Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study.

OBJECTIVE: To investigate whether clinical and radiographic disease control can be achieved and maintained in patients with early, active rheumatoid arthritis (RA) during the second year of aggressive treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and intra-articular corticosteroid. This paper presents the results of the second year of the randomised, controlled double-blind CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) study. METHODS: 160 patients with early RA (duration <6 months) were randomised to receive intra-articular betamethasone in any swollen joint in combination with step-up treatment with either methotrexate and placebo-ciclosporine (monotherapy) or methotrexate plus ciclosporine (combination therapy) during the first 76 weeks. At week 68 hydroxychlorochine 200 mg daily was added. From week 76-104 ciclosporine/placebo-ciclosporine was tapered to zero. RESULTS: American College of Rheumatology 20% improvement (ACR20), ACR50 and ACR70 levels were achieved in 88%, 79% and 59% of patients in the combination vs 72%, 62% and 54% in the monotherapy group (p = 0.03, 0.02 and 0.6 between groups). The patients globally declined from 50 to 12 vs 52 to 9, with 51% and 50% in Disease Activity Score (DAS) remission, respectively. Mean (SD) progressions in total Sharp-van der Heijde scores were 1.42 (3.52) and 2.03 (5.86) in combination and monotherapy groups, respectively (not significant). Serum creatinine levels increased by 7% in the combination group (4% in monotherapy), but hypertension was not more prevalent. CONCLUSION: Continuous methotrexate and intra-articular corticosteroid treatment resulted in excellent clinical response and disease control at 2 years, and the radiographic erosive progression was minimal. Addition of ciclosporine during the first 76 weeks resulted in significantly better ACR20 and ACR50 responses, but did not have any additional effect on remission rate and radiographic outcome.

MRI abnormalities of sacroiliac joints in early spondylarthropathy: a 1-year follow-up study.

OBJECTIVE: To describe changes in chronic and acute magnetic resonance imaging (MRI) abnormalities of the sacroiliac joints (SIJs) in early spondylarthropathy (SpA), and to associate these findings with computed tomography (CT), X-ray, and clinical findings during a 1-year follow-up. METHODS: Thirty-four patients, 20 males and 14 females, median age 27 years, with inflammatory low back pain (median 23 months) were included. MRI, CT, and X-ray, as well as clinical and laboratory tests were performed. After a follow-up period of 1 year (median 377 days) the examinations were repeated, and the findings were correlated. RESULTS: MRI and CT changes resulting from SIJ destruction increased significantly during follow-up, and the two modalities were significantly correlated. For the MRI findings of inflammatory activity, only bone marrow oedema decreased significantly. An increase in the Schober test was the only clinical examination that changed significantly. CONCLUSION: In early SpA, MRI can detect significant inflammatory and destructive changes of the SIJs over a 1-year follow-up period, in spite of minimal changes in the clinical parameters. The MRI changes in inflammatory activity are not detectable by CT and X-ray examinations. Thus, MRI may be a sensitive method, without known risks, for early diagnosis and for following disease progression in SpA.

Magnetic resonance imaging of sacroiliitis in early seronegative spondylarthropathy. Abnormalities correlated to clinical and laboratory findings.

OBJECTIVE: To compare a new MRI scoring system of the sacroiliac joints (SIJs) in early spondylarthropathy (SpA) with clinical and laboratory parameters. METHODS: Forty-one patients (24 males, 17 females) with a median age of 26 yr and a median duration of inflammatory low back pain of 19 months were included. They all fulfilled the ESSG-criteria for SpA. The patients were examined by MRI of the SIJs using a new scoring system. Clinical examinations, biochemical tests, functional score (BASFI), and pain score (BASDAI) were also performed. RESULTS: 95% of the patients had inflammation and/or destructive bone changes of the SIJs at MRI. No correlation was found between MRI pathology and clinical findings. MRI demonstrated significantly greater severity of both inflammation and destruction of the SIJs in HLA B27 positive patients than in the HLA B27 negative patients. CONCLUSIONS: In patients with early SpA, MRI was able to detect inflammatory and destructive changes of the SIJs, but the changes were not associated to clinical findings. Our results suggest a role of MRI in the detection of early-stage sacroiliitis.

Prospectively measured red cell folate levels in methotrexate treated patients with rheumatoid arthritis: relation to withdrawal and side effects.

OBJECTIVE: To investigate whether red cell folate (RCF) levels relate to side effects, withdrawals, or disease activity during treatment with the folic acid antagonist methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: Side effects were recorded monthly, RCF levels were measured by lactoglobulin binding radioassays, and 8 variables for disease activity were measured in a placebo controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n = 23) and D-penicillamine (n = 23). RESULTS: From Week 20 RCF levels decreased only in the MTX group (p < 0.02), and 5 MTX treated patients withdrew due to side effects. Withdrawals had lower RCF values at Weeks 0 and 9 compared to the remaining patients (p < 0.05). Folate deficiency evolved in 5 patients; 2 of these developed cytopenia. Aberrations in the scheduled dosage increase were related to lower pretreatment values of RCF (p = 0.007). Side effect scores were inversely correlated to RCF values at Weeks 0, 9, and 28 (p < 0.05). RCF levels measured concomitantly with liver enzyme elevation were lower than the remaining values (p < 0.001). When side effects were reported, 96% of concomitantly measured RCF values were below 800 nmol/l. RCF values at entry did not correlate to improvement in any variable for disease activity, or a graded overall improvement. CONCLUSION: RCF levels decrease during MTX treatment and relate to side effects, withdrawals, liver enzyme elevations and aberrant MTX dosage increase, but not to the therapeutic effect. RCF above 800 nmol/l protects against side effects.

Nutritional status of Danish rheumatoid arthritis patients and effects of a diet adjusted in energy intake, fish-meal, and antioxidants.

This study deals with the nutritional status of Danish RA patients and address the question of whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of 6 months duration, 109 patients with active RA were randomly assigned to either treatment with or without a specialized diet. The energy consumption was adjusted to normal standards of body weights and the intake of fish meals and antioxidants were increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, number of swollen joints, pain status, and reduced cost of medicine, while doctors global assessment, laboratory data, X-ray, and daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.