment aimed to reduce signs and symptoms with no precise goal, was compared with a matched sample of RA Centre patients, the GDT group. The Guys Hospital Research Ethics Committee approved the study and patients gave informed consent. Patients with RA (ACR 1987 revised criteria) [8] over the age of 18 years were recruited for assessment, with no disease- or comorbidity-related exclusion criteria. Groups were matched within disease duration ± 2 years, age ± 5 years and sex. Rheumatologists treating the RC group were not aware of the patient DAS-28 score. HAQ-Disability Index (DI) was not used to guide treatment in either clinic. RC patients were assessed on a single occasion with joint counts and global disease activity performed by a research nurse not involved in therapy decisions. Fishers exact tests were used for categorical data, and Wilcoxon signed rank sum tests for paired continuous data, almost all non-normally distributed. Multiple logistic regression assessed clinical factor contributions to achieving remission, and multivariable linear regression assessed influences on HAQ. Analyses were performed using SPSS 15.0 and Graph Pad Prism 5. Ninety patients were recruited to the RC group and data compared with that collected contemporaneously from matched GDT patients. More GDT patients received combination DMARDs (12 vs 3%, P = 0.048) but not biologics (20 vs 13%, P = 0.32). Multiple regression analysis identified DAS-28, age, disease duration and pain VAS as independent predictors of HAQ-DI, with the highest contribution from DAS-28. Patients in the GDT group with disease duration up to 15 years showed significantly improved function compared with RC, with increasingly large differences in patients with shorter disease duration (Fig. 1A). Significantly more GDT patients achieved remission at all disease duration periods (Fig. 1B). Multiple logistic regression including all patients (disease duration up to 30 years) showed males were less likely to achieve remission [odds ratio (OR) 0.3; 95% CI 0.1, 0.8], and patients without erosions were more likely to achieve remission (OR 2.9; 95% CI 1.1, 8.2). In patients with disease duration up to 15 years, only GDT was influential in achieving remission (OR 5.7; 95% CI 1.5, 21.7). Fig. 1 Goal-directed therapy increases the numbers of patients in remission and reduces HAQ in patients up to disease duration of 15 years. (A) Median HAQ is significantly lower in the GDT group at a range of disease durations. (B) Remission was defined by DAS-28 < 2.6; ... This study of outcomes in routine hospital clinics using standard medication regimens shows that a DAS-28 goal-directed strategy is associated with significantly improved function for patients with disease duration up to 15 years. DAS-28 remission achievers had significantly better HAQ scores compared with non-achievers. DAS-28 remission rates were significantly better in the GDT group with RA >15 years, but HAQ scores were not better. This may reflect clinical trial results, where patients with longer disease duration have smaller HAQ improvements despite similar DAS-28 improvements [9]. Secondly, GDT patients with disease up to 5 years, receiving 2 years of GDT, achieved much higher remission rates (39%) compared with RC patients (9%). We assessed unselected patients attending routine outpatient clinics. As such, these results are relevant to general rheumatology clinic populations. In contrast to most studies of goal-directed therapy studying early arthritis, our patients had longer disease duration. We also demonstrate the challenges of achieving remission in unselected populations. Many patients declined increases in therapy or had co-morbidities preventing intensified therapy. Our patients were not selected by consenting to a treatment protocol, and therapy decisions were the usual consensus of rheumatologist advice, assessed from the patients perspective. The concept of patient acceptable symptom state (PASS) may explain this reluctance. A large study of RC patients, with a mean disease duration of 7.6 years, showed that the DAS-28 score cut-off for PASS status was 4.05 [10]. Additionally, in the UK, biologic therapy is only available for patients with DAS-28 > 5.1. In conclusion, a goal-directed or treat-to-target strategy can be successfully utilized in RC to achieve higher remission rates, and is associated with better function in patients with early and medium disease duration. HAQ-DI for patients in remission was significantly lower than those not in remission, suggesting that DAS-28 remission is a relevant goal to improve function.