Rheumatoid Arthritis: Jahangier ZN

van der Zant FM, Boer RO, Moolenburgh JD, Jahangier ZN, Bijlsma JW, Jacobs JW. · Department of Nuclear Medicine, Hospital Medical Center Alkmaar, The Netherlands. · Clin Exp Rheumatol. · Pubmed #19327243 No free full text.

Abstract: OBJECTIVE: To perform a systemic review and meta-analysis on the effectiveness of radiosynoviorthesis (RSO). METHODS: A search of medical databases was conducted. Criteria for inclusion: articles in English, minimum follow-up of 6 months, specification of joint disease, reported outcome of at least 5 RSOs. The studies were scored for quality by the Oxford Centre of Evidenced-based Medicine Levels of Evidence, from 1 to 4. RESULTS: Twenty-one (21) studies were included (3 quality 1b, 5 2b and 13 4), analysing 169Erbium/186Rhenium-RSO used predominantly in small joints and 49 (1 quality 1b, 10 2b and 38 4) on 90Yttrium-RSO used predominantly in knee joints. The reported success rates of 169Erbium/186Rhenium-RSO ranged from 69-100% at 6 months, and from 54-100% at > or =12 months; for 90Yttrium they were 24-100% and 29-94%, res-pectively. Studies comparing the effect of RSO with that of glucocorticoid (GC) or saline injection alone were pooled. At 6 months, the pooled odds ratio favouring RSO of the knee with Yttrium over control is 4 (confidence interval (CI) 95% 1.2-14), p=0.02, but at 12 months the ratio was 1.7 (CI95% 0.69-4), p=0.26. For RSO of small joints with Erbium/Rhenium compared to controls, the pooled odds ratio at 6 months is 2 (CI95% 0.66-6), p=0.22 and at 12 months 2 (CI95% 1.09-3.5), p=0.03. CONCLUSION: Reported success rates of RSO are high, but differences in effect with GC injection are less evident, although there is marked heterogeneity in study design of the (small number of) comparative studies.

van Jaarsveld CH, Jahangier ZN, Jacobs JW, Blaauw AA, van Albada-Kuipers GA, ter Borg EJ, Brus HL, Schenk Y, van Der Veen MJ, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center, PO Box 85500, 3508 GA Utrecht, the Netherlands. · Rheumatology (Oxford). · Pubmed #11136881 links to  free full text

Abstract: OBJECTIVE: To evaluate the toxicity of slow-acting anti-rheumatic drugs (SAARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) in early rheumatoid arthritis. METHODS: Patients were randomized to receive a SAARD-hydroxychloroquine (HCQ; n=120), i.m. gold (n=114) or methotrexate (MTX; n=118)-or a NSAID only (n=67). Patients in the three SAARD groups were allowed to take NSAIDs. Follow-up included 545 patient-years (p-yr). Adverse effects were attributed to specific medications using the Naranjo scoring method. RESULTS: Fifty-five per cent of the patients suffered from adverse effect(s). Adverse effects were most common during i.m. gold therapy (87 per 100 p-yr), which led to permanent discontinuation of this treatment in 31 cases. The incidences of adverse effects that were probably attributable to NSAIDs in patients treated simultaneously with a SAARD were similar for the three SAARD groups. The mean period until the first adverse effect was longer in the MTX group (39 weeks) than in the HCQ group (27 weeks). Baseline clinical and sociodemographic parameters were not predictive of the occurrence of adverse effects. CONCLUSION: No adverse effect could be classified as definitely related to either SAARDs or NSAIDs by the Naranjo scoring method. The incidence of possible adverse effects of NSAIDs and SAARDs was 72 per 100 p-yr, and adverse effects led to permanent discontinuation of the therapy in 56 cases (13%) (31 patients receiving i.m. gold, 12 receiving MTX, 10 receiving HCQ and three receiving NSAID only).

Jahangier ZN, Jacobs JW, Kraan MC, Wenting MJ, Smeets TJ, Bijlsma JW, Lafeber FP, Tak PP. · Department of Rheumatology & Clinical Immunology, F02.127, University Medical Center Utrecht, Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #16627543 No free full text.

Abstract: OBJECTIVE: To explore whether pretreatment features of synovial tissue in patients with gonarthritis could predict the clinical effect of radiation synovectomy with yttrium-90 (90Y) and glucocorticoids or with intra-articular glucocorticoids alone. METHODS: A synovial biopsy was carried out blindly 2 weeks before treatment in 66 patients with persistent gonarthritis, who were randomised to treatment either with 90Y and triamcinolone or with placebo and triamcinolone. Immunohistochemistry was used to detect T cells, macrophages, B cells, plasma cells, fibroblast-like synoviocytes, adhesion molecules and pro-inflammatory cytokines. Stained sections were evaluated by digital image analysis. Individual patient improvement was expressed using a composite change index (CCI; range 0-12). Successful treatment was defined as CCI > or = 6 after 6 months. RESULTS: Patients with rheumatoid arthritis, psoriatic arthritis, undifferentiated arthritis and other causes of gonarthritis were included. The overall response rate was 47%. Clinical efficacy in both therapeutic groups was similar and not dependent on diagnosis. No significant differences were noted between baseline microscopic features of synovial tissue inflammation in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis (ie, all diagnoses other than rheumatoid arthritis). The number of macrophages in the synovial sublining was significantly higher in responders than in non-responders (p = 0.002), independent of treatment group and diagnosis. The clinical effect was positively correlated with pretreatment total macrophage numbers (r = 0.28; p = 0.03), sublining macrophage numbers (r = 0.34; p = 0.005) and vascular cell adhesion molecule 1 expression (r = 0.25; p = 0.04). CONCLUSION: The observations support the view that intra-articular treatment either with 90Y and glucocorticoids or with glucocorticoids alone is especially successful in patients with marked synovial inflammation.

Jahangier ZN, Jacobs JW, Lafeber FP, Moolenburgh JD, Swen WA, Bruyn GA, Griep EN, ter Borg EJ, Bijlsma JW. · Dept. of Rheumatology and Clinical Immunology F02.127, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Arthritis Rheum. · Pubmed #16255016 links to  free full text

Abstract: OBJECTIVE: To compare the clinical efficacy and safety of radiation synovectomy (RSO) with intraarticular (IA) yttrium-90 plus glucocorticoids (GCs) with the efficacy and safety of IA placebo yttrium plus GCs and to identify parameters that predict efficacy. METHODS: The knees of 97 patients with persistent arthritis despite outpatient treatment with IA GCs (n = 113 knees), were treated with either IA (90)Y plus GCs (50%) or IA placebo yttrium plus GCs (50%), followed by 3 days of bed rest in the hospital clinic, with splinting of the treated knee. Predominant diagnoses were undifferentiated arthritis (39%) and rheumatoid arthritis (32%). The clinical effect of therapy was assessed at 6 months using a composite change index (CCI; range 0-12). The primary outcome measure was the response rate (i.e., the percentage of joints with a CCI > or =6). Knees with persistent arthritis after 6 months underwent crossover therapy (51% of the (90)Y plus GCs group versus 45% of the placebo plus GCs group). Adverse effects and radiologic damage during followup were documented. RESULTS: Neither the response rate (48% in both groups), the mean CCI, nor the duration of remission was significantly different between groups. No clinically relevant short-term adverse effects were observed, except for progression of radiologic damage in 34% of the (90)Y plus GCs group versus 28% of the placebo plus GCs group (knee prosthesis placement in 8% versus 1%). The functional and radiologic status at study entry predicted the clinical effect. CONCLUSION: Treatment with (90)Y plus GCs with bed rest and splinting is not superior to IA GCs with bed rest and splinting. Over the short term, both treatments appeared to be safe, although a negative effect of (90)Y on cartilage and bone cannot be ruled out. Thus, it appears that RSO with (90)Y should no longer be considered the treatment of first choice for persistent arthritis of the knee.