Conventional disease-modifying antirheumatic drugs in early arthritis

This article reviews the use of conventional disease-modifying antirheumatic drugs (DMARDs) in the treatment of early rheumatoid arthritis (RA). The Finnish early RA cohorts are used as examples of how early and active treatment strategies have improved over time with increasing variety of available DMARDs. Therapy goals of early RA include remission to prevent severe long-term outcomes of RA. Remission can be achieved in a third of patients with early RA using a combination of conventional DMARDs, including methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone. Of patients with early RA, 20% to 30% do not improve enough with conventional treatments and should be identified at early phases to consider institution of biologic agents.     

Value of dual-energy x-ray absorptiometry as a diagnostic and assessment tool in early rheumatoid arthritis

New research has revealed common pathophysiologic and cellular mechanisms behind the development of osteoporosis and joint damage in rheumatoid arthritis (RA). Because osteoporosis is a direct consequence of the inflammatory disease process, bone mass measurements in principle could be an outcome marker of inflammation, of damage, and of response to therapeutic intervention. Several devices have been developed for quantitative bone mass assessment including dual energy x-ray absorptiometry (DXA), which is considered the reference standard. This article based on current data and understanding discusses the use of DXA as a diagnostic and assessment tool especially in early RA.     

Imaging in early arthritis

Imaging can play a vital role in the evaluation of patients with early arthritis. Various imaging methods can be utilized to aid with diagnosis, predict prognosis and follow disease progression and treatment response. Previously, conventional radiography was the principal method used to evaluate and follow bone damage in patients with inflammatory arthritis. More recently the use of magnetic resonance imaging and ultrasonography has gained wider acceptance and popularity due to the ability of these multiplanar techniques to image both bone changes and soft tissue abnormalities, including synovitis. This chapter discusses the current imaging modalities used in the evaluation of patients with early arthritis, as well as the use of imaging in establishing the extent of disease, in prognosis and in monitoring disease course. Current data on imaging of patients with early arthritis due to rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis is reviewed.     

Conventional therapy of psoriatic arthritis: evidence-based review

Psoriatic arthritis is a heterogeneous condition, the pattern of which is determined by any combination of pathology affecting peripheral joints, the enthesis and the spine. There is a paucity of evidence for most of the conventional agents used to treat psoriatic arthritis, with many of them being used on the basis of experience in rheumatoid arthritis. Herein, we summarise the evidence compiled relating to effectiveness of treatment for various manifestation of PsA. For those patients with progressive forms of arthritis who may benefit from intervention of newer biological therapies, the continued use of conventional therapy needs ever increasing scrutiny.     

Azathioprine in early rheumatoid arthritis

This study compares the effect of azathioprine with those of gold and chloroquine in early (Class II) rheumatoid arthritis (RA). Thirty-three similar patients with classic or definite RA of less than 5 years duration were randomly entered, 11 into each drug group. Assessment of standard clinical and laboratory measures at 12 and 24 weeks showed significant improvement in all three groups. In general, all three drugs were effective antirheumatic agents with low toxicity. However, because of serious potential toxicity, azathioprine could not be recommended over gold and chloroquine in early RA therapy.     

Imaging in early rheumatoid arthritis

Imaging in early rheumatoid arthritis (RA) has undergone extraordinary change in recent years and new techniques are now available to help the clinician diagnose and manage patients much more effectively than previously. While established modalities such as plain radiography (X-Ray) remain important, especially for detection of erosions and determining the progression of joint damage, there are many instances where ultrasound (US), magnetic resonance imaging (MRI) and computed tomography (CT) scanning provide added information. MRI and US are now used regularly by clinicians to help diagnose RA in the pre-radiographic stage as they offer improved visualisation of joint erosions. They also have the potential to provide prognostic information as MRI bone oedema/osteitis is linked to the later development of erosions and power Doppler ultrasound (PDUS) joint positivity is also a predictor of joint damage. Nuclear imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) are also highly sensitive for detecting joint change in early RA and pre-RA but not yet used clinically mainly because of accessibility and radiation exposure. MRI, US, scintigraphy, SPECT and PET have all been shown to detect sub-clinical joint inflammation in patients in clinical remission, a state that is now the goal of most treat-to-target management strategies. Thus, imaging may be used to direct therapeutic decision making and MRI is also now being used in clinical trials to determine the impact of disease-suppressing therapy on the course of synovitis and osteitis. As is the case for all tests, it would be unwise to rely completely on any one imaging result, as false positives and negatives can occur for all modalities. Thus, the clinician needs to choose the most relevant and reliable imaging test, while also striving to minimise patient discomfort, radiation burden and economic impact.     

Biologics in early rheumatoid arthritis

Treatment of patients with rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs is started immediately after diagnosis, resulting in more effective suppression of disease activity and substantial reduction of joint damage. The development of biologic agents has enabled remission as a realistic therapeutic goal in a greater proportion of patients. The tumor necrosis factor-alpha inhibitors, infliximab, etanercept, and adalimumab, have been studied in numerous randomized clinical trials. These agents can suppress disease activity directly, slow or stop progression of radiologic damage, and prevent further loss of quality of life. Patients treated with tumor necrosis factor-alpha inhibitors show few adverse events, which together with the high clinical effectiveness is favorable for treatment compliance. The exact role of these agents in the treatment of early-stage RA is unknown.     

Measurement of periarticular bone mineral density in the hands of patients with early inflammatory arthritis using dual energy x-ray absorptiometry

Hand bone densitometry is more sensitive than standard radiology in the measurement of disease-related bone damage in early arthritis. Most studies employing dual energy x-ray absorptiometry (DXA) have evaluated the whole hand. The aim of this study was to evaluate a method that quantified bone density in regions of interest that were confined to the juxta-articular areas of metacarpo-phalangeal (MCP) and proximal interphalangeal (PIP) joints. Patients with inflammatory arthritis affecting the hands were selected for study. Postero-anterior (PA) scans of selected juxta-articular sub-regions were acquired using a Hologic 4500 Elite bone densitometer and forearm software. Each hand was scanned three times in immediate succession with repositioning between scans. The six selected sub-regions included the periarticular regions of the second, third, and fourth MCP and PIP joints. Sub-regions of different dimensions (4 and 5 mm proximal and distal to the joint space) were assessed at each joint. Coefficients of variation (CV) were calculated for bone mineral density (BMD) and bone mineral content (BMC) of each selected sub-region. Eighty four individual hand joints in seven patients were evaluated three times. Precision values ranged between 0.89% and 2.37% for BMD and between 1.38 and 3.26 for BMC measurements. BMD measurements of MCP joints were more precise than PIP joints. BMD measurements of 10-mm sub-regions were more precise than 8-mm sub-regions. The precision value for the net average BMD measurement of the six sub-regions evaluated was 0.78% for 8-mm sub-regions and 0.73% for 10-mm sub-regions. Net average BMC measurements had CV values of 1.11% and 1.08%, respectively. DXA can be used to reliably measure periarticular BMD and BMC of small joints in the hands in patients with early inflammatory arthritis. Precision values for quantifying juxta-articular bone approximated BMD measurements of the spine.     

Influence of x-ray treatment on antigen-induced experimental arthritis.

Six groups of 3 rabbits each were immunised with ovalbumin and received one intra-articular injection of antigen. The animals of 3 groups received local x-ray irradiation of 600 rads for 8 minutes to the right knee joint 12 days after the intra-articular challenge. Animals of the other 3 groups were not irradiated. The antigen-induced arthritis was investigated by determining the exudation is synovial fluid and by histological study of the synovium examined 48 hours, 7 days, and 4 weeks after the irradiation date. All animals in the nonirradiated groups showed a distinct chronic synovitis. Irradiated animals showed almost no synovitis 48 hours and 7 days following irradiation. In 2 rabbits synovitis had reappeared 4 weeks after irradiation with findings similar to those in the control groups. Only one animal still showed an inhibition of synovitis. X-ray irradiation of non-challenged knees did not induce any pathological changes. This time-limited effect of one local irradiation on antigen-induced arthritis seems to be mainly an anti-inflammatory action. Local immunological inhibition might possibly operate too. X-ray induced inhibition of synovitis is compared with the effect of locally injected radiocolloids.     

Prognostic factors in early rheumatoid arthritis

The current paradigm for rheumatoid arthritis suggests that persistent synovitis leads to erosive joint damage, progression of which results in functional disability. Studies of X-ray progression followed for 1-9 yr have shown that 40-83% of subsequent progression can be predicted by a combination of prognostic factors such as joint involvement, high levels of C-reactive protein and rheumatoid factor (RF) positivity. There are similar findings for predictors of functional disability in studies followed for 2-15 yr. The most consistent prognostic feature is RF positivity, which is equally important in predicting joint damage and functional disability. Immunoglobulin A RF and the co-presence of RF with anti-keratin or anti-filaggrin antibodies may increase levels of prediction. Added value of genetic predictors over that of RF remains inconclusive. Therefore, therapeutic management should be individualized. Cases with active disease and seropositive RF tests merit aggressive therapy; conversely, cases with little synovitis and seronegative tests require conservative management.     

Therapeutic strategies in early rheumatoid arthritis

Rheumatoid arthritis (RA) therapy rests primarily on the use of disease-modifying antirheumatic drugs (DMARDs). It has been unequivocally shown that DMARD therapy early in the course of RA retards progression of damage and disability to a larger degree compared with delayed institution; the most effective DMARD is methotrexate (MTX). Moreover, combination therapy including intermediate to high doses of glucocorticoids and combinations of MTX with tumour necrosis factor blockers are more effective than monotherapies. However, early DMARD treatment requires early referral of patients and early diagnosis. This is hampered by the current lack of classification criteria for early RA, since the aim is to prevent destruction from occurring, while RA is typically characterized by the presence of erosions. Novel treatment strategies and therapeutic agents allow us to aim for remission rather than improvement of disease activity. Whether a 'window of opportunity' exists during which effective therapy might lead to cure is still an open issue and will be the focus of clinical trials in the near future.     

Infliximab in active early rheumatoid arthritis

Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA).     

Bone changes in early rheumatoid arthritis

Bone disease in rheumatoid arthritis affects the peri-articular and axial skeleton and is a major cause of disability. Recent studies have shown that pro-inflammatory cytokines stimulate the expression of osteoprotegerin ligand, a transmembrane protein of the tumour necrosis factor ligand superfamily, on synoviocytes and activated T cells. Osteoprotegerin ligand stimulates osteoclast formation and activation, membrane-bound and soluble osteoprotegerin ligand leading to osteoporosis as well as erosions. Bone densitometry using dual energy X-ray absorptiometry is an objective and precise method for monitoring this bone disease. Bone loss is more rapid in patients with early rheumatoid arthritis and correlates well with measures of inflammation and function. Data are emerging that monitoring bone loss of the hands in early rheumatoid arthritis could be an outcome measure and a prognostic indicator of future functional disability. Suppressing inflammation effectively and the use of bone active agents can reduce the rate of loss. In animal models, osteoprotegerin-a decoy receptor of osteoprotegerin ligand-blocks osteoporosis and erosions without affecting inflammation. The use of new biological agents could in future effectively prevent and treat rheumatoid bone disease.     

Antifilaggrin autoantibodies in early rheumatoid arthritis

OBJECTIVE: To study antifilaggrin autoantibodies in patients with early rheumatoid arthritis. METHODS: Antifilaggrin autoantibodies were detected by immunoblotting (AFA) and by indirect immunofluorescence ('AKA') in sera from 112 patients with early RA. RESULTS: At baseline, 'AKA' were detected in 29% and AFA in 32% of sera, whereas after 12 months, they were present in 23% and 26% of sera, respectively. Significant associations between 'AKA', AFA, and rheumatoid factor were found. 'AKA' and AFA titres were significantly higher in patients with susceptibility alleles. No clear relation was observed between 'AKA', AFA, and disease activity but radiological progression tended to be more pronounced in patients having antifilaggrin autoantibodies. CONCLUSIONS: Antifilaggrin autoantibodies, being present in about one third of all new cases of RA, may have a value in early diagnosis. The present data suggest that these autoantibodies also may be a marker of disease severity.