Extended report Ann Rheum Dis 2010;69:503–509. doi:10.1136/ard.2009.119149 503 Beneficial effects of a 3-week course of intramuscular glucocorticoid injections in patients with very early inflammatory polyarthritis: results of the STIVEA trial S M M Verstappen, 1 M J McCoy, 1 C Roberts, 2 N E Dale, 1 A B Hassell, 3 D P M Symmons, 1 the STIVEA investigators ABSTRACT very early inflammatory polyarthritis (IP) with a 3-week course of intramuscular (IM) methylprednisolone acetate may postpone the need for disease-modifying antirheu- matic drugs (DMARDs) and prevent IP from evolving into rheumatoid arthritis (RA). duration) were randomised to receive three injections of either 80 mg IM methylprednisolone acetate or placebo, given at weekly intervals. Assessments were monthly until 6 months after the first injection, and then concluded at 12 months. The primary outcome was the need to start DMARDs by the 6-month assessment. Secondary out- comes included disease activity and final clinical diagnosis by the rheumatologist at 12 months. likely to need DMARDs during the first 6 months of the trial than patients in the glucocorticoid group (61%) (adjusted OR = 2.11, 95% CI 1.16 to 3.85, p = 0.015). Disease activity did not differ between the two groups at 12 months, probably because many patients in the placebo group started DMARDs early in the study. After 12 months, the arthritis had resolved without the need for DMARDs in 9.9% (11/111) of the patients in the placebo group and in 19.8% (22/111) in the glucocorticoid-treated group (adjusted OR = 0.42, 95% CI 0.18 to 0.99, p = 0.048). IM methylprednisolone acetate appears to postpone the prescription of DMARDs and prevent one in 10 patients from progressing into RA. The body normally responds either locally or systemically to an inflammatory stimulus by producing proinflammatory cytokines. Systemically, the release of proinflammatory cyto- kines results in stimulation of the hypothalamic- pituitary-adrenal axis and release of corticosteroids. This should then curtail the inflammation. Inflammatory polyarthritis (IP) is an example of a systemic inflammatory stimulus, but not all people who develop IP go into remission. Evidence from the Norfolk Arthritis Register suggests that at least half of those who develop IP lasting at least 4 weeks go on to develop chronic rheumatoid arthritis (RA). 1 One possible explanation for the persistence of IP may be a defect in the patient’s systemic anti-inflammatory response. Reduced corticosteroid or ACTH levels have been found in patients with RA, whereas one would expect elevated levels due to inflammation. 2–4 Oral glucocorticoids are commonly prescribed to patients with RA because of their clinical efficacy. 5–7 However, only a few randomised controlled trials have examined the effect of intramuscular (IM) administration of glucocorticoids in patients with inflammatory arthritis. In three randomised con- trolled trials, IM glucocorticoids were given at the same time as starting disease-modifying antirheu- matic drugs (DMARDs). 8–10 In one study no appar- ent benefit was shown from the glucocorticoid injections. 10 In two other studies, IM glucocorticoid injections had a significant short-term benefit when compared with either oral glucocorticoids or pla- cebo. 89 These results were confirmed in another study, comparing monthly IM glucocorticoid injec- tions with placebo in patients with established RA, in which a significant reduction in disease activity up to 6 months was found. 11 In the latter study, however, the number of reported adverse events outweighed the observed clinical benefit. Although these studies show that the use of IM glucocorticoids is in general very beneficial, disease duration in these studies was more than 3 months and most patients had already developed RA. In recent years it has become clear that the ‘‘window of opportunity’’ to fundamentally alter the course of RA is very narrow and that treatment should start as early as possible after symptom onset. 12–14 A previously published non-randomised study, exploring the effect of a single dose of glucocorticoids in patients with very early arthritis, showed that patients who went into remission had a median symptom duration of 10 weeks com- pared with a median duration of 20 weeks in those whose arthritis persisted. 15 Thus we hypothesised that administration of IM glucocorticoid injections in very early IP may lead to resolution in an important proportion of cases. PATIENTS AND METHODS Study design and patients This randomised, double-blind, placebo-controlled, multicentre trial examined the effect of IM glucocorticoids in patients with very early IP. General practitioners in the region of 23 participat- ing hospitals were asked to refer patients aged 18 or older who had IP with symptom duration of 4–10 weeks to the rheumatology outpatient clinic. Patients had to have tenderness and soft tissue Objective To evaluate whether treating patients with Methods Patients with very early IP (4–10 weeks’ Results Patients in the placebo group (76%) were more Conclusion Treatment of patients with very early IP with 1 arc Epidemiology Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK 2 Department of Biostatistics, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK 3 arc National Primary Care Centre, Keele University, Keele, Staffs, UK and Department of Rheumatology, Haywood Hospital, Stoke-on-Trent, UK Correspondence to Professor D P M Symmons, arc Epidemiology Unit, Stopford Building, The University of Manchester, Manchester M13 9PT, UK; deborah.symmons@ manchester.ac.uk Accepted 17 September 2009 Published Online First 8 November 2009 on May 22, 2020 by guest. 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