Combination Of DMARDs Research Articles

Comparison between DAS28, CDAI and HAQ-DI as tools to monitor early rheumatoid arthritis patients in eastern India

ABSTRACT Objective To investigate the relationship among DAS28, CDAI and HAQ-DI in early rheumatoid arthritis (RA) patients. Methods It was a prospective study on 61 consecutive DMARD naive early RA patients attending the outpatient department of a tertiary care hospital in eastern India. DAS28, CDAI and HAQ-DI were calculated at the initial visit. They were put on DMARD therapy as per protocol with categorization of disease activity as per the CDAI values. DAS28, CDAI and HAQ-DI were again calculated after 3 months. Statistical analysis was carried out. Results There was a significant correlation among HAQ-DI, DAS28 and CDAI values. HAQ-DI showed significant correlation with the individual variables used in CDAI and DAS28. These observations were noted both in the initial and after 3-month follow-up values. There was significant agreement between the disease activity categories obtained by CDAI and DAS28 cut-off levels. Combination DMARD therapy based on ACR 2008 recommendations resulted in significant improvement in disease activity and functional disability. Conclusion We can assess the disease activity in the patients by recording the HAQ-DI, at least in cases of early RA. Both DAS28 and CDAI are equally useful in assessing the disease activity of RA. These facts become important as it suggests that laboratory values do not remain absolutely essential in the assessment of the patients. These findings are especially important in a fund-stricken health system in developing countries like India.

Nonbiologic DMARD combination therapies cost effective in early RA

Nonbiologic DMARD combination therapies cost effective in early RA

Optimal care for early RA patients: the challenge of translating scientific data into clinical practice

Although the evidence is clear and most rheumatologists agree that RA should be treated early and intensively, it obviously remains a challenge to put this paradigm into practice. Patient- as well as physician-related factors determine the delay before the disease is recognized and treated appropriately. There is still a need for education in this context. Optimal treatment allocation depends on the determination of prognostic factors, but should also take into account the patient's perspective to be effective. Patients' perceptions about the disease and its medical management need to be adjusted as soon as possible. Initiation of intensive or complex treatment regimens is most feasible in a clinical setting, where rheumatologists work together with other health-care professionals, such as nurse specialists. Until now there does not seem to have been a difference in terms of efficacy between intensive RA treatment strategies based on a combination of classical DMARDs with glucocorticoids or with TNF-blocking agents, but given the costs biologicals cannot be considered first-line therapy. More scientific work is needed to identify individuals that could benefit from biologicals early in the disease. Given the long-term benefits of rapid disease control, health authorities should consider investing in a better implementation of intensive treatment regimens based on combinations of classical DMARDs and glucocorticoids.

Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity--the early RA network (ERAN)

To report from early RA network (ERAN) on Years 2 and 3 28-joint DAS (DAS-28) and HAQ outcomes in newly diagnosed RA patients treated with DMARD therapies stratified to DAS-28 status after 1 year. ERAN is a prospective observational cohort of newly diagnosed RA patients, monitored and treated according to local practice. Standardized case report forms are completed at first presentation, 3-6 months, 1 year and annually thereafter. A total of 418 newly diagnosed RA patients with 2 years and 302 with 3 years follow-up were identified in 22 ERAN centres from 2002 to 2008. Within their first year from registration, 67% of patients received monotherapy DMARDs, and 26% combination DMARDs including 2% were on anti-TNF therapies. Between Years 1 and 3, 60% received DMARD monotherapy, 34% combination DMARD therapy including 8% on anti-TNF therapies. Seventy-four per cent of patients with Year 1 DAS-28 < 3.2 and 27% with DAS-28 3.2-5.1 achieved a DAS-28 < 3.2 outcome at Year 2 [odds ratio (OR) 7.64; 95% CI 4.6, 12.6], and 71 and 35%, respectively, at Year 3 (OR 4.49; 95% CI 2.5, 7.9). Seventy-nine per cent of patients with a Year 1 DAS-28 < 3.2 and 52% with DAS-28 3.2-5.1 achieved an HAQ < 1.25 at Year 2 (OR 3.47; 95% CI 2.1, 5.6), and 81 and 47%, respectively, at Year 3 (OR 4.92; 95% CI 2.6, 9.0). In RA patients with a DAS-28 3.2-5.1 at 1 year, the likelihood of achieving a target low DAS-28 < 3.2, or a low HAQ, at Years 2 or 3 is poor in a routine care setting using conventional DMARDs according to current practice.

Tight control in early RA pays off in the long run

Clinical trials demonstrate that intensive treatment of early rheumatoid arthritis with a combination of DMARDs improves short-term outcomes. an extension study from a pivotal trial has now shown that such intensive early therapy can achieve a reduction in the rate of erosive progression over a period of 11 years.

Fish oil supplementation increases the cyclooxygenase inhibitory activity of paracetamol in rheumatoid arthritis patients

To examine interactions between fish oil and paracetamol for inhibition of prostaglandin synthesis in patients with rheumatoid arthritis (RA). Patients from an early RA clinic who were treated with a standardized combination DMARD regimen were enrolled. They were advised to consume an anti-inflammatory dose of fish oil containing the n-3 fatty acid, eicosapentaenoic acid (EPA), or a comparator oil. High EPA and Low EPA groups were defined by blood EPA levels >3.5% or <2%, respectively, of plasma phospholipid fatty acids. Participants provided a blood sample before, and 1h after ingestion of 1g paracetamol. The blood was incubated in different ways to allow measurement of COX-2 generated prostaglandin E(2) (PGE(2)) and COX-1 generated thromboxane A(2) (TXA(2)). Paracetamol suppressed the eicosanoid measures of COX-1 and COX-2 activities and the suppression was greater in the High EPA group. The results indicate that the combination of fish oil and paracetamol suppresses PGE(2) synthesis by an amount equivalent to that from maximum therapeutic doses of NSAIDs. Paracetamol is recommended for first-line use ahead of NSAIDs for symptom relief in RA or OA. Combining paracetamol with fish oil will enhance suppression of nociceptive PGE(2) synthesis and thereby may provide additive symptomatic benefits.

Pattern of Young and Old Onset Rheumatoid Arthritis (YORA and EORA) among a Group of Egyptian Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) differs depending on the age of disease onset. The differences between EORA and YORA are important because they have clinical and therapeutic implications. 1185 patients were ranked after classification according to age at onset of the disease into YORA I (16-40 years), YORA II (41-60 years) and EORA >60 years. All patients groups were compared, based on disease duration, disease activity, severity parameters and drug history. YORA I included 298 patients, 28.85% were males, with mean age of 29.4 ± 6 years and disease duration 4 ± 3.3 y, YORA II included 539 patients, 33.77% males, age 49.7 ± 6.1 y and disease duration 6.5 ± 5.6 y. EORA included 348 RA patients 40.5% males, age 67.1 ± 6.6 y, disease duration 9.95 ± 7.2 y. Activity was increased in EORA compared to YORA I and YORA II, while severity decreased in EORA. ESR, CRP and degree of anemia were higher in EORA. RF titer was higher in YORA. Small joints of the hands and feet were more involved in YORA, while, large joints in EORA. Rheumatoid nodules were increased in YORA I than EORA P = 0.04. Polymyalgia rheumatica was exclusively present in EORA group 25 patients 7.2%. Methotrexate was used in both YORA and EORA, with a higher mean of dosage in YORA than EORA. Multiple DMARDs in EORA was 57.9%, and biologics in 0.8% was which was significantly lower compared with YORA I, 86.3% and 1.7%, with P = 0.001. EORA has more active and less disabling and affects more males than YORA. The use of biologic therapy and combination DMARD therapy was less in EORA.

Rituximab and concomitant leflunomide for the treatment of rheumatoid arthritis

Rituximab has only been approved in combination with methotrexate for the treatment of rheumatoid arthritis. As some patients have intolerance to methotrexate, alternative co-therapies are needed. This method involved retrospective analysis of ten patients treated with a combination of rituximab and leflunomide. Primary outcome measures were the DAS28 response at month 6 and the time to relapse. The median initial DAS 28 of 5.7 (3.2-7.2) was reduced to 3.5 (1.9-6.1) at month 6. 70% of the patients achieved a good or moderate response, whereas 30% showed no response. Two patients had to stop leflunomide due to adverse effects. Two patients had to reduce the leflunomide dose to 10 mg/day. 5/8 patients experienced a relapse after a median of 10 (6-30) months and were successfully re-treated with rituximab. This small case series suggests that leflunomide might offer an alternative DMARD combination option for the treatment of RA with rituximab.

First-line DMARD choice in early rheumatoid arthritis--do prognostic factors play a role?

To examine if prognostic factors predict the choice of first DMARD for patients with RA. Details of 616 patients with early RA were collected from 16 centres in the UK Early Rheumatoid Arthritis Network (ERAN). Logistic regression was used to identify whether HAQ score, swollen joint count (SJC), nodules, RF, ESR, CRP and erosions on radiographs were associated with the choice of first DMARD treatment. Of 616 patients, 547 (88%) were started on a DMARD, 253 (46%) on MTX, 230 (42%) on SSZ, 47 (9%) on other DMARD monotherapies and 17 (3%) on combination DMARD therapy (CoT). SSZ was started less frequently in patients with positive RF (P = 0.018; OR 0.59; 95% CI 0.38, 0.91) and high SJC (P = 0.02; OR 0.95; 95% CI 0.91, 0.99). MTX was favoured in patients with high SJC (P = 0.002; OR 1.07; 95% CI 1.02, 1.11). Non-prescription of DMARDs was associated with old age (P = 0.02; OR 0.98; 95% CI 0.96, 0.99) and low HAQ score (P = 0.009; OR 0.80; 95% CI 0.68, 0.95). None of the variables predicted CoT. All other variables and the hospital where the patient was treated were not independently associated with the choice of DMARD. When choosing DMARD monotherapy in early RA, rheumatologists in ERAN seem to preferentially prescribe MTX for patients with a poor prognosis and SSZ for patients with good prognosis. No DMARDs were used in older patients or in those with a low HAQ.

A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis

We examined how combination DMARD therapies and TNF inhibitors therapies plus MTX (TNF/MTX) affect clinical and radiological outcomes compared with MTX monotherapy in early RA. We systematically searched EMBASE, PubMed and Ovid Medline for randomized controlled trials (RCTs) of combination therapy in early RA. We evaluated ACR responses, withdrawals for inefficacy and toxicity, HAQ and radiographic progression. Meta-analysis using Review Manager evaluated random effects odds ratios (ORs) and random effects weighted mean differences (WMDs) between treatments. A preliminary search identified 2029 citations; 15 were relevant RCTs (4200 randomized patients). Patients with active disease were enrolled. Compared with MTX monotherapy, both combination DMARDs and TNF/MTX increased ACR20-70 responses (OR 1.64-2.02 and 2.03-2.30, respectively), reduced withdrawals for inefficacy (OR 0.52 and 0.29), reduced HAQ (WMD -0.17 and -0.16) and reduced annual X-ray progression (WMD -1.20 and -0.84%). DMARD combinations increased withdrawals for toxicity (OR 2.69; there was no difference with TNF/MTX). The only head-to-head RCT showed comparable efficacy for combination DMARDs and TNF/MTX combinations. In early active RA, both combination DMARDs and TNF/MTX are more effective than MTX monotherapy. DMARD and TNF/MTX combinations had equal efficacy on ACR response, withdrawals for inefficacy, disability and erosive progression. There is an apparent advantage for TNF/MTX combinations in the effect on toxicity with fewer consequent patients. We conclude that there is strong evidence in favour of combination treatment for RA but there is still uncertainty about which regimen is preferable.

Aktualisiertes Therapieschema der Rheumatoiden Arthritis. Ergebnisse eines Konsensusprozesses deutscher Rheumatologen 2009

Das Therapieziel bei der Behandlung von Patienten mit neu diagnostizierter Rheumatoider Arthritis (RA) heisst heute komplette Remission. Dies bedeutet nicht nur eine Reduktion der klinischen Krankheitsaktivität auf einen DAS28 kleiner 2,6, sondern auch den Ausschluss einer klinisch stummen Restsynovitits und/oder radiologischen Progredienz von Erosionen durch Sonografie bzw. MRT. Wir berichten über einen Konsensusprozess deutscher Rheumatologen mit dem Ziel, ein praktisch einsetzbares Update für einen Therapiealgoritmus bei RA zu geben. Methotrexat bleibt danach das Primärtherapeutikum. Bei unzureichendem Effekt kann auf Leflunomid gewechselt oder eine Kombination vom Methotrexat mit konventionellen Basistherapeutika angewendet werden. Partielle Responder auf eine konventionelle Basistherapie sollten einen TNF-Antagonisten (Adalimumab, Etanercept, Infliximab; in Kürze auch Golimumab bzw. Certolizumab-Pegol). Bei unzureichendem Ansprechen auf einen TNF-Blocker kommen grundsätzlich vier Möglichkeiten in Frage: Einsatz eines zweiten TNF-Blockers (z. B. bei sog. Sekundärversagen) oder Wechsel auf den Anti-Interleukin6-Antagonisten Tozilizumab, den B-Zell Inhibitor Rituximab oder den Inhibitor der T-Zell-Kostimulation Abatacept. Die Auswahl der Therapeutika hängt von zahlreichen Einzelfaktoren ab und ist durch den Rheumatologen daher stets individuell gesteuert. Bei längerfristiger Remission sollte eine De-Eskalalation der Therapie erwogen werden.

Contemporary patterns of care and disease activity outcome in early rheumatoid arthritis: the ERAN cohort

To report from the Early Rheumatoid Arthritis Network (ERAN), time from symptom onset to start of therapy, treatment choices and disease outcome in early RA. Patients with newly diagnosed RA were prospectively enrolled from 19 centres in the UK and Eire. Standardized information was collected on case report forms at first presentation, 3-6 months, 1 yr and annually thereafter. The choice and intensity of drug treatment was left to the discretion of individual centres. A total of 808 patients were recruited between 2002 and 2007, with a mean follow-up of 16 (0-60) months. Of them, 62% fulfilled four or more ACR criteria for RA at first visit. The median time from onset of symptoms to referral to secondary care was 4 months [interquartile range (IQR) 2-9, n = 655] and to start of first DMARD 8 months (IQR 4-13, n = 638). DMARDs were prescribed in 97% of the patients, initially as monotherapy in 91%, and as combination therapy in 9%. The second DMARD (n = 220) was a switch to another as monotherapy in 52% and step-up to combination therapy in 48%. The proportions with a 28-joint disease activity score >5.1 at baseline and 3 yrs were 46 and 19%, >3.2 were 84 and 54% and <2.6 were 6 and 33%, respectively. Patients presenting with RA in ERAN do not receive DMARDs promptly, largely due to delays in referral to secondary care. Contemporary treatment practice is to start with DMARD monotherapy, and to use combination DMARDs as second-line therapy in approximately half of them. Over 3 yrs the proportion of patients continuing to have active disease remains high.

Rheumatoid arthritis patients who smoke have a higher need for DMARDs and feel worse, but they do not have more joint damage than non-smokers of the same serological group

To investigate the influence of smoking on disease activity, drug need and radiographic joint damage in RF-positive and -negative patients with early RA. Baseline and 3-yr follow-up data of 896 patients of an early RA cohort comprised clinical and radiographic parameters (Ratingen Score). Information about disease severity, treatment and smoking were obtained by questionnaires. Univariate and multivariate analyses were used to show the influence of smoking on drug use, ACR improvement and joint damage. Smokers and non-smokers were compared according to RF serology. Fifty per cent of the patients were never, 23% past and 27% current smokers. Current smokers were significantly more often RF-positive (71%) than past (66%) or never smokers (53%), but neither the RF-positive nor the RF-negative current smokers had higher 28-joint disease activity score (DAS28) or radiographic scores than never or past smokers. Within 3 yrs, current smokers had taken significantly more DMARD combinations or biologics. Non-smokers and those with <20 pack-years (PYs) had a 2-fold higher probability to reach ACR improvement than heavy smokers (>20 PYs). However, smokers did not differ in radiographic joint damage when compared with non-smokers of the same serological group. The higher use of DMARDs may indicate that smoking weakens the potency of anti-rheumatic drugs and/or is needed to control an otherwise higher disease activity. Since the risk of adverse events increases with the amount of drugs taken, this is another reason to persuade RA patients to quit smoking.

Anakinra in the treatment of rheumatoid arthritis and other IL-1-driven conditions

Fewer than 40% of newly diagnosed patients with rheumatoid arthritis (RA) reach remission with a combination of traditional DMARDs, and therefore new effective therapies are still needed. Proinflammatory cytokines, such as TNF-α and IL-1, are important pathogenetic mediators in RA and related conditions. Targeted therapies against these cytokines and downstream inflammatory mediators have greatly added to the therapeutic arsenal and brought new hope to patients in providing physicians with new effective treatment options. In this context, the current role for anakinra as a biological agent in treating RA or similar rheumatic conditions, based on data from clinical or observational studies, appears to be as a second-line drug or as an alternative to B-cell depletion after TNF-α blockade, especially for high-risk patients or patients who fail to respond to TNF-α blockade due to side-effects. On the other hand, the convincing findings seen in preferentially IL-1-driven diseases such as adult-onset Still’s di...

Long-term use of combination DMARDs did not sustain disease remissions, but delayed joint damage in early rheumatoid arthritis

Source Citation Korpela M, Laasonen L, Hannonen P, et al. Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumati...

HLA-DRB1 alleles in patients with rheumatoid arthritis

Objective. To examine the distribution of HLA-DRBI alleles frequency in pts (pts) with protracted rheumatoid arthritis in Russian population. Material and methods. 44 pts with RA (ACR criteria) with a mean age 53,7 yrs (30-72), a mean disease duration 13,6 yrs (5-31) were included. 95% of pts were taken a monotherapy or combination of DMARDs. Radiographic damage assessment in wrists and foots was examined by Larsen method. HLA- DRBI typing was performed using PCR method. 135 health donors were a control group. Results. 27 RA pts had HLA-DRB*04 alleles (45,5%) , in control - in 12,6 %, respectively (p<0,0005, OR=6,3). DRBI*04 positive pts were 24 RF(+), along 12 RF(-) pts DR4-positive were 7 pts (74% versus 58%). Radiographic destruction was equally severe both in DR4(+) pts anf DR4(-) pts, 92% and 71% respectively (NS). Retrospective analysis of determination of the influence of DMARD choice showed that Amimalarics were applied at the onset of disease. At the present time Methotrexate was frequently administered both in all pts (p<0,0012) and in 12 DR4(+) pts (44%) in comparison with 3 DR4(-) pts (18%), (NS). The DR(-) pts who had moderate joint damage were taken Sulphasalazine. Combination therapy with DMARD and steroids was used more active in pts with DRB1*04 (NS). HLA-DRBI*04 had an association with factor of beginning time of DMARDs therapy (r=0,32, p<0,04) and a functional activity (r=0,35, p<0,05). Conclusion. The previously results showed that RA in Russian population is associated with a high frequency of DRBI*04 alleles and low frequency of DRBI*07 which had a protective role for disease course. HLA-DRBI*04 possibly could be included in the list of prognostic factors of RA. Large prospective long-term investigations are needed for the determination of specific genetic markers at the onset of RA that may be valuable for predicting the disease severity and selecting appropriate therapy.

Evidence-based medicine and applying new therapies in general practice: wish and reality

In the last years some important therapies were introduced in the treatment of rheumatoid arthritis (RA), which represent a significant clinical advance. This concerns the introduction of TNF blockade with etanercept and inflixmab, the combination of DMARDs, leflunomide and the COX-2-specific inhibitors. In the year 2000 the restrictive social law in Germany, the collective and individual budgets for medicaments, did prevent a broader use of the very expensive therapy with TNF blockade. A rising number of international healthcare studies shows a profound potential for saving costs by improving the functional capacity (HAQ) in patients with RA. The biologicals and leflunomide have this potential. To realise the potential of reducing healthcare costs by an optimal therapy of RA some modification of the restrictive social law is necessary as well as the introduction of disease-management programs.

COMORBIDITY IN RHEUMATOID ARTHRITIS

It is increasingly clear that coexistent disease plays a pivotal role in RA outcome and that efforts aimed at specifically addressing these comorbidities need to be aggressively sought, investigated, and implemented once proven effective. RA-associated costs are currently increasing at twice the rate of the medical care index. Comorbidity in the setting of RA independently predicts disease-associated disability (a major cost component) and mortality, underscoring the need for a more comprehensive approach to RA, one that adequately addresses disease-specific comorbidities. At present, many primary and secondary preventative measures (Table 1) for RA-specific comorbidities remain largely unproved and require rigorous investigation in a randomized prospective fashion. Despite this ongoing need, advances are being made in our understanding of the underlying pathogenesis of these comorbid conditions and their relation with RA. This improved understanding should translate into further effective interventions. Bisphosphonates, for instance, have been shown to be effective in the prevention of GIOP and associated fractures. The past several years have seen other exciting therapeutic advances in RA. DMARD combinations have been shown to be more effective and no more toxic than MTX monotherapy. In addition to the recent release of COX-2 NSAIDs, three new disease-modifying agents (leflunomide, etanercept, and infliximab) have been added to the therapeutic armamentarium; these are options that have markedly changed the treatment landscape in RA. Although these important advances have generated much deserved optimism, the precise effect that these agents may have on RA-specific comorbidity remains to be seen. The next decade should prove to be an exciting time in RA management. Better identification, understanding, and management of RA comorbidities have great potential to improve quality of life and survival among our patients with RA.

Le traitement de la polyarthrite rhumatoïde. Évolution des idées et des stratégies

Treatment of rheumatoid arthritis. Evolution of concepts and strategies. Introduction. — The treatment of rheumatoid arthritis includes non-steroid anti-inflammatory drugs (NSAID), low-dose steroids and drugs which modify the evolution of the disease (disease modifying anti-rheumatic drugs, [DMARD]). In the last few years, the long-term efficiency of the recommended treatment strategies in rheumatoid arthritis has been a matter of debate and their basic assumptions have been challenged. Numerous studies were undertaken to settle the question. They tried to delineate the rules for an optimal use of current drugs and other therapeutic means. Current knowledge and key points. — Rheumatoid arthritis is a crippling disease. It decreases life expectancy and irreversible bone and joint damage may develop even in the first months of evolution. The sooner the prescription of DMARD, the higher the frequency and quality of rheumatoid arthritis improvement and, in the long-term, the lesser the functional impairment. Low dose steroids, when administered early, can slow down the development of radiologic lesions. Some of their effects are thus closer to those of DMARD than to those of symptomatic treatment. NSAID are at least as equally dangerous as DMARD and possibly more so in terms of the potential number of severe side effects. The combination of several DMARD does not increase their overall toxicity. An evaluation of the most efficient combinations and of the clinical situations in which combinations show promise of improved results is in progress. Future prospects and projects. — At present, the tendency is to treat early and intensively, in order to obtain complete remission, improve evolution and reduce functional impairment. This strategy requires early diagnosis and early evaluation of prognosis of rheumatoid arthritis. Rheumatoid arthritis with benign evolution would not warrant intensive treatment. Studies are in progress to evaluate the prognostic factors in early rheumatoid arthritis that would enable us to adapt the strength of initial treatment to the disease's putative severity.

TRIPLE THERAPY WITH METHOTREXATE, SULFASALAZINE, AND HYDROXYCHLOROQUINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Combinations of DMARDs are currently used to treat rheumatoid arthritis by almost all rheumatologists. This article reviews the published data on the triple combination of methotrexate, sulfasalazine, and hydroxychloroquine, discusses caveats for clinical use, compares efficacy of different combinations, and speculates on future combination therapies.