Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation.

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y. Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187 SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2-11% of the patients, seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the disease course in most patients was characterized by periods of tiredness (42-60%), arthritis (20-25%), skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%) and leucopenia (17-19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.

Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT).

OBJECTIVE: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE. METHODS: Outcome parameters were the ACR criteria, the SLE disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM) and the requirement for treatment. In 10 European rheumatology centres, patients who had been evaluated in the last 3 months of 1994 and had been diagnosed as having incomplete SLE on clinical grounds for at least 1 yr were included in the study. All 122 patients who were included in the study were evaluated annually during 3 yr of follow-up. RESULTS: Our results are confined to a patient cohort defined by disease duration of at least 1 yr, being under clinical care at the different centres in Europe. These patients showed disease activity that was related mostly to symptoms of the skin and the musculoskeletal system, and leucocytopenia. During the follow-up, low doses of prednisolone were still being prescribed in 43% of the patients. On recruitment to the study, 22 of the 122 incomplete SLE patients already fulfilled the ACR criteria for the diagnosis of SLE. In the 3 yr of follow-up only three patients developed SLE. CONCLUSIONS: A high proportion of patients in our cohort defined on clinical grounds as having incomplete SLE eventually showed disease activity defined by the SLEDAI as well as ECLAM. However, only three cases developed to SLE during the follow-up. This suggests that incomplete SLE forms a subgroup of SLE that has a good prognosis.

Systemic lupus erythematosus: clinical features in patients with a disease duration of over 10 years, first evaluation.

OBJECTIVE: Most information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first 5 yr after disease onset. Data about the disease course 10 yr after disease onset are rare. The aim of this multicentre study was to describe the outcome of SLE patients with a disease duration of >10 yr. METHODS: Outcome parameters were the SLE Disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR), a global damage index (DI) and required treatment. In 10 different European rheumatology centres, all SLE patients who were evaluated in the last 3 months of 1994, and who had been diagnosed with SLE at least 10 yr ago, were included in the study. RESULTS: It should be stressed that our results are confined to a patient cohort, defined by a disease duration of at least 10 yr, and who are still under clinical care at the different centres in Europe. These SLE patients still showed some disease activity, related to symptoms of the skin and musculoskeletal systems, next to the presence of renal involvement. A total of 72% of the patients needed treatment with prednisolone (

Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.

OBJECTIVE: To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). METHODS: Patients with active and severe RA (disease duration <8 years) were recruited into a 24-week, double-blind, randomized, placebo-controlled, multicenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (< or =10 mg prednisolone daily) remained constant throughout the study. Any disease-modifying antirheumatic drugs that were being administered were discontinued at least 6 weeks prior to enrollment. Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. RESULTS: A total of 472 patients were recruited. At enrollment, the mean age, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical parameters of disease activity were similar in each treatment group and were consistent with active and severe RA. At 24 weeks, of the patients who received 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criteria for response (the primary efficacy measure), 44% met the Paulus criteria, and statistically significant improvements were seen in the number of swollen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnaire score, C-reactive protein level, and erythrocyte sedimentation rate. In addition, the rate of radiologic progression in the patients receiving IL-1Ra was significantly less than in the placebo group at 24 weeks, as evidenced by the Larsen score and the erosive joint count. IL-1Ra was well tolerated and no serious adverse events were observed. An injection-site reaction was the most frequently observed adverse event, and this resulted in a 5% rate of withdrawal from the study among those receiving IL-1Ra at 150 mg/day. CONCLUSION: This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion.

Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study.

OBJECTIVE: To assess the safety and effectiveness of leflunomide versus placebo in patients with active rheumatoid arthritis (RA) treated for 6 months. METHODS: Four hundred two patients were randomly assigned to receive placebo or leflunomide at 5 mg, 10 mg, or 25 mg daily. A washout period of 6-12 weeks from prior second-line therapy was required. RESULTS: Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10-mg and 25-mg dosage groups compared to placebo. Twenty-one patients (7.0%) in the active treatment groups withdrew due to adverse events (AEs). The incidence of AEs was higher with leflunomide than with placebo. Gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia were more common in the 10-mg and 25-mg dosage groups. The incidence of infections was similar between the treatment and placebo groups; no opportunistic infections were seen. Transient elevations in liver function studies were noted in a small number of patients. CONCLUSION: Leflunomide is effective in daily doses of 10 mg and 25 mg in patients with active RA. Improved efficacy at the 25-mg dose was associated with a higher incidence of AEs. Randomized, placebo-controlled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.

Cervicobrachial syndrome--work and disability.

The subjects in the study were 114 persons receiving a disability pension or referred for disability assessment. They were placed in two groups of 57 persons each, one with marked cervicobrachial syndrome and the other without. The latter group was chosen by the method of equivalent pairs with regard to sex and age. All subjects underwent a clinical examination and a standardized questionnaire was completed. The questionnaire pertained to the state of health, focussing on the amount and type of physical burdening at the workplace and on activities outside the workplace. Sixty-five percent of the subjects were aged from 51 to 60 years. A statistically significant difference was established between earlier occupation and cervicobrachial syndrome. Cervicobrachial syndrome was found in 31.6% of unskilled workers and 12.3% of the controls (P < 0.05). A forced body posture during work was recorded in 74% of the subjects with the syndrome and in 50% of the control subjects (P < 0.05). Repetitive movements at work were reported by a large number of subjects with cervicobrachial syndrome (71.9:49.1%; P < 0.05) who also claimed to strain the arms (84.2:61.4%; P < 0.05) and burden the cervical spine (68.5:40.4%; P < 0.05) during household activities to a significantly greater extent than the controls. A possible preventive approach to the occurrence and progression of cervicobrachial syndrome is discussed.

A double-blind trial of ademetionine vs naproxen in activated gonarthrosis.

The efficacy and safety of ademetionine (A) vs naproxen (N) were tested in a double-blind trial carried out in 20 patients, each with activated gonarthrosis. The trial lasted 6 weeks. During the first week, A was administered at a daily dose of 3 x 400 mg and afterwards at a dose of 2 x 400 mg, whereas the daily dose of N during the first week was 3 x 250 mg and subsequently 2 x 250 mg. During the first two weeks, the patients were allowed to take paracetamol as an additional analgesic. The patients were examined at the beginning of the study and after 2, 4 and 6 weeks. The parameters tested were: pain (under different conditions), crepitation, joint swelling, circumference of joint, extent of motility and walking time over 10 meters. In addition to the usual laboratory tests, the serum keratane-sulphate concentrations (with monoclonal antibodies according to the ELISA technique of Eugene et al. [1985]) were also determined. At the end of the 6th week no statistically significant difference between the two patient groups treated was found; both groups exhibited a marked improvement on all parameters. At the end of medication, the keratane-sulphate concentrations were not significantly changed. Five patients under A and 3 under N reported gastrointestinal side effects which were possibly drug-related. This study, performed in a small number of patients, showed a good efficacy and safety of ademetionine. Only further studies on a larger scale will show the importance of ademetionine in the therapy of rheumatic diseases.

[The value of individual laboratory tests in the evaluation of inflammatory activity in rheumatoid arthritis]. / Vrijednost pojedinih laboratorijskih testova u ocjeni upalne aktivnosti reumatoidnog artritisa.

In 65 patients with definite or classical rheumatoid arthritis (RA), according to ARA criteria, and the active disease, we studied the correlation of the clinical status (the number of the swollen and tender joints) with the following laboratory parameters: sedimentation rate, C-reactive protein, serum iron level, haemoglobin content and the number of erythrocytes, leucocytes and thrombocytes in the peripheral blood. All patients received nonsteroidal antiinflammatory drugs; 25,5% of them were on small daily doses of corticosteroids, and most of them (76,5%) were receiving some of the second-line drugs. The acceleration of the sedimentation rate was the most useful laboratory parameter and was found in 96,9% of the patients, followed by an increased quantity of the alpha-2 globulin, sideropenia and a decreased level of haemoglobin. Increase in the CRP titer was found in this study to be of a rather modest value and was increased in only 40% of the RA patients.

Effect of imaging time on the values of the sacroiliac index.

Quantitative scintigraphy of the sacroiliac joints was performed in a group of normal subjects and a group of subjects with unilateral and bilateral sacroiliitis. The aim of the study was to determine whether the time intervals of imaging had any effect on the values of the sacroiliac index. Imaging was performed every 30 min up to 300 min and the indices were calculated at the time intervals mentioned. We found that the values of the sacroiliac index increased in the group of normal subjects until 150 min after the application of the radiopharmaceutical, and that in the group of subjects who had sacroiliitis they increased until 210 min. The results show that the time interval optimal to quantitative sacroiliac joint imaging is at least 3 1/2 h after administration of the radiopharmaceutical.