Early RA
Factors That Predict Outcome
Abstract #294 In Early Rheumatoid Arthritis, Presence of Inflammation in Individual Hand Joints Predicts (Progression of) Damage in That Joint. M Boers, P Kostense, COBRA Trial Group. The Netherlands.
These investigators asked whether the presence of inflammation in an individual joint would predict radiologic damage in that joint. Patients enrolled in the COBRA multicenter study (Lancet 1997) were studied. Radiographs of the hand MCPs and PIPs in 135 patients were evaluated and compared at baseline and at one year followup. At baseline, 6% of the MCPs and PIPs showed radiographic damage, and 10% of joints progressed. The presence at baseline of damage, swelling or pain in a joint independently and strongly predicted progression of the total Sharp (radiological) score in that joint (p<.001). Each additional swelling point tripled the risk for subsequent damage progression. MCPs were more than 4 times more likely to develop narrowing than PIPs.
Editorial Comment: There has been controversy as to whether inflammation and radiographic joint damage are closely correlated. The current study was undertaken to study the relationship between the two, and confirmed a strong relationship between the presence of inflammation in an individual joint and eventual damage in the same joint.
Abstract #1893 Early Treatment of Inflammatory Polyarthritis Reduces Disability at Five Years: Results From a Large Observational Cohort Using Propensity Scores to Adjust for Disease Severity N Wiles, G Dunn, M Lunt, E Barrett, M Bukhari, A Silman, D Symmons. United Kingdom
A number of therapies have been shown to be effective in RA in short-term trials, but there are few studies that examine the effect of therapies on long-term disability. In observational studies, comparison of outcomes of treated versus untreated patients may be misleading because patients with more severe disease are likely to be treated. Propensity scores have been proposed as a method to adjust for this bias in treatment assignment. The aim of this study, therefore, was to determine the effect of treatment with DMARDs and/or steroids on 5 year disability outcomes in patients with inflammatory polyarthritis. 384 patients registered by the Norfolk Arthritis Register were followed for five years, and treatment details and Health Assessment Questionnaire (HAQ) scores were recorded annually. Results: Unadjusted analysis suggested that patients who received treatment had an increased odds ratio of a worse outcome compared to untreated patients. However, when adjusted for differences in disease severity, using the propensity score, early treatment (within 6 months of symptom onset) was associated with a similar odds of disability at five years compared to those not treated (OR: 0.71 (0.34, 1.44). In contrast, starting treatment later (> 6 months) was associated with a 2-fold increased odds of having a HAQ > 1.00 at five years. This study shows that early treatment with DMARDs/steroids reduced the odds of disability five years later to a level comparable with those judged clinically not to require treatment.
Editorial Comment:The goal of treatment of RA is to prevent disability. Studies such as this one that attempts to evaluate the efficacy of treatments for preventing disability are very important. This study is consistent with the increasingly accepted tenet to treat RA early.
Therapy
Abstract #1891 Legacy of COBRA Combination therapy: Gain in Damage Control is Probably Permanent R Landewe, M Boers, A Verhoeven, The COBRA Study Group. The Netherlands.
In a previous report (Lancet 1997), combination therapy known as COBRA (prednisolone stopped after 6 months, low-dose methotrexate stopped after 7 months, and sulfasalazine (SSZ) maintenance therapy) was more effective than SSZ monotherapy in inhibiting radiological progression of RA at 18 months. The current study was undertaken to determine whether the radiological benefits of COBRA therapy could be sustained. At the end of the original COBRA trial, patients were followed by their rheumatologists and no treatment protocol was specified. Patients were followed for a mean of 4 years. At least 3 films of hands and feet were available for 94% of patients. Xrays were scored according to the Sharp/vander Heijde method. Results: The rate of radiological progression during the followup period was statistically significantly lower in the original COBRA group than in the original SSZ group.
Editorial Comment: These data confirm that early treatment of RA can have significant benefits radiologically that can be sustained over a long period of time.
Abstract #1892 High Dose Oral Methotrexate (MTX) in Early RA is Needed for Maximum Efficacy M Genovese, E Keystone, J Tesser, B Finck and G Spencer-Green. Arizona and Washington.
Previous studies have suggested that higher doses of MTX are more effective in treatment of RA but no prospective study has been done. In a study of early RA comparing etanercept to MTX (see 1999 ACR Meeting Highlights), 217 patients were treated with MTX thus allowing a post-hoc analysis of MTX efficacy by dosage. The cumulative dose of MTX over one year was calculated for all patients and the lowest quartile (MTX < 800 mg/year or approximately < 15 mg/wk; 54 patients) was compared to the highest 3 quartiles (MTX > 800 mg/year or approximately > 15 mg/wk; 163 patients). Results: Clinical improvement was better over 12 months for those in the high MTX quartiles compared to the low MTX quartile (AUC of ACR-N 31 vs 20, p<.001; HAQ AUC 0.4 vs 0.6, p<.001). More patients receiving high dose MTX had no radiographic progression by total Sharp score over one year (61% vs 46%, p = .041).
Editorial Comment: Although a post-hoc analysis, these data suggest that we should be pushing MTX to weekly doses of > 15 mg routinely in our patients unless tolerability/adverse events limit use of these higher doses.
Abstract #1894 Early Sero-Positive Rheumatoid Arthritis (RA) Treatment: A 2-Year, Double-Blind Comparison of Minocycline and Hydroxychloroquine (HCQ) ODell, K. Blakely, J Mallek, P Eckhoff, R Leff, S Wees, K Sems, A fernandez, W Palmer, L Klassen, G Paulsen, C Haire, G Moore. Nebraska.
Minocycline has been reported to be superior to placebo in treating early RA (Arthritis Rheum 40:842-8, 1997). This study was designed to determine whether minocycline was superior to hydroxychloroquine (Plaquenil®) for the treatment of early RA. Early RA was defined by disease of < 1 year duration and RF positivity. Patients were treated with minocycline 100 mg bid or HCQ 200 mg bid in a randomized, double-blind, 2-year trial. All were started on prednisone 5 or 7.5 mg/d (depending on weight). Prednisone was tapered after 6 months based on pre-set criteria. Primary endpoints with ACR20 response and mean prednisone dose at 2 years. Results: Minocycline-treated patients had higher ACR20 and ACR50 responses, and were on less prednisone at 2 years, than hydroxychloroquine-treated patients. Both drugs were well tolerated.
Editorial Comment: Minocycline performed surprisingly well, although the ACR20 responses were not statistically different between the minocycline and hydroxychloroquine groups (63% vs 39%, p .07). No Xray data or ESR data were presented. Since the mechanism of minocycline remains unclear but may work as an anti-inflammatory by inhibiting metalloprotease enzymes, it would have been interesting to know the relative potency of minocycline versus hydroxychloroquine for reducing ESR and preventing structural damage (assessed by xrays).
Abstract #1896 Combination Therapy With Cyclosporin-A (CsA) and Methotrexate (MTX in Patients with Early Aggressive Rheumatoid Arthritis (RA), A Randomized Double Blind Placebo Controlled Trial. A Gerards, R Landewe, A Prins, G Bruijn, The HS Goei, B Dijkmans. Holland.
In patients with advanced RA who have had an inadequate responses to MTX alone, CsA adds additional benefit. However, MTX + CsA has not been compared prospectively to CsA alone, nor has the combination been evaluated in patients with early RA. In this prospective double-blind randomized trial, patients with RA for < 3 years who were RF positive or had erosions on xrays were randomized to treatment with MTX + CsA or to CsA + placebo. Results: ACR20 and 70 responses were not different between the two groups. ACR50 response rates were higher in the CsA + MTX group compared to CsA alone (47% vs 19%, p.004).
These results are difficult to interpret. A more useful study would have been to compare CsA + MTX versus MTX alone, since MTX is the first line of treatment for RA, at least in the U.S.
