ObjectivesGonadotropin-releasing hormone (GnRH) stimulates immune responses; therefore, antagonizing GnRH with cetrorelix may have anti-inflammatory effects. The aim of this study was to assess short-term cetrorelix therapy in rheumatoid arthritis (RA) patients.MethodIn this proof-of-concept, randomized, double-blind study involving 99 patients with active, long-standing RA, 48 patients received subcutaneous cetrorelix (5 mg/day on days 1 and 2; 3 mg/day on days 3–5) and 51 received placebo. The primary end-point was the change in the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) by day 5, when the greatest GnRH suppression was anticipated. Secondary end-points included the change in tumour necrosis factor (TNF)-α, and achievement of American College of Rheumatology (ACR) responses and DAS28-CRP < 2.6 by day 5. Patients were followed up on days 10 and 15.ResultsBy day 5, DAS28-CRP was non-significantly reduced by 0.82 in the cetrorelix group compared to a 0.57 reduction in the placebo group (p = 0.091), TNF-α (log pg/mL) was significantly reduced in the cetrorelix group compared with the placebo group [0.55, 95% confidence interval (CI) 0.08–1.01, p = 0.023], and more patients on cetrorelix achieved ACR20 responses (40% vs. 18%, p = 0.015) and DAS28-CRP < 2.6 (13% vs. 0%, p = 0.009). Inflammatory markers increased towards baseline levels after withdrawal of treatment. Rates of adverse events were similar in both groups.ConclusionsAlthough there was no significant difference in the primary end-point between groups, antagonizing GnRH led to significant improvements in key secondary end-points. Thus, GnRH antagonists may have rapid anti-inflammatory effects in RA, already occurring within 5 days. The data suggest a novel mode of action for TNF-α inhibition in RA, and potentially in other autoimmune diseases.
Background Spondylarthritis is a rheumatic disease with axial and peripheral symptoms. It is divided into 6 groups; Ankylosing spondylitis, Psoriatic arthritis, Arthritis associated with inflammatory bowel disease, Reactive arthritis, Unspecified spondyloarthritis and Juvenile spondyloarthritis. There is an ongoing discussion whether it is one disease or separate diseases. The prevalence of spondylarthritis have been reported ranging from 0,3% to 1,9% in different populations. The proportion with concommitant psoriasis varies from 13% to 60%. Psoriatic arthritis, especially with predominantly periphera symptomsl is often seen as a separate entity, and will often not be included in the spondyloarthritis cohorts. We do not know if spondylarthritis with concommitant psoriasis is different from spondylarthritis without psoriasis. Objectives To compare spondylarthritis patients from Rana, Norway with and without psoriasis. Are they different in age, gender, body mass index, inflammation, disease activity, physical function, proportion of synovitis, inflammatory backpain, radiological sacroileitis, sacroileitis on mri, axial disease only, combined peripheral and axial disease, inflammatory bowel disease, acute uveitis, reactive arthritis and HLAB27 positivity? Do the data support that psoriatic arthritis is a separate entity or is it just spondylarthritis with psoriasis? Methods Patients with spondylarthritis, inclusive of psoriatic arthritis were recruited from hospital registers, family doctors and by advertisement in local newspaper. Clinical data, Crp HLAB27 were collected, x-ray and mri of SI-joint was performed if the patient had inflammatory backpain. If they fulfilled the ESSG-critera for Spondylarthritis they were included. The first degree relatives of the included patients were contacted and asked for symptoms of synovitis or inflammatory bacppain by questionnaire. Symptomatic relatives were investigated, and included if they fulfilled the ESSG-critera. 387 spondylarthrits patients were included. 162 patients with psoriasis were compared to 225 patients without psoriasis. 273 patients had mriof SI-joints Statistic testing with SPSS Chi square test or Students T-test Results Spondylarthritis patients with psoriasis are approximately 4 years older, they are more likely to have synovitis, axial disease only and combined peripheral and axial disease. They were less likely to have inflammatory backpain, radiological sacroileitis and HLAB27 positivity. There was no difference in gender,body mass index, inflammatory bowel disease, reactive arthritis, acute uveitis, Crp, disease activity and physical function. They were as likely to have sacroileitis (ASAS-definition) on mri. Conclusions Spondylarthritis with and without concomitant psoriasis have many similarities, but also differences. A possible explanation can be that concommittant psoriasis modifies spondylarthritis. References Haglund E, Bremander AB, Petersson IF, Strömbeck B, Bergman S, Jacobsson LT, Turkiewicz A, Geborek P, Englund M. Prev...
the treatment of refractory RA but experience with TNF-a antagonisers in JIA is limited. Objectives We report the use of Infliximab in 3 patients with systemic JIA and polyarthritis. Methods LS (18 yrs) and JD (11 yrs), girls with systemic-onset JIA at the age of 11 and 3, had persistent, destructive polyarthritis. AP (10 yrs), a boy with systemic-onset JIA at the age of 5 had persistent systemic activity as well as severe polyarthritis. All 3 failed NSAID, corticosteroids, (high-dose) MTX and CsA treatment and suffered from severe growth impairment and osteoporosis. All patients started Infliximab therapy at 3 mg/kg (weeks 0, 2, 6 and then 8-weekly). Active joint number (AJN), limited joint number (LJN), visual analogue scale for global well being (VASg) and pain (VASp), Childhood Health Assessment Questionnaire (CHAQ), serum CRP and serum IL-6 were assessed. Results At present, LS completed 26, JD 38 and AP 86 treatment weeks. LS experienced a manifest decrease in AJN (17 to 1). LJN was unchanged (8). Functional scores decreased markedly: VASg 78 to 10, VASp 45 to 10, CHAQ 1.2 to 0.3. CRP decreased (15 to 3 mg/l) and steroids were tapered from 6 to 3 mg daily. JD showed a similar response: AJN and LJN decreased rapidly (38 to 5 and 41 to 7). VASg, VASp and CHAQ all dropped markedly: 50 to 15, 50 to 10 and 2.1 to 1.4. CRP and ESR decreased (22 to 5 mg/L and 51 to 26 mm/hr). Steroid dose was kept at 4 mg daily. AP experienced a decrease in AJN (9 to 3) and in LJN (12 to 4) during the first 18 weeks. As systemic inflammation persisted, Infliximab dose was increased to 5, later to 10 mg/kg. Whereas AJN and LJN decreased further to 0 and 2, systemic symptoms and the acute phase response persisted: CRP and ESR fluctuated (15-148 mg/l and 45 ? 183 mm/h, respectively). Functional scores varied and reflected the increasing discomfort of preexisting joint damage. Steroid dose was tapered from 12 to 7 mg daily. Infliximab was safe and well tolerated in all 3 patients: possible adverse reactions were fever (AP, once) and upper respiratory tract infection (AP three, JD once). TNF-a blockade with Infliximab in these patients with systemic-onset polyarticular JIA induced a rapid, sustained control of polyarthritis, with concomitant improvement of function, global well being and pain and decrease in biochemical inflammation. Systemic inflammation, however, did not respond to TNF-a blockade. This was evident in patient AP whose articular disease clearly responded but who had a persistent acute phase response with persistently elevated levels of CRP and IL-6. Conclusion Infliximab is promising for the treatment of JIA. The observed dissociation between response of articular and systemic disease indicates that different cytokine networks may operate in systemic and articular inflammation of JIA.
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