Rheumatoid Arthritis: Bruyn GA

Bruyn GA, Schmidt WA. · Department of Rheumatology, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands. · Best Pract Res Clin Rheumatol. · Pubmed #19393570 No free full text.

Abstract: Among the most important reasons for the increased use of ultrasound by rheumatologists is its feasibility to guide injections. Correct positioning of the needle in the targeted structure occurs much more frequently with ultrasound guidance than with conventional positioning without imaging. The sonographer can mark the skin above the structure, using ultrasound to localize this point and to estimate the depth of the structure. Alternatively, the sonographer might introduce the needle under direct sonographic visualisation, holding the probe in one hand and the needle in the other. The needle can be longitudinally parallel to the probe, with an angle of about 45 degrees to the probe. It can be introduced close to the middle of the probe or opposite the probe; the needle can be also depicted transversely. Ultrasound allows needle guidance in nearly all important structures of shoulders, elbows, hand, hips, knees and feet. Education involves training to coordinate probe and needle in sponges, chicken, cheese and other objects. Knowledge of anatomy, probe positioning and the ability to coordinate probe and needle are necessary when injecting patients with sonographic guidance. The rheumatologist might start with easy approaches in which the needle is parallel to the probe.

Joshua F, Lassere M, Bruyn GA, Szkudlarek M, Naredo E, Schmidt WA, Balint P, Filippucci E, Backhaus M, Iagnocco A, Scheel AK, Kane D, Grassi W, Conaghan PG, Wakefield RJ, D'Agostino MA. · Department of Rheumatology, St. George Hospital, University of NSW, Sydney, Australia. · J Rheumatol. · Pubmed #17407235 No free full text.

Abstract: This report presents the results of a recent systematic review performed by the OMERACT Ultrasound Group on the metric properties of ultrasound for the detection of synovitis in inflammatory arthritis. Reviews were conducted for the hand, wrist, elbow, shoulder, knee, ankle, and foot; most reports were related to the hand and knee, and the most common disease process was rheumatoid arthritis. The review highlights the current gaps in the literature, including a lack of reliability data with respect to intra-occasion and intra- and inter-reader reliability. Current work by our group is addressing these issues.

Kalksma R, Jansen TL, Bruyn GA. · Leeuwarden Medical Centre, Department of Rheumatology, The Netherlands. · Neth J Med. · Pubmed #12430576 links to  free full text

Abstract: Rheumatoid arthritis is a chronic inflammatory disease that primarily affects the joints and is often treated with non-steroidal anti-inflammatory drugs (NSAIDs) on demand and disease-modifying antirheumatic drugs (DMARDs), with a relatively low risk of side effects. Although an infrequent side effect, neutropenia has been described as a sequel of NSAIDs. We report a case of neutropenia proven (by rechallenge) to be due to naproxen therapy. The literature on neutropenia during treatment with NSAIDs and DMARDs is briefly reviewed.

Gerards AH, Landewé RB, Prins AP, Bruyn GA, Goei Thé HS, Laan RF, Dijkmans BA, Bruijn GA. · VU Medical Centre and Jan van Breemen Instituut, Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #12634224 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy and toxicity of cyclosporin A (CsA) monotherapy with CsA plus methotrexate (MTX) combination therapy in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS: 120 patients with active RA, rheumatoid factor positive and/or erosive, were randomly allocated to receive CsA with MTX (n=60) or CsA with placebo (n=60). Treatment with CsA was started in all patients at 2.5 mg/kg/day and increased to a maximum of 5 mg/kg/day in 16 weeks. MTX was started at 7.5 mg/week and increased to a maximal dose of 15 mg/week at week 16. Primary outcomes were clinical remission (Pinals criteria) and radiological damage (Larsen score), at week 48. RESULTS: Treatment was discontinued prematurely in 27 patients in the monotherapy group (21 because of inefficacy, and six because of toxicity) and in 26 patients in the combination therapy group (14 and 12, respectively). At week 48, clinical remission was achieved in four patients in the monotherapy group and in six patients in the combination therapy group (p=0.5). The median Larsen score increased to 10 (25th, 75th centiles: 3.5; 13.3) points in the monotherapy group and to 4 (1.0; 10.5) points in the combination therapy group (p=0.004). 28/60 (47%) of patients in the monotherapy group v 34/60 (57%) of patients in the combination therapy group had reached an American college of Rheumatology 20% (ACR20) response (p=0.36) at week 48; 15/60 (25%) v 29/60 (48%) of patients had reached an ACR50 response (p=0.013); and 7 (12%) v 12 (20%) of patients had reached an ACR70 response (p=0.11).Their was a tendency towards more toxicity in the combination therapy group. CONCLUSIONS: In patients with early RA, neither CsA plus MTX combination therapy nor CsA monotherapy is very effective in inducing clinical remission. Combination therapy is probably better at improving clinical disease activity, and definitely better at slowing radiological progression. Combination therapy should still be compared with methotrexate monotherapy.

de Nijs RN, Jacobs JW, Bijlsma JW, Lems WF, Laan RF, Houben HH, ter Borg EJ, Huisman AM, Bruyn GA, van Oijen PL, Westgeest AA, Algra A, Hofman DM, Anonymous00207. · Department of Rheumatology and Clinical Immunology, F02.127, University Medical Center, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #11752508 links to  free full text

Abstract: OBJECTIVE: This study was designed to determine whether the prevalence of vertebral deformities in patients with rheumatoid arthritis (RA) treated with corticosteroids (Cs) is higher than in RA patients not receiving Cs therapy. PATIENTS AND METHODS: This multicentre cross-sectional study included 205 patients with RA who were receiving Cs orally on a daily basis and 205 patients with RA who did not receive Cs, matched for sex and age. Vertebral deformities were scored according to the Kleerekoper method. RESULTS: Vertebral deformities were found in 52 (25%) patients on Cs and in 26 (13%) patients not on Cs. Sixteen (8%) patients in the group on Cs had experienced clinical manifestations of an acute vertebral fracture in the past vs only three patients (1.5%) among those not on Cs. The use of Cs tended to increase the risk of developing a vertebral deformity [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81-2.99] and symptomatic vertebral fracture (adjusted OR 1.42, 95% CI 0.24-8.32). Each 1-mg increase in the current daily Cs dose increased the risk of a vertebral deformity (adjusted OR 1.05, 95% CI 0.98-1.13) and of a symptomatic vertebral fracture (adjusted OR 1.05, 95% CI 0.89-1.24). CONCLUSION: There is a higher prevalence of vertebral deformities and clinical manifestations of vertebral fractures in patients on Cs than in those not on Cs. Our data indicate that the use of Cs and each 1-mg increase in the current daily Cs dose may increase the risk of development of a vertebral deformity and symptomatic vertebral fracture in patients with RA.

Bruyn GA, Griep EN, Korff KJ. · No affiliation provided · Lancet. · Pubmed #10359439 No free full text.

This publication has no abstract.

Bruyn GA, Naredo E, Möller I, Moragues C, Garrido J, de Bock GH, d'Agostino MA, Filippucci E, Iagnocco A, Backhaus M, Swen WA, Balint P, Pineda C, Milutinovic S, Kane D, Kaeley G, Narvaez FJ, Wakefield RJ, Narvaez JA, de Augustin J, Schmidt WA. · Department of Rheumatology, Medisch Centrum Leeuwarden, 8934 AD Leeuwarden, Leeuwarden, The Netherlands. · Ann Rheum Dis. · Pubmed #18390570 No free full text.

Abstract: OBJECTIVE: To assess the intra and interobserver reproducibility of musculoskeletal ultrasonography (US) among rheumatologists in detecting destructive and inflammatory shoulder abnormalities in patients with rheumatoid arthritis (RA) and to determine the overall agreement between US and MRI. METHODS: A total of 14 observers examined 5 patients in 2 rounds independently and blindly of each other. US results were compared with MRI. Overall agreement of all findings, of positive findings on MRI, as well as intra and interobserver reliabilities, were calculated. RESULTS: Overall agreement between US and MRI was seen in 79% with regard to humeral head erosions (HHE), in 64% with regard to posterior recess synovitis (PRS), in 31% with regard to axillary recess synovitis (ARS), in 64% with regard to bursitis, in 50% with regard to biceps tenosynovitis (BT), and in 84% for complete cuff tear (CCT). Intraobserver and interobserver kappa was 0.69 and 0.43 for HHE, 0.29 and 0.49 for PRS, 0.57 and 1.00 for ARS, -0.17 and 0.51 for bursitis, 0.17 and 0.46 for BT and 0.52 and 0.6 for CCT, respectively. The intraobserver and interobserver kappa for power Doppler (PD) was 0.90 and 0.70 for glenohumeral signals and 0.60 and 0.51 for bursal signals, respectively. CONCLUSIONS: US is a reliable imaging technique for most shoulder pathology in RA especially with regard to PD. Standardisation of scanning technique and definitions of particular lesions may further enhance the reliability of US investigation of the shoulder.

van der Heijde D, Klareskog L, Landewé R, Bruyn GA, Cantagrel A, Durez P, Herrero-Beaumont G, Molad Y, Codreanu C, Valentini G, Zahora R, Pedersen R, MacPeek D, Wajdula J, Fatenejad S. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Arthritis Rheum. · Pubmed #18050208 links to  free full text

Abstract: OBJECTIVE: The Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) is a 3-year, double-blind, multicenter study evaluating the efficacy and safety of etanercept, methotrexate, and the combination of etanercept plus methotrexate in patients with active rheumatoid arthritis (RA). The results after 1 and 2 years of the study have been previously reported. Here we provide the 3-year clinical and radiographic outcomes and safety of etanercept, methotrexate, and the combination in patients with RA. METHODS: In this randomized, double-blind, multicenter TEMPO study, 682 patients received etanercept 25 mg twice weekly, methotrexate < or =20 mg weekly, or the combination. Key efficacy assessments included the Disease Activity Score (DAS) and the DAS in 28 joints. RESULTS: Combination therapy resulted in significantly greater improvement in the DAS and in more patients with disease in remission than either monotherapy. This finding was confirmed by longitudinal analysis; patients receiving combination therapy were more than twice as likely to have disease in remission than those receiving either monotherapy. Independent predictors of remission included male sex, lower disease activity, lower level of joint destruction, and/or better physical function. Combination and etanercept therapy both resulted in significantly less radiographic progression than did methotrexate (P < 0.05). Etanercept and combination treatment were well tolerated, with no new safety findings. CONCLUSION: Etanercept plus methotrexate showed sustained efficacy through 3 years and remained more effective than either monotherapy, even after adjustment for patient withdrawal. Combination therapy for 3 years led to disease remission and inhibition of radiographic progression, 2 key goals for treatment of patients with RA.

Bruyn GA, Tate G, Caeiro F, Maldonado-Cocco J, Westhovens R, Tannenbaum H, Bell M, Forre O, Bjorneboe O, Tak PP, Abeywickrama KH, Bernhardt P, van Riel PL, Anonymous00077. · Medisch Centrum Leeuwarden (Zuid), Afd. Reumatologie, Leeuwarden, 8934 AD, The Netherlands. · Ann Rheum Dis. · Pubmed #18037627 No free full text.

Abstract: OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.

Wakefield RJ, D'Agostino MA, Iagnocco A, Filippucci E, Backhaus M, Scheel AK, Joshua F, Naredo E, Schmidt WA, Grassi W, Moller I, Pineda C, Klauser A, Szkudlarek M, Terslev L, Balint P, Bruyn GA, Swen WA, Jousse-Joulin S, Kane D, Koski JM, O'Connor P, Milutinovic S, Conaghan PG, Anonymous00480. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #17407236 No free full text.

Abstract: Ultrasound (US) is a relatively new imaging modality in rheumatology that offers great potential as a diagnostic and management tool. In 2004, an OMERACT Ultrasound Special Interest Group was formed to address the metric qualities of US as a potential outcome measure. A preliminary systematic review highlighted the deficiencies in the literature, particularly with regard to the reliability of interpreting and acquiring images; as a consequence, a number of exercises were proposed to address these issues. This report describes a series of iterative studies that have resulted in improved intra- and inter-reader reliability for detecting and scoring synovitis from both static and real-time images of the hand joints of patients with rheumatoid arthritis. The reliability of acquiring images was also enhanced using standardized positions. Future studies will assess the value of US in clinical trials.

Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D'Agostino MA, Sanchez EN, Iagnocco A, Schmidt WA, Bruyn GA, Bruyn G, Kane D, O'Connor PJ, Manger B, Joshua F, Koski J, Grassi W, Lassere MN, Swen N, Kainberger F, Klauser A, Ostergaard M, Brown AK, Machold KP, Conaghan PG, Anonymous00384. · Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK. · J Rheumatol. · Pubmed #16331793 No free full text.

Abstract: Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis.

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.

Van Roon EN, Jansen TL, Mourad L, Houtman PM, Bruyn GA, Griep EN, Wilffert B, Tobi H, Brouwers JR. · Department of Hospital Pharmacy and Clinical Pharmacology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands. · Br J Clin Pharmacol. · Pubmed #15255803 links to  free full text

Abstract: AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.

Van Roon EN, Jansen TL, Mourad L, Houtman PM, Bruyn GA, Griep EN, Wilffert B, Tobi H, Brouwers JR. · Department of Hospital Pharmacy and Clinical Pharmacology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands. · Br J Clin Pharmacol. · Pubmed #15151525 links to  free full text

Abstract: AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, from outpatient medical records a standard dataset was collected including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient-years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual, rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within a year after start of leflunomide treatment, mainly because of adverse drug reactions.

Bruyn GA, Iagnocco A, Naredo E, Wakefield RJ, Schmidt WA. · No affiliation provided · Arthritis Rheum. · Pubmed #15457483 links to  free full text

This publication has no abstract.

Bruyn GA. · No affiliation provided · J Rheumatol. · Pubmed #15229972 links to  free full text

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Jansen TL, Bruyn GA. · No affiliation provided · J Rheumatol. · Pubmed #15124273 links to  free full text

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Bruyn GA, Veenstra RP, Halma C, Grond J. · No affiliation provided · Arthritis Rheum. · Pubmed #12687568 links to  free full text

This publication has no abstract.