Kalevi Koota

Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial

BACKGROUND The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.

Cardiovascular Mortality in Patients with Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA), 500 men and 500 women, aged 40 years and over, together with a control population matched by age and sex were followed up with respect to cause-specific mortality over a 10-year period. The overall mortality was significantly higher in both men and women with RA than in the controls. A statistically significant increase in mortality from all cardiovascular diseases (p less than 0.001) and cardiac diseases (p = 0.004) was observed in men with RA but not in women with RA compared to corresponding controls. No difference in mortality from cerebrovascular diseases was observed between RA patients and controls.

DEATH RATE AND CAUSES OF DEATH IN PATIENTS WITH RHEUMATOID ARTHRITIS

Patients with rheumatoid arthritis, 500 males and 500 females, aged 40 years or over, and an age- and sex-matched control population were observed over a 3-year period. During the follow-up, 122 RA patients and 69 controls had died. The most common causes of death in RA patients were cardiovascular diseases (57 patients), renal failure (27 patients), infections (19 patients), and malignant neoplasms (11 patients); in the controls, the respective data are: cardiovascular diseases (35 people), malignant neoplasms (21 people), accidents (7 people), and infections (5 people).

Death rate and causes of death in RA patients during a period of five years.

Patients with rheumatoid arthritis, 500 males and 500 females, aged 40 years or over, together with an age and sex matched control population, were observed over a 5-year period. During the follow-up 176 RA patients and 107 controls died. The most common causes of death in RA patients were cardiovascular diseases (86 patients), renal failure (33 patients), infections (23 patients), and malignant neoplasms (21 patients); in the controls, the corresponding data are cardiovascular diseases (53), malignant neoplasms (30), infections (9), and accidents (8).

Causes of Death in Autopsied Ra Patients

Among 3115 autopsied patients, rheumatoid arthritis was registered in 41 patients (1.3%). The causes of death of these were correlated with the causes of death of 310 non-rheumatoid autopsied patients. Of the RA patients, 32% died from cardiovascular disease, 24% from infection, 27% from renal failure and 7% from malignant disease. Of the control patients, 42% died from cardiovascular disease, 9% from infection, 3% from renal failure, and 23% from malignant disease. The low frequency of malignant disease as a cause of death in RA patients may be due to a continuous immunological stimulation or due to a missed diagnosis of RA in patients who died from malignant disease.

Osmic Acid in Rheumatoid Synovitis: A Controlled Study

Ninety-nine adult RA patients with knee joint synovitis were randomized into two groups. The knee joints of the first group (52 patients) were treated with osmic acid and those of the second group (47 patients) with a placebo. After 6 months, the incidence of hydrops and pain was statistically less significant in joints treated with osmic acid. the result was better in joints without advanced radiological destruction. It is concluded that osmic acid is still of benefit in the local treatment of rheumatoid knee joint synovitis at an early stage.

Death Certificate and Mortality in Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA), 500 males and 500 females, aged 40 years and over, together with an age- and sex-matched control population, were observed over a 10-year period. Altogether 208 male and 148 female RA patients died during the follow-up period. RA was mentioned on the death certificates of 111 men (53%) and for 96 women (65%). Serious underreporting of RA was observed when the main cause of death was malignant neoplasms and diseases of the circulatory system. The results show that analysis of the causes of death can be highly biased if the RA diagnosis is based only on information on the death certificate.