This newsletter is produced by Remedica Medical Education and Publishing and is not an official publication of the ACR. Rheumatology.

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1 This newsletter is produced by Remedica Medical Education and Publishing and is not an official publication of the ACR Rheumatology JANUARY 2008 highlights Introduction Edited by Christopher Ritchlin, MD Director, Clinical Immunology Research Center, University of Rochester, NY, USA Contents Continuing Medical Education Information can be found overleaf. Introduction 1 Ankylosing Spondylitis 1 Rheumatoid Arthritis 3 Psoriatic Arthritis 5 Juvenile Arthritis 5 Fracture 6 NSAIDs 7 Systemic Lupus Erythematosus 7 The 2007 annual meeting of the ACR/ARHP was held in Boston, MA, on 6 11 November 2007 combining the 71st ACR and 42nd ARHP annual conferences. Attendance at this ever-growing meeting once again surpassed the previous year s figures, with around delegates from almost 100 countries presenting over 2000 abstracts covering a broad range of basic to clinical science topics. An extensive range of subjects were covered at the meeting, and in Rheumatology Highlights I have chosen a selection of the most important and exciting abstracts relating to current and near-future therapies that are likely to have a direct impact on your daily clinical practice. In particular, we once again highlight data showing that, with the expanding therapeutic armamentarium now available to us, remission is a realistic target in the treatment of rheumatic arthritis. Many of these therapies are also proving invaluable in the treatment of other rheumatic conditions, such as ankylosing spondylitis and psoriatic arthritis, and this issue also features abstracts that concern these and other diseases. We trust that this newsletter will provide you with an interesting, concise, and highly relevant review of the meeting and welcome your feedback and suggestions. Ankylosing Spondylitis Adalimumab reduces uveitis flares in AS RHAPSODY study shows adalimumab is effective for uveitis flares in AS Approximately 20 40% of patients with AS experience at least one episode of anterior uveitis. Previous clinical trials have shown that therapy with either infliximab or etanercept reduced the rate of uveitis flares in AS patients. Data presented at the ACR meeting from the RHAPSODY (Review of Safety and Effectiveness with Adalimumab in Patients with Active Ankylosing Spondylitis) trial, a prospective, multinational, open-label trial designed to examine the effectiveness of adalimumab in the treatment of active AS (n=1250), showed that adalimumab reduced the Jointly sponsored by the University of Kentucky Colleges of Pharmacy and Medicine and Remedica. The University of Kentucky is an equal opportunity university. This newsletter is supported by an educational grant from Abbott

2 incidence of uveitis flares in AS. The AS cohort included 274 patients with uveitis. In RHAPSODY, adult patients with active AS who had an insufficient response to prior NSAID therapy, received open-label adalimumab 40 mg subcutaneously every other week for 12 weeks. Patients with symptomatic uveitis at baseline and/or in the previous year received the same regimen for a total of 20 weeks. Treatment effect was measured at weeks 2, 6, 12, and 20. Diagnosis of uveitis was confirmed by an ophthalmologist. The rate of uveitis flares was reduced by approximately half during treatment with adalimumab compared with the rate prior to the trial (15 flares/ 100 patient years [100-PY] to 7.4 flares/ 100-PY in the entire trial population, 68.4 flares/100-py to 28.9 flares/100-py in the subset with a history of uveitis). Lead investigator of the study Martin Rudwaleit (Charité University Hospital, Germany) said the results pointed to the need for research to better understand uveitis in AS patients. Table 1. Primary endpoints in a trial of infliximab for early inflammatory back pain. All patients Infliximab Placebo p value (baseline) (change from (change from baseline) baseline) Total MRI score ( 6.25 to 0) 0 ( 2 to 1.5) of SI joints, mean (95% CI) New SI lesions 1 (1.2) 11 (12) on MRI, n (%) CI: confidence interval; MRI: magnetic resonance imaging; SI: sacroiliac. Table 2. Secondary endpoints in a trial of infliximab for early inflammatory back pain. All patients Infliximab Placebo p value HAQ, median (IQR) ( ) ( 0.93 to 0.13) (0.38 to 0.00) ASQoL, median (IQR) ( ) ( 10.0 to 2.25) ( 4.50 to 0.75) BASFI, mean (SD) 4.26 (1.71) 2.70 (2.36) 0.47 (2.25) BASDAI, mean (SD) 5.81 (1.46) 3.41 (2.53) 0.75 (2/42) BASDAI50, n (%) 12 (60) 3 (15) ASAS20, n (%) 12 (77.8) 5 (31.3) AS: ankylosing spondylitis; ASAS20: Assessment in AS International Working Group 20% improvement; ASQoL: AS quality of life; BASDAI50: Bath AS Disease Activity Index 50% improvement; BASFI: Bath AS Functional Index; HAQ: health assessment questionnaire; IQR: interquartile range; SD: standard deviation. Table 3. Patients with new onset uveitis Sex Female Female Female Female Male Age AS duration (years) HLA-B27 status Positive Positive Negative Positive Negative Associated Yes Yes Yes Yes No peripheral disease Concomitant DMARDs MTX 15 mg weekly MTX 15 mg weekly Nil Nil MTX 15 mg weekly IBD/psoriasis No No No No No Anti-TNF drug used Etanercept Infliximab Etanercept Etanercept Etanercept Duration of anti-tnf 2 months 20 months 5 months 36 months 2 months before uveitis onset Unilateral/bilateral Bilateral Bilateral Bilateral Bilateral Bilateral Outcome Stopped drug. Infliximab frequency Switched to Continues on Continued etanercept Severe uveitis decreased with no infliximab with good etanercept with for a year with flare with benefit, then stopped response and no as-required topical as-required topical re-challenge further uveitis uveitis treatment uveitis treatment AS: ankylosing spondylitis; DMARD: disease-modifying antirheumatic drug; HLA: human leukocyte antigen; IBD: inflammatory bowel disease; MTX: methotrexate; TNF: tumor necrosis factor. 2 JAN 2008 Rheumatology Highlights

3 Infliximab in early ankylosing spondylitis Infliximab is effective for early inflammatory back pain A study of 40 patients with human leukocyte antigen B27 (HLA-B27)-positive early inflammatory back pain and bone edema demonstrated that treatment with the anti-tumor necrosis factor-α (TNF-α) agent infliximab may be an effective therapy. Patients were randomized to receive infusions of infliximab 5 mg/kg at 0, 2, 6, and 12 weeks or placebo. Concomitant non-steroidal anti-inflammatory drugs (NSAIDs) were permitted for the duration of the study (90% of patients received NSAIDs). The mean age of patients was 28.8 years and mean symptom duration was 15.3 months. The primary endpoint was change in MRI score from baseline to week 16 and a number of secondary endpoints were also assessed (Table 1). Clinical assessments were included as secondary endpoints (Table 2). Paul Emery s group from the University of Leeds, UK, concluded that the significant improvements observed in MRI and clinical endpoints in the infliximab group warrant further research to establish whether the effect of infliximab on bone edema in early ankylosing spondylitis (AS) would inhibit ankylosis. New onset uveitis in AS patients treated with anti-tnf therapy Case reports of new onset uveitis with infliximab and etanercept Investigators from the University of Leeds, UK, reported five cases of new onset uveitis (four treated with etanercept and one with infliximab) out of over 120 AS patients treated at their institution. Patient details are summarized in Table 3. The Leeds team said that, while anti-tnf drugs offer a new treatment option for refractory uveitis, it is clear that their mechanism of action in the eye is not fully understood and may relate to a unique immunological environment in the uvea. Further research is needed to understand the scientific basis for this paradoxical relationship and to identify any factors that may predict a negative outcome. Rheumatoid Arthritis Methotrexate and etanercept in early RA COMET trial results support combination therapy in early RA First results from the COMET (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis) trial were reported by Paul Emery (University of Leeds, UK) in a late-breaking session. COMET is the first major rheumatoid arthritis (RA) clinical trial to use remission as a primary endpoint, and to compare the efficacy and safety of etanercept plus methotrexate (MTX) with MTX alone in patients with active early RA. The double-blind, randomized study was designed with two 12-month periods, and results from Period 1 were presented. The subjects had RA for less than 2 years, had active disease (28-point disease activity score [DAS28] 3.2), mean age 51 years, elevation of erythrocyte sedimentation rate (ESR; 28 mm/h) or C-reactive protein (CRP; 20 mg/l) and were MTX-naive. Of 542 patients enrolled, 274 were randomized to etanercept + MTX and 268 to MTX alone. The primary endpoint was DAS28 remission (<2.6) at week 52. Secondary endpoints included the proportion of patients achieving ACR20, ACR50, and ACR70 at week 52. At week 52, 50% of patients in the combination therapy arm achieved remission versus 28% on MTX alone (p<0.001). Low disease activity (DAS28 3.2) was achieved by 64% and 41% of patients in combination and single therapy arms, respectively (p<0.001). The proportion of patients who achieved DAS28 remission and low disease activity was significantly greater in the etanercept + MTX group by week 2 and at all time points thereafter. ACR responses are shown in Table 4. Serious adverse events (AEs) were reported by 33 (12%) of the patients in the combination therapy arm and by 34 (12.7%) of the patients in the monotherapy arm. There were no differences in rates of serious infections or malignancies and no cases of TB or demyelinating disease. Paul Emery concluded that remission is a realistic goal, and that the COMET results lend support to the use of combination therapy early in active RA. Tocilizumab in RA patients with an inadequate response to DMARDs TOWARD study confirms tocilizumab, an anti-il-6 receptor monoclonal antibody, is effective and has a favorable risk/benefit profile with background DMARDs Results from a large study in the US and Europe examined the efficacy and safety of tocilizumab (TCZ), a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, in patients with moderate to severe active RA were presented at the ACR meeting (Abstract SAT L15). The subjects enrolled in this trial had an inadequate response to a range of disease-modifying antirheumatic drugs (DMARDs). The TOWARD (Tocilizumab in Combination with Traditional DMARD Therapy) study, presented by Mark Genovese from Stanford University School of Medicine (CA, USA), 3

4 Table 4. Number of patients achieving (%) DAS28 remission and low disease activity at week 52 in the COMET trial. MTX ETN + MTX p value ACR20 163/243 (67) 220/256 (86) <0.001 ACR50 119/243 (49) 181/256 (71) <0.001 ACR70 69/243 (28) 124/256 (48) <0.001 ETN: etanercept; MTX: methotrexate. Table 5. ACR responses at week 24 in the TOWARD trial. Tocilizumab Placebo p value ACR < ACR < ACR < Table 6. Radiographic progression at week 24 in the RAPID-2 trial. Placebo CZP 200 mg CZP 400 mg (n=127) (n=246) (n=246) Change from baseline mtss 1.2 (4.1) 0.2 (2.7); 0.4 (2.1); Mean (SD) p=0.003 p<0.001 Erosion score 0.7 (2.6) 0.1 (2.0); 0.3 (1.8); Mean (SD) p=0.005 p<0.001 Joint space narrowing 0.5 (2.3) 0.1 (1.4); 0.1 (1.0); Mean (SD) p=0.004 p=0.004 CZP: certolizumab; mtss: mean total Sharp score; SD: standard deviation. showed that TCZ is effective in reducing articular and systemic symptoms and has a favorable risk/benefit profile when combined with background DMARDs. TOWARD was a 24-week, Phase III, randomized (2:1), placebo-controlled study of 1216 patients with active RA despite treatment with one or more traditional DMARDs. Patients continued stable doses of DMARDs and received TCZ 8 mg/kg or placebo intravenously every 4 weeks. The average duration of RA was 9.8 years and the mean DAS28 was 6.7. At week 24, the ACR responses were significantly higher in the TCZ group compared to the placebo group (Table 5); a higher ACR20 was apparent at week 2 in the TCZ arm. Disease remission (DAS28 <2.6) was demonstrated in 30.2% of TCZ patients compared with 3.4% of patients treated with only DMARDs. The incidence of AEs was 72.8% and 61.1% in the TCZ and placebo groups, respectively (p value not reported). The most frequent AEs were upper respiratory tract infections (URTI; 8.4% and 6.8% for TCZ and placebo, respectively), nasopharyngitis (5.9% and 4.8%, respectively), headache (5.0% and 3.9%, respectively), and hypertension (5.0% and 2.7%, respectively). AEs leading to withdrawal were 3.9% versus 1.9% (TCZ versus placebo, respectively). Of the 8% of patients with elevated baseline alanine aminotransferase in each group, 1% of the TCZ group had transient elevation (>3 ULN) and one patient withdrew from the study. Significantly elevated total cholesterol and LDL levels were reported for the TCZ group (total cholesterol: 22.9% vs 5.6% for TCZ vs placebo, respectively, LDL cholesterol: 16.1% vs 3.4%, respectively). The ApoB/ApoA atherogenic index was unchanged. Serious AEs were reported in 6.7% of TCZ patients and 4.3% of placebo patients, with serious infections in 2.7% of TCZ patients and 1.9% of placebo patients. Certolizumab pegol with MTX decreases joint damage RAPID-2 results show that certolizumab and MTX modify disease in active RA Results from the RAPID-2 study assessing the efficacy of two dosing regimens of liquid certolizumab pegol (CZP; a novel, PEGylated, Fc-free anti-tnf-α) in combination with MTX in patients with active RA and an incomplete response to MTX were presented by Désirée van der Heijde from University Hospital of Maastricht in The Netherlands. The results showed that liquid CZP 200 or 400 mg every 2 weeks added to MTX was significantly more effective in decreasing progression of structural joint damage compared with placebo + MTX over 24 weeks of treatment. The RAPID-2 study was a Phase III, double-blind, randomized, placebo-controlled, 24-week study that randomized 619 patients. Patients received MTX with one of two CZP doses (400 mg at baseline and weeks 2 and 4, then 200 mg or 400 mg every 2 weeks) or placebo in a 2:2:1 ratio. Those who failed to achieve an ACR20 response at both weeks 12 and 14 were eligible to enter an open-label follow-up study at week 16. Patients on placebo, CZP 200 mg or 400 mg had a mean Total Sharp Score (mtss) at baseline of 47.2, 40.2, and 48.2 Sharp units and a mean estimated yearly progression of 9.3, 7.5, and 8.2 Sharp units/year, respectively. Four-fifths (79%) of the placebo group compared with 19.7% in the CZP groups entered open-label treatment after 16 weeks due to lack of efficacy. Radiographic 4 JAN 2008 Rheumatology Highlights

5 progression results are detailed in Table 6. The investigators said that half the effect on radiographic progression was related to Psoriatic Arthritis Promising results for a human IL-12/23 monoclonal antibody in PsA First demonstration of targeting IL-12/23 in treating inflammatory arthritis A multicenter, randomized, double-blind, placebo-controlled proof of concept study has demonstrated that CNTO 1275, a fully human anti-il-12/23 monoclonal antibody, might be an effective and safe treatment for active psoriatic arthritis (PsA). Presenting results from the study, Alice Gottlieb from Tufts-New England Medical Center (Boston, MA, USA), said treatment with CNTO 1275, administered as four weekly doses, reduced the signs and symptoms of arthritis and associated psoriatic skin lesions in patients with PsA. In the study, patients were randomized to receive either CNTO mg/63 mg Juvenile Arthritis Abatacept and adalimumab show promise in juvenile arthritis New safety data in juvenile idiopathic arthritis biologics treatment A safety report of the use of abatacept in juveniles with active, treatment-resistant polyarticular juvenile idiopathic arthritis (JIA) suggests that the drug appears to be well tolerated in this patient population (Abstract THU 680). Another presentation of data from an extension of a Phase III study of adalimumab in juveniles with polyarticular JIA confirmed the long-term efficacy of this biologic in the treatment of JIA. the erosion score and half related to joint space narrowing; the mean change from baseline in the 400 mg group of 0.4 mtss (n=76) at weeks 0, 1, 2, and 3 followed by placebo at weeks 12 and 16 or placebo at weeks 0, 1, 2, and 3 followed by CNTO mg at weeks 12 and 16 (n=70). More patients (42.1% vs 14.3%; p<0.001) achieved an ACR20 response at week 12 in the CNTO 1275 group. Moreover, a higher proportion of patients in the CNTO 1275 group achieved an ACR50 (25% vs 7.1%; p=0.004) and an ACR70 (10.5% vs 0%; p=0.005) than placebo-treated patients. Health assessment questionnaire (HAQ) scores at week 12 were also significantly greater in the CNTO 1275 group (mean change 0.31 vs 0.04; p<0.001) than in the placebo-treated group. The 84.9% of patients with at least 3% body surface area psoriasis involvement who received CNTO 1275 had a greater decrease in the Dermatology Life Quality Index (mean change: 8.6) at week 12 than did patients receiving placebo ( 0.8; p<0.001). A larger In the abatacept study, 190 patients who had failed prior anti-tnf therapy were enrolled and entered a 4-month, open-label lead-in period. Following this, responders (170) were randomized 1:1 to double-blind therapy with abatacept or placebo every 28 days for up to 6 months. Patients randomized to the placebo group compared to the abatacept group demonstrated disease flare more frequently (53% vs 20%, respectively). An ACR Pediatric 90% response was seen in 40% of those who received abatacept for the 10 months of the study. During the open-label lead-in, six patients reported units may reflect repair, they claimed. proportion of patients treated with CNTO 1275 also achieved 75% improvement in the Psoriasis Area and Severity Index score at week 12 than did patients receiving placebo (52.4% vs 5.5%; p<0.001). There were no serious AEs through week 12 in the CNTO 1275 group versus three events in the placebo group. The proportion of patients with at least one AE was similar between patients receiving CNTO 1275 and placebo (60.5% vs 60%). The modified ACR responses at week 12 were lower than reported with anti-tnf agents. The lower response may reflect contrasting mechanisms in the skin and joint or, alternatively, a difference in the study design and dosing regimen compared to the CNTO 1275 psoriasis trial. 1. Krueger GG, Langley RG, Leonardi C et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 2007;356: serious AEs; three were considered to be related to underlying disease (two cases of flare and one case of joint replacement). There was also one case of varicella infection, one case of ovarian cyst, and one case of acute lymphocytic leukemia, diagnosed at day 89 in a patient who was anemic on enrollment. AEs were reported in 70% of patients; the most common were headache (13.2%), nausea (10%), cough (8.9%), diarrhea (8.9%), URTI (7.4%), and pyrexia (6.3%). Other than URTI, there were few infectious AEs and no opportunistic infections. Eight (4.2%) patients experienced acute infusional AEs; 5

6 the lead investigator (Daniel Lovell, Cincinnati Children s Hospital Medical Center) reported that none of these were serious. No serious AEs were reported in the abatacept group in the double-blind period but three were reported for the placebo-treated group. The overall frequency of all adverse events was similar in the two treatment groups. Infusion reactions were reported in 1.7% versus 3.2% of the abatacept and placebo groups, respectively; all three were reported as mild/moderate in intensity. No serious infections, autoimmune disorders, or anaphylaxis episodes were reported in any period. No consistent patterns of Fracture Zoledronic acid prevents fractures in men and women HORIZON-RFT shows for first time that anti-resorptive agent reduces mortality rate Results from the HORIZON Recurrent Fracture Trial were presented at the meeting and published in the NEJM [1]. The trial demonstrated that an annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture is associated with a reduction in the rate of new clinical fractures and improved survival; Kenneth Lyles, Duke University Medical Centre, NC, US). In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (5 mg), and 1062 patients were assigned to receive placebo. Infusions were first administered within 90 days after surgical repair of a hip fracture and the median follow-up was 1.9 years. All patients, whose mean age was 74.5 years and 76% of whom were women, received supplemental vitamin D (loading dose of D 2 or D 3 and daily supplements of IU vitamin D 3 ) and calcium ( mg elemental calcium). abnormal liver/kidney function tests or hematological parameters emerged. In the adalimumab study (also led by Dr Lovell), 171 patients with active JIA were enrolled in a multicenter Phase III study. During the initial open-label period (16 weeks), patients received adalimumab at a dose equivalent to the approved adult dose adjusted for the height and weight of a child. Responders (ACR Pediatric 30% response) were stratified by MTX use and randomized to receive either adalimumab or placebo for 32 weeks or until disease flare. Patients could then choose to enter the body surface area-dosed open-label extension (BSA-OLE) study. Patients were followed up until 211 had experienced confirmed new clinical fractures (primary efficacy endpoint). The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (p=0.0012); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (p=0.02), and the respective rates of new non-vertebral fractures were 7.6% and 10.7% (p=0.03). The overall incidence of AEs and serious AEs was comparable between the treatment groups. The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of jaw osteonecrosis were observed. No significant differences were reported in any cardiovascular parameters or long-term renal function. In the zoledronic acid group, 101 of 1054 patients (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic acid group (p=0.01). 1. Lyles K, Colón-Emeric CS, Magaziner J et al. Zoledronic acid and clinical fractures and mortality after hip fracture. NEJM 2007;357: The results showed that, at week 16, 84% of patients achieved an ACR Pediatric 30% response, 77% achieved an ACR Pediatric 50% response, 58% achieved an ACR Pediatric 70% response, and 27% achieved an ACR Pediatric 90% response. After the 32-week, placebo-controlled period, patients receiving adalimumab had significantly fewer flare-ups compared to the placebo group. Of the 128 patients who entered the BSA-OLE, 75% had observed data available after 1 year of treatment. Response to adalimumab was sustained. The safety profile during the OLE was reported as similar to that observed in previous study periods. Adherence to bisphosphonates Longitudinal study of adherence assesses impact on hip fractures Poor adherence to bisphosphonates is associated with a greater rate of fracture. A study from the University of Alabama based on claims data identified persons initiating bisphosphonates and calculated adherence as a Medication Possession Ratio (MPR), allowing for bisphosphonate switching. Adherence among individuals initiating weekly versus daily bisphosphonates was compared and MPR was examined at 1, 2, and 3 years and compared with hip fracture rates. There were new bisphosphonate users identified with 1 year of follow-up. The proportion with MPR 80% was 44%, 39%, and 36% at 1, 2, and 3 years, respectively. Among persons with MPR 80% at year 1, 80% of these had MPR 80% at year 2. Those who were initially prescribed weekly bisphosphonates had higher 1 year MPR than those initially prescribed daily bisphosphonates (mean = 45% vs 38%; p<0.001). Among those with a hip fracture, MPR at years 1, 2, and 3 was 9%, 12%, and 10% lower, respectively, compared to those without 6 JAN 2008 Rheumatology Highlights

7 a hip fracture (p<0.001). The MPR in the 3 and 6 months following a hip fracture was 9% and 6% compared to before the hip fracture (p< and p<0.0001, respectively). The researchers concluded NSAIDs that adherence at year 1 was a strong predictor of adherence in subsequent years. Adherence in the 3 and 6 months following a hip fracture was significantly lower than immediately prior to the fracture. Analyses that fail to consider adherence in a time-dependent fashion before fracture occurs, said the researchers, may magnify the apparent differences in fracture risk between adherent and non-adherent persons. Decreased gastroprotection and increased ulcer complications Retrospective study shows a sharp rise in serious GI complications in the elderly Reporting data from MediCal, the Medicaid program for California, Gurkirpal Singh from Stanford University Medical School said recent safety concerns and market shifts have resulted in an increasing number of elderly users of NSAIDs suffering serious gastrointestinal (GI) complications. Studying prescriptions for NSAIDs issued from January 1, 1997 to June 30, 2005, Singh and colleagues reported that in 1997, 79% of NSAID users with arthritis aged over 65 years were not prescribed concomitant gastroprotection; falling to only 14% in However, the proportion not receiving gastroprotection then rose to 35% in 2005, following a decline in COX-2 inhibitor use without a commensurate increase in other Table 7. The gastroprotection gap and serious ulcer complications. Year COX-2s PPIs Misoprostol Gastroprotection Serious ulcer (%) (%) (%) gap (%) complications (per NSAID prescriptions) NSAID: non-steroidal anti-inflammatory drug; PPIs: proton pump inhibitors. gastroprotective therapies (Table 7). The rate of serious GI complications dropped from 682 per prescriptions in 1997 to 357 in 2004 (p<0.001). The sharpest decline was seen from 1999 to 2000 (579 to 423), corresponding with a large decline in those not receiving gastroprotection (55.6% to 25.2%). As the gastroprotection gap increased, reported Singh, a sharp rise in serious GI complications from 357 to 434 (21%; p<0.0001) was observed. Systemic Lupus Erythematosus Monitoring for interferonregulated chemokines in SLE Study suggests that monitoring IFN-regulated chemokines may be a useful tool Data presented by Jason Bauer from the University of Minnesota suggest that chemokine levels are reliable biomarkers of current disease activity in systemic lupus erythematosus (SLE), outperforming standard laboratory tests. Bauer and his team used multiplexed sandwich-based immunoassays to analyze serum samples from 288 SLE patients followed longitudinally for a year. The results showed that levels of interferoninducible protein 10 (IP-10) increase with flare (p= ) and decrease with remission (p= ) and that this and the chemokine score (flare p= ; remission p= ) were significantly higher markers of current activity, while classic laboratory tests did not attain the same level of significance (flare p>0.3; remission p=0.01). Baseline chemokine levels also predicted future activity, such that patients with high chemokine levels at baseline were more likely to have an active future disease course as measured by the SLEDAI (SLE Disease Activity Index; p= ). Dr Bauer suggested that monitoring interferon-regulated chemokine levels may provide a reliable measure of disease activity for use in clinical trials. 7

8 Rheumatology Highlights ACR 2007 Continuing Medical Education One answer is correct for each question. 1. What percentage of ankylosing spondylitis suffers experience an episode of anterior uveitis? A. 0 20% B % C % D % E % 2. In the RHAPSODY trial, by what proportion did adalimumab reduce the rate of uveitis flares? A. ~5% B. ~10% C. ~25% D. ~33% E. ~50% 3. Which of the following statements is not true about the COMET trial? A. The endpoint of the trial is remission. B. The trial compares the effects of MTX alone with etanercept + MTX. C. Participants have active early rheumatoid arthritis. D. By 12 months, a greater clinical benefit was observed in patients receiving combination therapy than in those receiving single-drug treatment. E. In the first 12 months of the trial, serious adverse events were reported by a higher proportion of patients receiving combination therapy than single-drug treatment. 4. Which of the following is true about tocilizumab: A. Tocilizumab is an anti-tnf monoclonal antibody. B. Tocilizumab is a humanized anti-il-6 antibody. C. Tocilizumab is a humanized polyclonal antibody. D. Tocilizumab is an anti-il-6 receptor antibody. E. None of the above. 5. Which of the following statements regarding treatment of psoriatic arthritis patients with the anti-il-12/23 antibody CNTO 1275 is correct? A. At 12 weeks following the start of treatment, patients exhibit a significant improvement in the PASI score but no change in HAQ scores. B. At 12 weeks following the start of treatment, patients exhibit a significant improvement in the PASI and HAQ scores. C. At 12 weeks following the start of treatment, patients exhibit a significant improvement in HAQ scores but no improvement in the PASI score. D. Patients exhibit significant improvements in PASI, HAQ, and Dermatology Life Quality Index scores at week 24 following the start of treatment, but improvements are not apparent at week 12. E. At 12 weeks following the start of treatment, adverse events were reported significantly more frequently in CNTO 1275-treated individuals, compared with placebo. 6. In an analysis of the safety of abatacept in pediatric patients with polyarticular juvenile idiopathic arthritis serious adverse events were reported in: A. >5% B. 12% C. 20% D. 70% E. No subjects 7. Which of the following statements is true of the findings of the HORIZON Recurrent Fracture Trial? A. Infusion of zoledronic acid every 90 days after repair of low-trauma hip fracture reduced the rate of new clinical fractures. B. Rates of adverse effects were not comparable between treatment groups. C. Patients who received adalimumab had significantly fewer flare-ups compared with those receiving placebo. D. Annual infusion of zoledronic acid was not associated a reduction in the rate of new clinical fractures, compared with placebo. E. Annual infusion of zoledronic acid was associated a reduction in the rate of new clinical fractures, compared with placebo. 8. One of the following statements is not true of the study findings reported by Kenneth Lyles et al. Which is it? A. Pyrexia was a frequent adverse effect of zoledronic acid treatment. B. The primary efficacy endpoint was the confirmation of new clinical fractures in 211 patients. C. Jaw osteonecrosis was observed in one of the patients. D. Patients were more likely to die from any cause if they received placebo rather than zoledronic acid. E. The proportion of patients experiencing a clinical fracture was significantly higher in the placebo group. 9. Interferon-regulated chemokine levels are reliable biomarkers of current disease activity in SLE. A. True B. False 10. Levels of interferon-inducible protein 10 in patients with SLE: A. Decrease with flare and increase with remission. B. Increase with flare and decrease with remission. C. Decrease longitudinally. D. Remain stable.

9 Rheumatology Highlights ACR 2007 Continuing Medical Education Response Form Complete the post-test answer sheet, evaluation form, and registration form and return to: Attn: Distance Education [XEN08138] University of Kentucky College of Pharmacy and Medicine Continuing Education Office One Quality Street, 6th Floor Lexington, KY 40507, USA You can also participate online by going to and entering the activity code [XEN08138]. Examination answers Record your answers here by filling in the blank with the correct letter for the corresponding question: Participants will receive a confidential report of their results along with the correct answers to each question. A certificate of credit will be sent to those who successfully complete the examination. EVALUATION FORM Strongly agree Strongly disagree 1. The activity provided new information I had not yet acquired The activity helped increase my knowledge and skills The activity content was educational and understandable The activity content met its objectives The amount of information presented was adequate for my needs I felt I absorbed a reasonable amount of the presented materials The technical quality of the activity was acceptable I would recommend this program to my peers Funding for this activity may have come from commercial sponsors. Do you think you were adequately informed of commercial sponsorship or faculty conflict of interest? Yes No 10. Do you think the overall activity was biased toward certain commercial products or services? Yes No REGISTRATION FORM Name:... Affiliation:... Office Address: City:... State:... Zip Code:... Office Phone:... Home Phone: Physician License No./State:... By signing this certificate, I attest that I have attended the above named continuing medical education program. Signature:... Credit Hours:...

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