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 Guy's 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. Fisher's 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;
increased numbers of patients were in remission at all disease durations in the GDT
group. *P < 0.05, **P < 0.01.
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 patient's 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.