Cost effectiveness analysis of disease modifying antirheumatic drugs in rheumatoid arthritis

The objective was to assess the cost-effectiveness of various DMARDs compared with antimalarials (AM) for rheumatoid arthritis (RA) treatment. The data on disease activity, functional status and societal costs were collected from a 1-year cohort of 152 patients with RA receiving at least one DMARD for ≥ 6 months. Incremental cost effectiveness ratio (ICER) was calculated from the societal costs of DMARD treatment compared with AM per one unit of HAQ improvement. All costs were presented in 2001 US dollars. Mean (SD) societal cost of AM treatment was US$ 2,285 (1,154) per patient per year. MTX + AM was less costly and more effective than AM, as the ICER of this combination would save US$ 834 per 1 U of HAQ improvement. MTX + SSZ, leflunomide, and triple therapy (AM + MTX + SSZ) were more effective than AM with additional costs. RA treatment with non MTX-based DMARDs was not cost-effective.     

The methotrexate therapeutic response in rheumatoid arthritis

OBJECTIVE: Methotrexate (MTX) is used frequently as a disease modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), and patients tend to continue taking this drug for longer periods than alternative single agents. The shape of the therapeutic response beyond one or 2 years, however, has not been fully studied. We examined the properties of the pure MTX "therapeutic segment," that period that begins with start of MTX and terminates when MTX is discontinued or another DMARD is added, by observational study. METHODS: We studied new MTX starts for the period 1988 through 1996 for 437 patients from a parent cohort of 4253 patients. Patients were drawn from 8 Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) data centers: 2 community based populations; 2 private rheumatological practices; 2 university referral practices; and 2 university clinics for underserved minority urban populations. Health Assessment Questionnaire (HAQ) Disability Index scores (0-3) were obtained prospectively each 6 months. RESULTS: At MTX start, patients had relatively long average disease duration of 16.7 years, and had moderately severe disability, with an initial HAQ mean disability score of 1.48. Over the 10 year period examined in the parent cohort of 4253 patients (and thus irrespective of therapy), the prevalence of MTX use rose from 19% to 45%, while mean HAQ disability declined from 1.34 to 1.11. This correspondence is consistent with an accrual of benefits from more frequent use of MTX and other DMARD over this period. The MTX therapeutic segment revealed a distinct shape. HAQ-Disability Index values began at 1.48 at baseline and declined to a maximal improvement of 1.23 at 30 months. This long period to maximum benefit may have been partly driven by a slow titration upward to an optimal dosage. After 42 months, disability for this population began to re-progress and reached 1.39 at 84 months, still below the pretreatment baseline. Re-progression to baseline was about 8 or more years. Cumulative disability averted with MTX treatment for this population was roughly 1.30 disability-unit-years. CONCLUSION: MTX treatment of RA in practice differs substantially from common perception and appears suboptimal by being too little, too late, and too long to treatment change. A modification of the "sawtooth strategy" in which the disease is "ratcheted down" by change of MTX therapy at 3 years or when re-progression has proceeded halfway to baseline, rather than waiting for return to baseline, is suggested by these data. Also suggested is the need for more rapid upward dosage titration and longer maintenance of an optimal or highest tolerated dosage. "Therapeutic segment" data provide insights into strategic approaches to management of RA since they allow estimation of population aggregate properties such as time to maximum benefit and the time to return to baseline.     

Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis

OBJECTIVE: Based on comparisons of short-term cohort studies or cross-sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years. METHODS: We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985-1990, 1990-1995, 1995-2000, 2000-2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts. RESULTS: The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease-modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy. CONCLUSION: The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.     

The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses

BACKGROUND: Therapy of rheumatoid arthritis (RA) is typically characterized by the sequential use of disease-modifying anti-rheumatic drugs (DMARDs). This study aimed to reveal treatment patterns with traditional DMARDs and their changes during the two decades before the recent introduction of new DMARDs. METHODS: A total of 593 RA patients were followed from their first presentation to our clinic throughout the course of their disease; 222 patients received their first DMARD therapy while under our care. More than 2,300 patient years of therapy were analysed for the efficacy [using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as surrogates] and duration of drug therapy of consecutive DMARDs. RESULTS: Before 1985, 65-90% of initial DMARDs were gold compounds, but their use decreased continuously thereafter. Antimalarial (AM) drugs were important initial DMARDs in new patients at all times, whereas sulphasalazine (SSZ) and methotrexate (MTX) gained increasing significance after 1985 (the first DMARD was MTX in up to 29% of new patients). Penicillamine (DPA), azathioprine (AZP), cyclosporin (CyA) and combination therapies were not usually employed initially, but were reserved for the later course of the disease. Gender, age and rheumatoid factor were not different between patients receiving different DMARDs. The baseline acute-phase response was higher in patients treated with MTX (mean CRP 3.5 mg/dl) than in those treated with SSZ (CRP 2.4 mg/dl; P < 0.05) or AM (CRP 2.1 mg/dl; P < 0.05), suggesting that MTX was used preferentially in patients with high disease activity. On the other hand, once AM or SSZ had been discontinued, MTX was the most common subsequent DMARD (in 31 and 56% respectively). Comparison of first DMARDs with subsequent ones revealed that first DMARDs were more effective: the acute-phase response decreased most prominently during first therapies (CRP reduction was 1.28 mg/dl during first courses and 0.35 mg/dl during fourth or later courses; P < 0.01); and retention rates were significantly longer for first compared with subsequent therapies (median of 24.5 months for first and 18.6 months for fourth or subsequent therapies; P < 0.001). CONCLUSION: MTX was the most commonly employed DMARD therapy for RA and was used increasingly as first therapy in newly diagnosed RA. Patients with high disease activity were given MTX therapy more often than other DMARDs, while those with low activity were more likely to receive SSZ or AM, and MTX on failure of these drugs. First DMARDs in new patients were retained longer than subsequent DMARDs, apparently because they are more effective.     

Comparison of employability outcomes among patients with early or long-standing rheumatoid arthritis

OBJECTIVE: To compare employability between patients with early and long-standing rheumatoid arthritis (RA) and examine the relationships between improvement in employability and disease stage after adjustment for demographic characteristics, disease activity, physical functioning, and response to therapy. METHODS: We evaluated the employability data from 2 double-blind, randomized, placebo-controlled studies of infliximab plus methotrexate (MTX) in patients with RA. Patients were incomplete responders to MTX in 1 study and had never taken MTX in the other study. Patients age <65 years were categorized as having early RA (< or =3 years disease duration) or long-standing RA (>3 years disease duration). Physical functioning was assessed using the Health Assessment Questionnaire (HAQ) and clinical response was determined based on the American College of Rheumatology 20% improvement criteria (ACR20). RESULTS: Patients with early RA were more likely to be employable at baseline than those with long-standing RA, even after adjusting for baseline HAQ scores. Among patients who were not employable at baseline but achieved an ACR20 response after 1 year of treatment, after adjusting for baseline HAQ score, the patients with early RA who had never taken MTX were 3 times more likely to become employable compared with those with long-standing RA who had an incomplete response to MTX at baseline. CONCLUSION: In 2 clinical trials, patients with early RA were more likely to show improved employment outcomes after treatment than those with long-standing RA, suggesting intervention as early as possible in the disease course maximizes an individual patient's employment potential.     

Clinical and radiological disease-course in a Swedish DMARD-treated early RA-inception cohort: an observational study

OBJECTIVES: Disease-modifying anti-rheumatic drugs (DMARDs) decrease clinical signs and symptoms in rheumatoid arthritis (RA). However, radiographic changes sometimes continue to accrue despite effective suppression of clinical symptoms by therapy. The objective of this study was to identify whether successful clinical disease-control in a Swedish early RA-inception cohort of patients led to an attenuation of radiological progression. PATIENTS AND METHODS: We analysed clinical data and radiographs of 95 patients who were on a stable treatment regimen [methotrexate (MTX), sulfasalazine (SSZ), oral gold (AUR)] or who had changed between different DMARDs during the 2-year observation period [multiple therapy failures (mTF)]. Radiographs were quantified using the modified Larsen score and 'X-Ray RheumaCoach' software. RESULTS: Clinical measures improved markedly (p <0.001) from baseline to year 2 under AUR, MTX, and SSZ therapy but not in the mTF group. Similar levels of disease control were seen for each DMARD. During this period, patients treated with AUR had a deltaLarsen score (+ 14.5+/-1.3) similar to mTF patients (+ 15.8+/-1.1) but greater than patients on MTX (+8.6+/-0.8) or SSZ (+9.1+/-0.8). CONCLUSIONS: This study confirms that radiological progression occurs despite a clinically acceptable disease control, but also shows that, given the same degree of clinical disease control, radiological progression can be different for different DMARDs.     

Vertebral bone mineral density changes in female rheumatoid arthritis patients treated with low-dose methotrexate

OBJECTIVE: To assess vertebral bone mineral density (BMD) changes in rheumatoid arthritis (RA) patients taking low-dose methotrexate (MTX). METHODS: We evaluated in a 2-year, longitudinal study female RA patients, who had recently started a disease-modifying antirheumatic drug (DMARD), divided into two groups: group A, receiving MTX, and group B, receiving other DMARDs. Lumbar spine BMD was assessed at baseline and every year; RA activity was assessed every 3 months. RESULTS: Sixty-two patients were enrolled in the study; 40 completed the follow-up period: 22 of group A, and 18 of group B. The results after 2 years showed that both groups lost bone significantly vs baseline (p < 0.001) in a comparable fashion: group A (mean +/- SD) -3.9 +/- 4.9% vs group B -3.0 +/- 3.7% (p = NS). The patients who showed active disease lost significantly (p < 0.05) more bone (-5.5 +/- 3.8%) than those with less active disease (-1.1 +/- 3.6%), independently of their DMARD. CONCLUSION: Low-dose MTX in RA does not seem to exert relevant effects on trabecular bone.     

Optimal use of non-biologic therapy in the treatment of rheumatoid arthritis

With the evolution of therapies for RA, new treatment strategies and goals of therapy have evolved. Recent European League Against Rheumatism (EULAR) guidelines on the treatment of RA proposed three phases of therapy: phase I comprising first-line synthetic DMARD with or without glucocorticoid; phase II comprising second-line synthetic DMARD with or without glucocorticoid, or combination synthetic DMARD therapy, or (if prognostic factors are poor) first-line biologic DMARD; and phase III comprising alternative biologic DMARDs. In all phases, the key principle is tight control: striving to achieve a predefined goal of remission or low disease activity (treat to target) with frequent dose and medication adjustments tailored to the individual patient, preferably within the window of opportunity during early RA. In all phases, MTX is recognized as an anchor drug; it is characterized by proven efficacy in combination DMARD strategies, relatively low cost, relatively rapid onset of action, proven beneficial impact on radiological progression and mortality and a wide dose range that facilitates dose adjustments. Prednisone and its active metabolite, prednisolone, have similar characteristics, making them ideal anchor drugs too. The EULAR guidelines reserve a place for MTX and glucocorticoids in all phases of treatment. The second CAMERA (Computer Assisted Management in Early Rheumatoid Arthritis) study in early RA has demonstrated that including prednisone from the start in an MTX-based tight control strategy aimed at remission improves disease activity variables, time to remission, functional disability and radiological joint damage compared with the same strategy without prednisone. In conclusion, both MTX and prednisone play key roles in modern RA treatment strategies.     

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.     

Comparison of employability outcomes among patients with early or long‐standing rheumatoid arthritis

Objective

To compare employability between patients with early and long‐standing rheumatoid arthritis (RA) and examine the relationships between improvement in employability and disease stage after adjustment for demographic characteristics, disease activity, physical functioning, and response to therapy.

Methods

We evaluated the employability data from 2 double‐blind, randomized, placebo‐controlled studies of infliximab plus methotrexate (MTX) in patients with RA. Patients were incomplete responders to MTX in 1 study and had never taken MTX in the other study. Patients age <65 years were categorized as having early RA (≤3 years disease duration) or long‐standing RA (>3 years disease duration). Physical functioning was assessed using the Health Assessment Questionnaire (HAQ) and clinical response was determined based on the American College of Rheumatology 20% improvement criteria (ACR20).

Results

Patients with early RA were more likely to be employable at baseline than those with long‐standing RA, even after adjusting for baseline HAQ scores. Among patients who were not employable at baseline but achieved an ACR20 response after 1 year of treatment, after adjusting for baseline HAQ score, the patients with early RA who had never taken MTX were 3 times more likely to become employable compared with those with long‐standing RA who had an incomplete response to MTX at baseline.

Conclusion

In 2 clinical trials, patients with early RA were more likely to show improved employment outcomes after treatment than those with long‐standing RA, suggesting intervention as early as possible in the disease course maximizes an individual patient's employment potential.     

Is the disease course of rheumatoid arthritis becoming milder?: Time trends since 1985 in an inception cohort of early rheumatoid arthritis

Objective

Based on comparisons of short‐term cohort studies or cross‐sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years.

Methods

We used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985–1990, 1990–1995, 1995–2000, 2000–2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts.

Results

The DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease‐modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy.

Conclusion

The course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.

     

Contemporary disease modifying antirheumatic drugs (DMARD) in patients with recent onset rheumatoid arthritis in a US private practice: methotrexate as the anchor drug in 90% and new DMARD in 30% of patients

OBJECTIVE: To describe therapies with disease modifying antirheumatic drugs (DMARD) and biological agents in patients with early rheumatoid arthritis (RA) who were receiving routine clinical care in 2001 in a private practice of 5 rheumatologists in Nashville, TN, USA. METHODS: A cohort of 232 patients with initial symptoms of RA in 1998 or later were enrolled between February and October 2001 into a longterm observational study, designed to evaluate treatments and longterm outcomes of RA. The baseline evaluation included review of all DMARD that had been taken since disease onset, clinical measures on a multidimensional health assessment questionnaire, joint counts, and laboratory measures. RESULTS: Among the 232 patients, methotrexate (MTX) was the first DMARD used in 192 patients (82.8%), including 3 in combinations. Since initiation of the first DMARD to the study visit, over a median interval of 12.1 months, 125 (66.1%) patients of the 189 whose initial DMARD was MTX as a single DMARD continued MTX as a single DMARD, 43 (22.8%) had another DMARD or biological agent added in combination with MTX, and 21 (11.1%) discontinued MTX. Since the onset of RA, 89.2% of the patients had taken MTX, 15.9% hydroxychloroquine, 3.9% sulfasalazine, 22.0% leflunomide, 9.5% etanercept, 4.3 infliximab, and 87.0% prednisone. CONCLUSION: After a median duration of 12.1 months of DMARD therapy, almost 90% of patients with recent onset RA took MTX as the anchor drug. More than 60% took MTX as a single DMARD or in combination with traditional DMARD, while 30% took leflunomide, etanercept, or infliximab, usually in combination with MTX.     

Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis

OBJECTIVE: The response to single disease modifying antirheumatic drug (DMARD) is often suboptimal in patients with rheumatoid arthritis (RA). Thus, despite the limited data on the therapeutic efficacy of combination therapies, many patients are currently treated with a combination of DMARDs. METHODS: We studied prospectively the efficacy of combination therapy with DMARDs. The study was designed as a randomized trial and a single DMARD or two or three DMARD combinations were administered to 180 consecutive, age- and sex-matched patients with active RA, each of whom was followed up for a period of 2 years under treatment. Patients were divided into 3 groups which did not differ with regard to demographic, clinical and laboratory parameters. Patients in group I were treated with a single DMARD [methotrexate (MTX) 7.5-15 mg/week or sulfasalazine (SSZ) 1-2 g/day or hydroxychloroquine (HCQ) 200 mg/day], group II with MTX + SSZ or MTX + HCQ, and group III with a combination of all three drugs. Patients were re-evaluated at regular intervals by means of clinical and biochemical tests designed to detect specific rheumatic activity. Radiological assessments were also performed and scored according to Larsen by the same radiologist who was blinded to the treatment groups. RESULTS: At the end of the trial there were significant improvements in the clinical and laboratory parameters in all 3 groups. However, improvements were greater and much more significant in the patients who were given combination therapies. The combination of MTX + SSZ + HCQ was more effective than both monotherapy and the two-drug combinations. CONCLUSION: In conclusion, we suggest that patients with RA should be treated with combinations of DMARDs.     

The use of conventional disease-modifying anti-rheumatic drugs in established RA

Conventional disease-modifying anti-rheumatic drugs (DMARDs) are the main tool to treat any form of rheumatoid arthritis (RA). Over the years, treatment strategies and use of DMARDs have changed. 'Tight control' and 'treat-to-target' are now the present paradigms. Combining DMARDs and adapting their dosages to obtain the best (clinical) result in individual RA patients with the least amount of medication has been and is studied worldwide. Literature results are mainly on early RA however, and they do not necessarily also apply to patients with established RA. Methotrexate (MTX) is the key conventional DMARD also for the treatment of established RA, and MTX often has to be combined with other DMARDs to reach low disease activity. However, there is lack of data on combination DMARD strategies and on how to treat best individual patients with established RA. In this review, we address these uncertainties and give an overview of available data.     

Single-center, retrospective analysis of efficacy and safety of tacrolimus as a second-line DMARD in combination therapy and the risk factors contributing to adverse events in 115 patients with rheumatoid arthritis

To retrospectively evaluate the efficacy and safety of combination therapy with tacrolimus (TAC) and other disease-modifying antirheumatic drugs (DMARDs). One hundred fifteen rheumatoid arthritis (RA) patients treated with tacrolimus were enrolled in this retrospective analysis. We collected clinical information, including patient background, treatment efficacy (evaluated using the DAS score), and adverse events observed. Multiple logistic regression analysis was conducted to analyze factors contributing to clinical response and adverse effects. The disease activity score of 28 joints (DAS28) improved significantly at 24?weeks, and continuation rate at 1?year was 57.9%. There was no difference in continuation rate between different DMARD combinations, and not only methotrexate (MTX) but also bucillamine (BUC) and salazosulfapyridine (SSZ) were effective combination partners with TAC. No serious adverse events were observed, and no different inefficacy or safety was observed between non-elderly (<65?years old) and elderly (≥65?years old) RA patients. By conducting multiple logistic regression analysis, combination therapy with MTX and TAC, the number of baseline DMARDs (specifically, ≥3), and old age were identified as risk factors for adverse events. Our findings indicate that TAC is a valuable DMARD for second-line combination therapy in RA.     

What factors influence functional ability in patients with rheumatoid arthritis. Do they alter over time?

OBJECTIVES: To describe the changes in functional ability (FA) taking place over 5 yr in patients with rheumatoid arthritis (RA) starting disease-modifying anti-rheumatic drug (DMARD) therapy, to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment. METHODS: Three hundred and sixty-six patients with active RA were studied as part of a 5-yr randomized controlled study of DMARD therapy. FA was assessed by Health Assessment Questionnaire (HAQ) score every 6 months. Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr. The independent variables used were age, sex, visual analogue scale (VAS) pain, Ritchie articular index, C-reactive protein (CRP), Larsen score and log-transformed morning stiffness (EMS). RESULTS: Mean HAQ score was 1.64 at baseline, improved by 21% at 1 yr and gradually returned towards baseline levels by 5 yr. At baseline only 34% of variance in HAQ score could be explained; the most significant explanatory variables were the Ritchie articular index and CRP. At 5 yr the variance explained was 60%. The Ritchie articular index remained the strongest factor followed by VAS pain, log(10) EMS and Larsen score. CONCLUSIONS: Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr. The most consistent factor affecting function was joint tenderness. Global pain and duration of EMS were of lesser importance. Disease activity measures such as the CRP exerted an influence in the earlier, more active stages of disease: radiographic damage assumed greater importance as the arthritis progressed.     

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.