Therapy for systemic juvenile rheumatoid arthritis with γ‐interferon: A pilot study of nine patients

Abstract

Nine severely ill patients with a confirmed diagnosis of systemic juvenile rheumatoid arthritis were treated with recombinant y-interferon (y-IFN) in addition to the therapy they were previously receiving for their disease. Improvements in clinical symptoms were noted in 7 of the patients, and median laboratory values also showed a marked improvement after y-IFN treatment. A relapse occurred in 1 patient. The results of this study should stimulate further research on the use of y-IFN in systemic juvenile rheumatoid arthritis, particularly in determining the appropriate effective dosage.Over 800 adults with rheumatoid arthritis (RA) have been treated with y-interferon (yIFN) in Germany since 1983 (Brzoska J: unpublished data). Severe side effects have not been observed. In a recent placebo-controlled double-blind trial, 58% of the RA patients responded to y-IFN (I). However, despite its apparent efficacy, its mode of action is not yet clearly understood (2). The present pilot study of y-IFN was Submitted for publication April 5, 1988; accepted in revised form December 13, 1988. performed with patients with systemic juvenile rheumatoid arthritis (JRA), since this disease often has a high morbidity and mortality rate ( 3 ) despite the current methods of treatment, which include azathioprine, gold, D-penicillamine, and cytotoxic drugs.Patients and methods. Nine severely ill patients with a confirmed diagnosis of systemic JRA according to the criteria of the American Rheumatism Association (4) were selected for study. They had not responded satisfactorily to nonsteroidal antiinflammatory drugs (NSAIDs) and immunosuppressive therapy, and therefore had been given corticosteroids for long-term treatment (Table 1). In addition to their current regimen, the patients were treated with recombinant y-IFN (Biogen, Cambridge, MA, through Bioferon, Laupheim, FRG). The initial dosage during the first 3 weeks was 0.5 pglkg body weight, daily, administered subcutaneously; the same dosage was given for 3 further weeks 3 times a week. Then, depending upon each patient's response to therapy, the dosage was individually reduced by lowering the frequency of injections to either twice or once a week. Clinical parameters, joint function, and laboratory data (hemoglobin level, leukocyte and thrombocyte count, erythrocyte sedimentation rate [ESR], levels of C-reactive protein [CRP] , serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and lactate dehydrogenase, and urinalysis) were assessed before initiating y-IFN treatment and once monthly during therapy.Results. Diverse improvements were observed in 7 of 9 patients who had a history of systemic JRA progressing over several years. These patients' general condition improved during the first weeks of treatment. In 2 boys, intermittent attacks of fever

Juvenile Rheumatoid Arthritis

“…Due to this finding, a placebocontrolled double-blind study with gamma interferon in adults with rheumatoid arthritis was undertaken. 65 The results of the study showed a 58% response to the treatment. Since then, gamma interferon has been studied as a pilot trial in 9 pediatric patients with systemic onset JRA.…”

“…Findings in an adult population with rheumatoid arthritis have shown that gamma interferon is diminished by leukocytes in vitro. 65 Additional research has shown the effectiveness over time with gamma interferon in the treatment of adult RA when dosage decreases are made. Due to this finding, a placebocontrolled double-blind study with gamma interferon in adults with rheumatoid arthritis was undertaken.…”

“…Since then, gamma interferon has been studied as a pilot trial in 9 pediatric patients with systemic onset JRA. 65 The dose given was 0.5 mcglkglday subcutaneously every day for the first three weeks. The next three weeks the dose was the same but was administered 3 times a week.…”

Juvenile Rheumatoid Arthritis

“…IFN-β and IFN-γ down-regulate pro-inflammatory cytokine and up-regulate anti-inflammatory cytokine production and may thus have potential as a therapy for RA. [151,152] Most of the studies were double-blind and placebo-controlled, and were small, each with <50 patients.…”

Cytokines in rheumatic diseases

“…For example, ,y-IFN has already been used with varying success as a therapeutic agent in the treatment of rheumatoid arthritis in both adults and children [62]. In large double-blind clinical trials, results have generally been indeterminate [63].…”