Etanercept reduces synovitis as measured by magnetic resonance imaging in patients with active rheumatoid arthritis after only 6 weeks

OBJECTIVE: To demonstrate the efficacy of etanercept to reduce synovitis as measured by magnetic resonance imaging (MRI) as early as 6 weeks after starting treatment in patients with active rheumatoid arthritis (RA). METHODS: Twenty-two patients with active RA despite disease modifying antirheumatic drug (DMARD) treatment were included in this prospective, controlled study. Patients were randomized in 2 groups. In the treatment group, etanercept was added at usual doses during 6 weeks. In the control group, patients continued with prior DMARD therapy. MRI of the dominant wrist and 2nd-5th MCP joints were obtained at baseline and at 6 weeks and evaluated according to OMERACT recommendations. Results of changes in synovitis in the treatment group were compared with changes in the control group. RESULTS: Changes in synovitis measured by MRI of the hand (OMERACT evaluation) in the etanercept group showed a significant reduction after 6 weeks of treatment compared with no changes in the control group. Reduction of synovitis in the treatment group also showed good correlation with decrease of various clinical and laboratory measures. CONCLUSION: In patients with active RA despite DMARD therapy, etanercept, but not placebo, reduced synovitis as measured by MRI after 6 weeks.     

Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFalpha therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement

OBJECTIVE: To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. METHODS: 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. RESULTS: At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50). CONCLUSIONS: Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy.     

An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis

OBJECTIVE: Achieving remission is the aim of treatment in rheumatoid arthritis (RA). This should represent minimal arthritis activity and ensure optimal disease outcome. However, we have previously demonstrated a high prevalence of imaging-detected synovial inflammation in RA patients who were in clinical remission. The purpose of this study was to evaluate the long-term significance of subclinical synovitis and its relationship to structural outcome. METHODS: We studied 102 RA patients receiving conventional treatment who had been judged by their consultant rheumatologist to be in remission, as well as 17 normal control subjects. Subjects underwent clinical, laboratory, functional, and quality of life assessments over 12 months. In addition to standard radiography of the hands and feet, imaging of the hands and wrists was performed with musculoskeletal ultrasonography (US) and conventional 1.5 T magnetic resonance imaging (MRI) at baseline and 12 months, using validated acquisition and scoring techniques. RESULTS: Despite their being in clinical remission, 19% of the patients displayed deterioration in radiographic joint damage over the study period. Scores on musculoskeletal US synovial hypertrophy, power Doppler (PD), and MRI synovitis assessments in individual joints at baseline were significantly associated with progressive radiographic damage (P=0.032, P<0.001, and P=0.002, respectively). Furthermore, there was a significant association between the musculoskeletal US PD score at baseline and structural progression over 12 months in totally asymptomatic metacarpophalangeal joints (P=0.004) and 12 times higher odds of deterioration in joints with increased PD signal (odds ratio 12.21, P<0.001). CONCLUSION: Subclinical joint inflammation detected by imaging techniques explains the structural deterioration in RA patients in clinical remission who are receiving conventional therapy. Our findings reinforce the utility of imaging for the accurate evaluation of disease status and the prediction of structural outcome.     

Influence of disease-modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: results from a large observational inception study

OBJECTIVE: To determine the effect of early treatment with disease-modifying antirheumatic drugs (DMARDs) in reducing radiographic progression over a 5-year period in patients with new-onset inflammatory polyarthritis. METHODS: Three hundred thirty-five consecutive patients with paired radiographs obtained 1 year and 5 years after enrollment in a population-based arthritis register were studied. Logistic regression was used to model differences in baseline factors associated with the start of DMARDs. The time from symptom onset to first use of DMARDs was stratified to represent 4 groups: no DMARD use, <6 months, 6-12 months, and >12 months. Radiographs of the hands and feet were scored using the Larsen method. Progression in the Larsen score was evaluated as a 5-year score adjusted for the first film score. Negative binomial regression was used to compare Larsen score progression for each of the 3 treatment groups with that for patients not receiving DMARDs. Results were then adjusted for severity, based on propensity modeling. RESULTS: Patients who received treatment had more radiographic progression than did patients who were untreated. Coefficients (95% confidence intervals), expressed as a multiple of the Larsen score in DMARD-treated patients compared with untreated patients, were as follows: 1.6 (1.1-2.3) for <6 months, 2.4 (1.5-3.6) for 6-12 months, and 2.0 (1.4-2.8) for >12 months. As expected, patients receiving treatment had more severe disease at baseline. Using the propensity score as a method of adjusting for disease severity, the influence of treatment on outcome became attenuated as follows: 1.1 (0.8-1.7) for <6 months, 1.6 (1.0-2.6) for 6-12 months, and 1.5 (1.0-2.2) for >12 months. This effect was also seen in the crude Larsen score at year 5. CONCLUSION: In this observational study, DMARD treatment was a marker not only of worse disease at presentation but also of the radiographic state and radiographic progression at 5 years. After adjustments were made for baseline disease severity, earlier therapy was shown to have a beneficial effect on outcome.     

Response to intramuscular methyl prednisolone in inflammatory hand pain: evidence for a targeted clinical, ultrasonographic and therapeutic approach

BACKGROUND: Hand pain with stiffness is a common clinical presentation to early arthritis clinics, with outcome varying from resolution to the development of rheumatoid arthritis. OBJECTIVE: To assess the response and predictors of response to intramuscular methylprednisolone (MP) and hydroxychloroquine (HCQ) using a standardised treatment protocol. METHODS: Patients with inflammatory hand pain (IHP), defined as predominantly hand pain and morning stiffness of at least 30 min duration, received a standardised assessment prior to receiving intramuscular MP. Response (primary outcome) at 4 weeks was a 50% improvement in symptoms as perceived by the patient; responders who relapsed received repeat intramuscular MP and HCQ. RESULTS: 102 patients were recruited, of which 21% were rheumatoid factor (RF) positive, 23% had clinical synovitis, 25% had raised C-reactive protein level and 55% had ultrasound-detected synovitis. 73% responded, with associated significant reductions in morning stiffness, Health Assessment Questionnaire, painful and tender joint counts, and visual analogue scores (p < or = 0.006 for all). Ultrasound-detected synovitis (p<0.001) and RF (p = 0.04), but not clinical synovitis (p = 0.74), were significantly associated with response to intramuscular MP. 86% who remained on HCQ long term reported a benefit. CONCLUSIONS: Patients with IHP have significant improvement in symptoms and function following intramuscular MP. Further placebo-controlled trials are required to assess the role of intramuscular MP and ultrasonography in managing this patient group.     

Disease-modifying Antirheumatic Drug Use in the Treatment of Juvenile Idiopathic Arthritis: A Cross-sectional Analysis of the CARRA Registry

OBJECTIVE: To characterize disease-modifying antirheumatic drug (DMARD) use for children with juvenile idiopathic arthritis (JIA) in the United States and to determine patient factors associated with medication use. METHODS: We analyzed cross-sectional baseline enrollment data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from May 2010 through May 2011 for children with JIA. Current and prior medication use was included. We used parsimonious backward stepwise logistic regression models to calculate OR to estimate associations between clinical patient factors and medication use. RESULTS: We identified 2748 children with JIA with a median disease duration of 3.9 years from 51 US clinical sites. Overall, 2023 (74%) had ever received a nonbiologic DMARD and 1246 (45%) had ever received a biologic DMARD. Among children without systemic arthritis, methotrexate use was most strongly associated with uveitis (OR 5.2, 95% CI 3.6-7.6), anticitrullinated protein antibodies (OR 4.5, 95% CI 1.7-12), and extended oligoarthritis (OR 4.1, 95% CI 2.5-6.6). Among children without systemic arthritis, biologic DMARD use was most strongly associated with rheumatoid factor (RF)-positive polyarthritis (OR 4.3, 95% CI 2.9-6.6), psoriatic arthritis (PsA; OR 3.0, 95% CI 2.0-4.4), and uveitis (OR 2.8, 95% CI 2.1-3.7). Among children with systemic arthritis, 160 (65%) ever received a biologic DMARD; tumor necrosis factor inhibitor use was associated with polyarthritis (OR 2.5, 95% CI 3.8-16), while interleukin 1 inhibitor use was not. CONCLUSION: About three-quarters of all children with JIA in the CARRA Registry received nonbiologic DMARD. Nearly one-half received biologic DMARD, and their use was strongly associated with RF-positive polyarthritis, PsA, uveitis, and systemic arthritis.     

Current treatment paradigms in rheumatoid arthritis

Rheumatoid arthritis (RA) has traditionally been treated using the pyramid approach, in which non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment and disease-modifying anti-rheumatic drugs (DMARDs) are introduced relatively late in the disease. This approach is no longer valid. Previously regarded as a benign disease, RA is now recognized as causing substantial morbidity and mortality, as do the NSAIDs used in treatment. DMARDs are more effective in controlling the pain and disability of RA than NSAIDs, and are often no more toxic. The current treatment paradigm emphasizes early, consistent use of DMARDs. A 'sawtooth' strategy of DMARD use has been proposed, in which a rising but low level of disability triggers a change in therapy. Determining the most clinically useful DMARD combinations and the optimal sequence of DMARD use requires effectiveness studies, Bayesian approaches and analyses of long-term outcomes. Such approaches will allow optimization of multiple drug therapies in RA, and should substantially improve the long-term outcome for many patients.     

In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24?weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline

We aimed to evaluate the efficacy of tocilizumab in patients with rheumatoid arthritis (RA), using the clinical disease activity index (CDAI), and to determine the baseline variables associated with CDAI remission. Fifty-eight patients with active RA were enrolled. We tried to evaluate whether baseline variables were associated with CDAI remission at 24?weeks. Twenty-two of the 58 patients (37.9%) had received tumor necrosis factor (TNF) inhibitors. The continuation rate of tocilizumab at 24?weeks was 87.9%. The seropositivity rates of IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies at baseline were both 91.4%. The rate of CDAI remission at 24?weeks was 20.7%. We selected baseline variables including age, gender, duration of disease, concomitant use of glucocorticoids, concomitant use of methotrexate (MTX), previous anti-TNF therapy, titer of anti-CCP antibodies (high or low toward median), titer of IgM-RF (high or low toward median), and CDAI, and found that a high titer of IgM-RF was the only variable to be associated with CDAI remission, according to univariate and logistic regression analyses. This is a new finding, and may be specific to tocilizumab as compared with previous observations in anti-TNF therapy.     

A randomized controlled trial of early intervention with intraarticular corticosteroids followed by sulfasalazine versus conservative treatment in early oligoarthritis

OBJECTIVE: To determine the outcome after 52 weeks of early intervention with intraarticular corticosteroid injections followed by sulfasalazine versus conservative therapy in patients with recent-onset oligoarthritis in a randomized controlled trial. METHODS: Patients with 相似文献   

Influence of disease‐modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: Results from a large observational inception study

Objective

To determine the effect of early treatment with disease‐modifying antirheumatic drugs (DMARDs) in reducing radiographic progression over a 5‐year period in patients with new‐onset inflammatory polyarthritis.

Methods

Three hundred thirty‐five consecutive patients with paired radiographs obtained 1 year and 5 years after enrollment in a population‐based arthritis register were studied. Logistic regression was used to model differences in baseline factors associated with the start of DMARDs. The time from symptom onset to first use of DMARDs was stratified to represent 4 groups: no DMARD use, <6 months, 6–12 months, and >12 months. Radiographs of the hands and feet were scored using the Larsen method. Progression in the Larsen score was evaluated as a 5‐year score adjusted for the first film score. Negative binomial regression was used to compare Larsen score progression for each of the 3 treatment groups with that for patients not receiving DMARDs. Results were then adjusted for severity, based on propensity modeling.

Results

Patients who received treatment had more radiographic progression than did patients who were untreated. Coefficients (95% confidence intervals), expressed as a multiple of the Larsen score in DMARD‐treated patients compared with untreated patients, were as follows: 1.6 (1.1–2.3) for <6 months, 2.4 (1.5–3.6) for 6–12 months, and 2.0 (1.4–2.8) for >12 months. As expected, patients receiving treatment had more severe disease at baseline. Using the propensity score as a method of adjusting for disease severity, the influence of treatment on outcome became attenuated as follows: 1.1 (0.8–1.7) for <6 months, 1.6 (1.0–2.6) for 6–12 months, and 1.5 (1.0–2.2) for >12 months. This effect was also seen in the crude Larsen score at year 5.

Conclusion

In this observational study, DMARD treatment was a marker not only of worse disease at presentation but also of the radiographic state and radiographic progression at 5 years. After adjustments were made for baseline disease severity, earlier therapy was shown to have a beneficial effect on outcome.

     

Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting

OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.     

Daily practice effectiveness of a step-down treatment in comparison with a tight step-up for early rheumatoid arthritis

OBJECTIVE: To study prospectively the daily practice effectiveness of a step-down early rheumatoid arthritis (RA) treatment strategy. METHODS: Patients with severe RA and no contra-indications were proposed step-down therapy, the others step-up. Step-down patients received a modified combination therapy in early RA (COBRA) regimen: sulphasalazine (SPS), 2 g daily, and methotrexate (MTX), 15 mg weekly, combined with step-down oral prednisolone (start 60 mg daily, fast tapering to 7.5 mg over 6 weeks, discontinuation from week 28). At week 40, patients were randomized to maintenance therapy with either SPS or MTX if disease activity score-28 (DAS28) was acceptably low. The step-up group started disease-modifying anti-rheumatic drug (DMARD) monotherapy. In both groups, treatment was adjusted at follow-up, based on DAS28. DAS28, functionality Health Assessment Questionnaire (HAQ), adverse events, DMARD changes and steroid use were registered 4-monthly for 2 yrs. RESULTS: Nineteen patients received step-down and 52 step-up treatment. More patients completed the first year without unplanned DMARD changes and without dosage adjustment and fewer had DMARD changes due to side effects or inefficacy in the step-down group compared with step-up, whereas the number of adverse events was comparable. MTX proved to be the most effective maintenance therapy after step-down. The DAS response, proportion of patients in remission, HAQ response and proportion of patients without disability at 4 months was higher in the step-down group. CONCLUSIONS: In daily practice, a step-down treatment strategy for early RA is more effective than a step-up approach.     

Efficacy of certolizumab pegol with and without concomitant use of disease-modifying anti-rheumatic drugs over 4 years in psoriatic arthritis patients: results from the RAPID-PsA randomized controlled trial

To report long-term efficacy of certolizumab pegol (CZP) treatment with and without concomitant DMARDs in patients with psoriatic arthritis (PsA). RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 216. Patients had active PsA with ≥?1 failed DMARD. At baseline, patients were randomized 1:1:1 to CZP 200 mg every 2 weeks: CZP 400 mg every 4 weeks: placebo. CZP-randomized patients continued their dose into open-label. Observed case efficacy data are reported to week 216 for week 0 CZP-randomized patients (dose combined) with and without baseline DMARD use (DMARD+/DMARD?). Dactylitis (tenderness and ≥?10% difference in swelling between affected and opposite digits) and enthesitis were measured using Leeds Dactylitis Index (LDI) and Leeds Enthesitis Index (LEI). 273/409 randomized patients received CZP from baseline: 199/273 (72.9%) DMARD+ and 74/273 (27.1%) DMARD? patients. 141/199 (70.9%) DMARD+ and 42/74 (56.8%) DMARD? patients completed Week 216. DMARD+ (79.7%) and 83.3% of DMARD? patients achieved ACR20 response at week 216; 79.2 and 78.1% achieved 75% improvement from baseline in Psoriasis Area and Severity Index (PASI75). High proportions of DMARD+/DMARD? patients with extra-articular manifestations at baseline reported total resolution at week 216; dactylitis 91.4% of DMARD+ and 93.3% of DMARD? patients, enthesitis 74.4% of DMARD+ and 87.5% of DMARD? patients. Long-term improvements in PsA symptoms were observed with CZP monotherapy or concomitant DMARDs, across important psoriatic disease domains, including joint disease, psoriasis, nail disease, dactylitis, and enthesitis.Trial registration: NCT01087788     

Loss of functional capacity caused by a delayed onset of DMARD therapy in rheumatoid arthritis. Long-term follow-up results of the Keitel function test Brief definite report

Summary The aim of this analysis was to investigate the impact of the postponement of DMARD therapy on the functional outcome of rheumatoid arthritis after 10 years of disease. 321 individuals with a disease duration of at least ten years were selected out of a cohort of more than 1800 patients. Two groups were analysed separately: patients who started DMARD therapy within the first year of their disease, and patients who received their first DMARD not earlier than five years after the onset of RA. The Keitel functional index was determined in every patient after 10 years of RA. After 10 years of disease, the swollen joint count and the ESR had decreased in both groups to a comparable degree. However, patients with early treatment performed significantly better in the Keitel test compared to the group with delayed therapy. Although patients with seropositive RA or rheumatoid nodules had a worse outcome in general, the benefit of early treatment was also significant in these subgroups. Received: 27 December 1999 Accepted: 22 December 2000     

Therapeutic strategies in rheumatoid arthritis over a 40-year period

OBJECTIVE: To examine trends in therapeutic strategies and to identify the determinants of starting disease modifying antirheumatic drug (DMARD) therapy over a 40-year period in a population based inception cohort of patients with rheumatoid arthritis (RA). METHODS: A population based inception cohort was assembled from among all Rochester, Minnesota, residents aged > or = 18 years who were first diagnosed with RA (1987 American College of Rheumatology criteria) between January 1, 1955, and January 1, 1995. All subjects were followed longitudinally through their complete medical records until death, migration from Olmsted County, or date of abstraction (January 1, 2001, to January 1, 2003). Drug exposure data were collected on all DMARD and corticosteroid regimens. Time to DMARD initiation was examined using the Kaplan-Meier method. The influence of calendar time and disease characteristics on time from incidence to first DMARD therapy and the number of DMARD regimens were analyzed using Cox regression and proportional odds models, respectively. RESULTS: The study population comprised 603 patients (73% female) with a mean age of 58 years and a mean followup of 15 years. At 2 years after RA onset, 26% of patients in the 1955-74 cohort, 40% in the 1975-84 cohort, and 70% in the 1985-94 cohort had received a DMARD (log-rank p < 0.001). Age, rheumatoid factor (RF) positivity, erythrocyte sedimentation rate, large joint swelling, rheumatoid nodules, and destructive changes on radiographs were significantly associated with time to first DMARD regimen after adjustment for calendar time and sex. Patients who were older and RF positive and who did not receive CS were more likely to have received more DMARD regimens. CONCLUSION: Time to initiation of DMARD therapy has shortened markedly over the past 3-4 decades. These changes in management of early RA provide evidence for the translation of scientific evidence into clinical practice in rheumatology. Age and various disease characteristics are significantly associated with initiation and the number of DMARD regimens used. These should be considered as confounders when examining the effect of early DMARD treatment on disease progression and mortality.     

Treating rheumatoid arthritis early with disease modifying drugs reduces joint damage: a randomised double blind trial of sulphasalazine vs diclofenac sodium

BACKGROUND: Current disease management in rheumatoid arthritis (RA) has moved towards "inverting the therapeutic pyramid" by introducing disease-modifying anti-rheumatic drugs (DMARDs) early. Despite the logic of early DMARD therapy, there is a dearth of supportive evidence for this approach. We report a randomised controlled trial comparing sulphasalazine monotherapy with diclofenac monotherapy in early RA. The primary aim was to provide unequivocal evidence that early DMARDs prevent erosive damage. The secondary aim was to evaluate if sulphasalazine used alone has comparable symptomatic benefits to NSAIDs. METHODS: 117 patients with RA for under 12 months of diagnosis (mean 2 months) were randomised (62 sulphasalazine; 55 diclofenac). Sulphasalazine patients comprised 76% women, and 58% were rheumatoidfactor positive. Diclofenac patients comprised 74% women, and 54% were seropositive. 36% completed 12 months of therapy (16 sulphasalazine; 26 diclofenac); sulphasalazine was given for a mean period of 21 weeks and diclofenac for a mean period of 33 weeks. Results were analysed on an intention to treat basis. RESULTS: After 12 months the mean number of new erosions in patients randomised to receive sulphasalazine was 2.0 (95%CI 0.9, 3.1) and in patients randomised to receive diclofenac was 7.5 (95%CI 4.1, 10.9; p = 0.002 by Student's unpaired t-test). An analysis of valid compliant completers showed the mean number of new erosions in patients who received 12 months therapy with sulphasalazine was 2.3 (95%CI 0.6, 4.0) and in patients who received 12 months diclofenac was 10.5 (95%CI 5.0, 15.9; p = 0.018 by Student's unpaired t-test). The Ritchie articular index, swollen joint counts and pain scores decreased with both sulphasalazine and diclofenac, with mean falls in both groups of 15-20% at 2 weeks and 30-40% at 4 and 8 weeks. There were no differences between treatments. Disease activity scores showed similar highly significant mean decreases within both treatment groups (P < 0.001 in all cases) of 0.5 at 2 weeks and 1.0 at 4 weeks; at 12 and 26 weeks they were significantly lower with sulphasalazine (p = 0.036 and 0.045). 75% of the patients given sulphasalazine and 65% of those given diclofenac had one or more adverse events with no major differences between treatments. CONCLUSIONS: These results show that an accelerated dosing schedule of sulphasalazine has identical effects to diclofenac in reducing symptoms, indicating it is a rapidly effective DMARD. They also provide unequivocal evidence, analysed on an intention to treat basis, that early treatment with sulphasalazine significantly reduces the extent of radiological progression in active RA.     

How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to 'non-aggressive' DMARD treatment and perspective from a 2-yr open label trial

OBJECTIVE: To determine what baseline factors might be associated with response to an initial mild treatment regimen in patients with early rheumatoid arthritis (RA). METHODS: Open label 2-yr study of 111 consecutive patients with early RA of duration less than 1 yr. None of the patients had previously received disease-modifying anti-rheumatic drugs (DMARDs). All patients were assigned to receive hydroxychloroquine (HCQ) at enrollment, and could also take non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. At any point during follow-up, patients not fulfilling the American College of Rheumatology (ACR) 50 criteria for improvement and/or who were taking prednisone > 10 mg/day were considered treatment failures and therapy changed to methotrexate (MTX), 7.5-20 mg/week. Clinical, laboratory and immunogenetic factors potentially predictive of treatment assignment at month 24 were evaluated. RESULTS: After 24 months of follow-up, a majority of patients (56/94) were either still on solo DMARD therapy with HCQ (n = 49) or off DMARD therapy with controlled/quiescent disease (n = 4), and 38 patients were taking MTX (including 11 in combination with other DMARDs). At month 24, all but 9 patients met ACR50 criteria for treatment response. Features present at enrollment which were predictors of MTX therapy at month 24 were high pain score, baseline rheumatoid factor titre > 1:40, higher number of swollen joints, and poor patient global assessment. The presence of HLA-C7xx at enrollment was also predictive of need for MTX therapy. CONCLUSIONS: This study suggests that even milder treatment with HCQ is greatly beneficial in patients with early RA. There continue to be very few consistently reliable predictors of treatment needs in patients with this disease.     

Toward a definition and method of assessment of treatment failure and treatment effectiveness: the case of leflunomide versus methotrexate

OBJECTIVE: Time to treatment discontinuation (TTD) is an accepted method of assessing treatment effectiveness in the community, but is susceptible to channeling bias and secular and cohort effects. In addition, TTD does not consider the addition of new disease modifying antirheumatic drugs (DMARD) to insufficiently effective therapies. We expand the definition of treatment failure to include discontinuation or addition of a second DMARD (1) to examine leflunomide (LEF) versus methotrexate (MTX) effectiveness in clinical practice; (2) to obtain an estimate of overall clinical effectiveness; and (3) to identify factors associated with treatment successes and failure. In addition, (4) we test the feasibility of performing a clinical trial using a longitudinal data bank. METHODS: Using the National Data Bank for Rheumatic Diseases longitudinal data bank, 1431 patients with rheumatoid arthritis (RA) who began taking LEF or MTX as part of their routine medical care were followed from 1998 through 2001. None of the 1431 patients had received either treatment previously. Patients were assessed at 6 month intervals for periods up to 36 months by mailed questionnaires concerning DMARD therapy and demographic and RA severity factors. Kaplan-Meier survivor functions and Cox regression analyses were used to assess treatment failure, defined as time to discontinuation or to the addition of a second DMARD. RESULTS: For 756 patients taking LEF, the failure rate was 55.5 per 100 patient-years, and the median time to failure was 15 (95% CI 13, 17) months. For 675 patients taking MTX the failure rate was 57.3 per 100 patient-years, and the median failure time was 14 (95% CI 12, 18) months. These differences were not statistically significant. The overall rate of discontinuation was 68.7% of the failure rate. Discontinuation was predicted by adverse effects [hazard ratio 1.76 (95% CI 1.51, 2.04)] and by clinical status prior to starting DMARD, and these results were not affected by specific DMARD treatment. Discontinuation was more common with LEF, and addition of a second DMARD was more common with MTX. More than 77% of treatment failures, defined by use of additional therapy, resulted in starting anti-tumor necrosis factor treatment rather than a conventional DMARD. CONCLUSION: In an observational clinical trial using a contemporary longitudinal data bank, with time to treatment failure as the outcome, LEF and MTX had equal effectiveness as measured by time to treatment failure. Treatment failure rates were substantially greater than noted historically. Given the availability of many efficacious additional treatment options, this increase in failure rate appears to reflect a greater propensity to discontinue and/or add therapy.     

Subclinical synovitis measured by ultrasound in rheumatoid arthritis patients with clinical remission induced by synthetic and biological modifying disease drugs

BackgroundRheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage.ObjectiveTo determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF.MethodsHospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0 = none to 3 = severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N = 37) and combination therapy with DMARD and anti-TNF (N = 21) groups. A p-value <0.05 was considered statistically significant.ResultsOut of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found.ConclusionsPersistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission.