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BSR AND BHPR PLENARY ORAL PRESEN

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					                                              Wednesday 21 April 2010, 09:00-10:30


  BSR AND BHPR PLENARY ORAL PRESENTATION OF
                  ABSTRACTS

           BSR and BHPR Plenary Oral                                        OP2. METHOTREXATE IS NOT DISEASE MODIFYING IN
                                                                            PSORIATIC ARTHRITIS: A NEW TREATMENT PARADIGM IS
                                                                            REQUIRED
                                                                            Gabrielle H. Kingsley1, Jonathan C. Packham2, Neil J. McHugh3,
OP1. USE OF CONSERVATIVE AND                                                Diarmuid M. Mulherin4, George D. Kitas5, Kuntal Chakravarty6,
SURGICAL FOOT CARE IN RHEUMATOID                                            Fowzia Ibrahim1, Helen Taylor1, Anna Kowalczyk1, Peter J.
ARTHRITIS: THE ERAS COHORT                                                  Maddison7 and David L. Scott1
                                                                            1
                                                                              Rheumatology, King’s College London, London, UK;
Michael R. Backhouse1, Anne-Maree Keenan2,                                  2
                                                                              Rheumatology, Haywood Hospital, Stoke on Trent, UK;
Adam Young3, David James3, Nigel Cox3, Peter Williams3, R. Musa3,           3
                                                                              Rheumatology, Royal National Hospital for Rheumatic Diseases,
Philip S. Helliwell1 and Anthony C.65 Redmond1                              Bath, UK; 4Rheumatology, Cannock Chase Hospital, Cannock, UK;
1                                                                           5
  Section of Musculoskeletal Disease, University of Leeds, Leeds, UK;         Rheumatology, Russells Hall Hospital, Dudley, UK; 6Rheumatology,




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2
  NIHR Biomedical Research Unit, University of Leeds, Leeds, UK;            Queens Hospital, Romford, UK; 7School of Medical Science,
3
  ERAS Department of Rheumatology, City Hospital, St Albans, UK             University of Bangor, Bangor, UK
Background: While 90% of people with rheumatoid arthritis (RA)              Background: Methotrexate (MTX) is widely used in psoriatic arthritis
experience foot problems, UK rheumatologists have expressed                 (PsA). By consensus, it is considered a ‘‘disease modifying’’ drug
concerns as to poor availability of foot health services. Uptake of         (DMARD) though systematic reviews show no evidence for this. We
patients with RA using foot care has yet to be explored.                    report the results of the arc-funded Methotrexate In Psoriatic Arthritis
Methods: The Early RA Study (ERAS) is an inception cohort collecting        (MIPA) Trial—the only large multicentre randomized controlled trial
data from 9 centres in England from 1986 to 1998. Exploratory analysis      (RCT) of MTX in active PsA.
was performed on the data set to identify use of podiatry and foot          Methods: MIPA was a double-blind RCT comparing 6 months MTX
surgery at 3,5,7 and 9 years after onset of RA.                             (15 mg/week) with placebo in active PsA patients. The primary
Results: Data were collected for 1237 patients with early RA [66.9%         outcome was PsA Response Criteria (PsARC) at 6 months analysed
female, mean age at disease onset ¼ 54.36 years (S.D. ¼ 14.18), median      on an intention to treat (ITT) basis. Secondary outcomes included
DAS ¼ 4.09, (IQR ¼ 3.04 to 5.26)]. Follow up data were available for        tender and swollen joint counts, patient and assessor global
55% (n ¼ 680) at 9 years, 57% (n ¼ 538) 91% (n ¼ 1122) and 100%             assessments, pain, HAQ, ESR and CRP.
(n ¼ 1237) at 7, 5 and 3 years, respectively. 82% (n ¼ 1012) had ever       Results: 221 patients were enrolled comprising 97 females and 124
been RF positive, 79% (n ¼ 974) ever had X-ray detected erosions and        males, mean age 49 years (S.D. 12) and median disease duration
34% (n ¼ 425) ever had rheumatoid nodules.                                  5 years (S.D. 7). 67/109 (61%) of the MTX group and 61/112 (54%) of
    Only 36% (n ¼ 444) of patients received foot care, of these 82%         the placebo group completed 6 months of therapy. Patients withdrew
(n ¼ 364) received this from a podiatrist with the remainder receiving      from MTX and placebo arms for adverse events (12% vs 9%) and other
care from orthotists. Those who received podiatry treatment had an          reasons (26% vs 37%) including lack of effect. On ITT analysis,
older age of onset of RA (mean 59.1 years, 95% CI 57.8 to 60.4 years)       6 month PsARC responses occurred in 43/109 (39%) patients on MTX
than those who did not access podiatry treatment (mean 52.2 years,          and 30/112 (27%) on placebo (P ¼ 0.063 by Fisher’s Exact Test).
95% CI 51.3 to 53.2 years). Female patients were more than twice as         6-month completers showed similar effects (51% vs 33%; P ¼ 0.049).
likely to access podiatry (OR 2.42 95% CI 1.81 to 3.22). In contrast to     There were no significant differences at 3 months. Comparisons of
the other treatments, 15% (n ¼ 190) of patients who were seen by an         individual measures at 6 months (Table) showed MTX only gave
orthotist were more likely to be seen by a podiatrist (OR 4.33 95% CI       significant benefits for assessor and patients global responses
3.13 to 5.97) and have foot surgery (OR 4.26 95% CI 2.58 to 7.03). Only     (P ¼ 0.01 and P ¼ 0.003 by Rank Sum test); joint counts, ESR, CRP,
1.7% (n ¼ 21) of patients were reported as having lower limb related        HAQ and pain assessments were not significantly different. Analysis of
appliances at any time during the follow up period.                         completers was similar.
    101 foot and ankle operations were performed on 71 (6%) patients,       Conclusions: MTX had a borderline effect on PsARC due to
68 of which were MTP joint procedures. Only 9 procedures were               improvement in symptomatic measures (patient and assessor global)
reported for the ankle or hind foot and 24 soft tissue procedures of foot   but not for those (joint swelling, acute phase response) generally
or hind foot were noted. Time to patients having their first operation      considered to indicate disease modification. This suggests that in PsA,
ranged from 7 to 221 months, with a mean of 88 months. Patients             MTX is a ‘‘slow-acting symptom modifier’’ not a DMARD. These
undergoing surgery had a younger age of onset of RA (mean 47.8              findings are similar to sulfasalazine but contrast with the definite
years 95% CI 44.9 to 50.7 years) than those who did not (mean 54.7          DMARD status of leflunomide and tumour necrosis factor inhibitors.
years 95% CI 53.9 to 55.6 years). The mean age of patients at the time          As early disease modification in PsA is important, the use of a non-
of their first operation was 55.2 years (S.D. ¼ 12.4 years). Females were   DMARD is suboptimal and a new treatment pathway is required.
more likely than males to undergo any type of foot surgery (OR 2.09         Furthermore, the NICE PsA guidance which requires 2 DMARDs before
95% CI 1.15 to 3.79). Patients with erosions were more likely to have       starting tumour necrosis factor inhibitors needs revising as there do
MTPJ surgery (OR 4.26 95% CI 1.32 to 13.82) and those with nodules          not appear to be two DMARDs in PsA.
were more likely to have MTPJ (OR 2.05 95% CI 1.16 to 3.64) and soft
tissue surgery (OR 2.29 95% CI 0.92 to 5.68). Of the 71 patients who
                                                                            Initial variables and 6 month changes in MTX and placebo groups (median/IQR)
had foot surgery, 28 had never seen a podiatrist for conservative foot      analysed by ITT
care.
Conclusions: Despite the known high prevalence of foot pathologies          Variable          Initial values     6 month            6 month             P
in RA, only 1/3 of the ERAS cohort accessed podiatry. While older                                                change             change with
                                                                                                                 with MTX           placebo
females were more likely to access podiatry care and younger patients
surgical intervention, a large proportion of the RA population did not                        (n ¼ 221)          (n ¼ 109)          (n ¼ 112)
access podiatry.                                                            Assessor Global   40 (29 to 57)      13 (5 to 32)       5 (À4 to 25)        0.01
                                                                            Patient Global    48 (30 to 70)      16 (3 to 33)       6 (À17 to 23)       0.003
Disclosure statement: All authors have declared no conflicts of             Swollen Joints    6 (3 to 11)        3 (0 to 9)         1 (À1 to 5)         NS
interest.                                                                   Tender Joints     9 (5 to 17)        2 (0 to 6)         3 (À2 to 6)         NS
                                                                            HAQ               1.0 (0.5 to 1.5)   0.13 (0 to 0.63)   0 (À0.20 to 0.38)   NS
                                                                            Pain              40 (25 to 62)      8(À5 to 27)        5 (À10 to 25)       NS
                                                                            CRP               8 (5 to 17)        0 (À1 to 5)        0 (0 to 7)          NS
                                                                            ESR               14 (7 to 27)       4 (0 to 11)        2 (À2 to 6)         NS

                                                                            Disclosure statement: All authors have declared no conflicts of
                                                                            interest.
i2   Wednesday 21 April 2010, 09:00-10:30                                            BSR and BHPR Plenary Oral Presentation of Abstracts


OP3. BELIMUMAB, A BLYS-SPECIFIC INHIBITOR, REDUCED                                    Results: Mean baseline disease characteristics across treatment
DISEASE ACTIVITY, FLARES AND PREDNISONE USE IN                                        groups were similar: SLE disease duration 5.3 years; SS 9.8; BILAG
PATIENTS WITH ACTIVE SEROPOSITIVE SLE: PHASE 3                                        1A/2B 58%; ANA þ 95%; anti-dsDNA þ 75%; low C4 59%; proteinuria
BLISS-52 STUDY                                                                        (> 0.5 g/24 h) 25%; antimalarials 67%; prednisone ! 7.5 mg/d 69%;
                                                                                      immunosuppressants 42%. SRI response rates were 51% (P ¼ 0.0129)
David D’Cruz1, Coman Tanasescu2, Sandra Navarra3,                                     in the 1-mg/kg and 58% (P ¼ 0.0006) in the 10-mg/kg belimumab dose
Renato Guzman4, Alberto Gallacher5, Roger A. Levy6, Edmund                            groups (vs placebo 44%). Significant improvement was seen in at least
K. Li7, Mathew Thomas8, Renato E. Jimenez9, Manuel G. Leon10,                         one of the belimumab treatment groups for SS ! 4-point reduction;
Stephen Hall11, Joung-Liang Lan12, Ho-Youn Kim13, Lilia Pineda14,                     improvement or no > 0.3-point worsening in PGA; reduction in
John Zhong14 and William W. Freimuth14                                                prednisone use; reduction in flare rates and increase in time-to-first
1
  St Thomas’ Hospital, London, UK; 2Spitalul Clinic Colentina,                        flare (Table). The rates of overall AEs, deaths, serious AEs, infections
Bucharest, Romania; 3University of Santo Tomas Hospital, Manila,                      and lab abnormalities were comparable in the belimumab and placebo
Philippines; 4Saludcoop Clinic 104, Bogota, Colombia; 5Hospital                       groups. Serious or severe infusion reactions were modestly increased
Britanico, Buenos Aires, Argentina; 6Universidade do Estado do Rio
     ´                                                                                with belimumab compared with placebo. No malignancies were
de Janeiro, Rio de Janeiro, Brazil; 7Prince of Wales Hospital, Hong                   reported.
Kong, China; 8Kerala Institute of Medical Sciences, Trivandrum,                       Conclusions: In BLISS-52, belimumab significantly reduced SLE
India; 9Hospital Dr Gustavo Fricke, Vina del Mar, Chile; 10Instituto de
                                      ˜                                               disease activity, SLE flare rates and prednisone use and increased
Ginecologıa y Reproduccion, Lima, Peru; 11Cabrini Hospital,
           ´                ´                                                         time-to-first SLE flare in patients with active SLE. The overall rate of
                         12
Malvern, VIC, Australia; Veterans General Hospital, Taichung,                         AEs including serious AEs and infections were comparable in the
Taiwan; 13Catholic University, Yoido St Mary’s Hospital, Seoul,                       belimumab and placebo groups.
Korea, Republic of; 14Human Genome Sciences, Inc., Rockville,                         Disclosure      statement:      D.D.,   Human      Genome      Science/
MD, USA                                                                               GlaxoSmithKline - Trial Investigator. W.W.F., Human Genome
                                                                                      Sciences, Inc. - Employee. A.G., Human Genome Sciences -




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Background: To assess the efficacy and safety of belimumab in                         Consultation fees. R.E.J., HGS/GSK - Research grant. H.-Y.K., HGS/
patients with seropositive SLE.                                                       GSK - Trial Investigator. J.-L.L., HGS/GSK - Trial Investigator. M.G.L.,
Methods: 865 seropositive (ANA ! 1:80 and/or anti-dsDNA ! 30 IU/                      HGS/GSK - Trial Investigator. R.A.L., Roche - Speaker, Consultation
mL) SLE patients with SELENA-SLEDAI (SS) ! 6 (on stable standard of                   fees, grant, Wyeth - Honoraria, Speaker, BMS - Speaker, HGS/GSK -
care [SOC] therapy ! 30 days) were randomized and treated in this                     Speaker, Consultation fees, Research grant, Pfizer - Speaker,
phase 3, 52-week double-blind, international trial of belimumab (1 or                 Consultation fees, Research grant, Abbott - Speaker Consultation
10 mg/kg) plus SOC or placebo plus SOC on d 0, 14, 28, then every 28                  fees. S.N., Roche - Speaker Bureau, Wyeth - Speaker Bureau,
days for 48 weeks. Efficacy analyses included SS, BILAG and SS Flare                  Schering Plough - Speaker Bureau. L.P., Human Genome Scinces,
Index (SFI). The primary endpoint was the week 52 SLE Responder                       Inc. - Employee, Stock. C.T., HGS/GSK - Trial Investigator. J.Z.,
Index (SRI): improvement in SS (! 4-point decrease), no new BILAG A                   Human Genome Sciences, Inc. - Employee. All other authors have
or 2 B flares and no > 0.3-point worsening in Physician’s Global                      declared no conflicts of interest.
Assessment (PGA) vs baseline.



                                                               Placebo                     Belimumab                                  Belimumab
                                                               n ¼ 287                     1 mg/kg                                    10 mg/kg
                                                                                           n ¼ 288                                    n ¼ 290
Efficacy SRI at week 52Ã , n (%)                               125 (44)                    148 (51)                P value            167 (58)                P value
                                                                                                                   0.013                                      0.0006
 SS ! 4-point reduction                                       132 (46)                    153 (53)                0.019              169 (58)                0.0024
 No PGA > 0.3-point worsening                                 199 (69)                    227 (79)                0.0078             231 (80)                0.0048
 No new BILAG 1A/2B scores                                    210 (73)                    227 (79)                0.086              236 (81)                0.018
% PGA improvement at week 24, mean (SE)                        22 (2.6)                    30 (2.2)                0.034              37 (2.4)                < 0.0001
Prednisone reduction from > 7.5 mg/day by 25% from             23 (12)                     42 (21)                 0.025              38 (19)                 0.053
baseline or to 7.5 mg/day during weeks 40-52, n (%)
Prednisone increase from 7.5 mg/day to > 7.5 mg/d              34 (36)                     25 (30)                 0.56               17 (20)                 0.020
at week 52, n (%)
                                                                                                                            y
SFI flare, % (hazard ratio [HR]) Median time to first          80 84                       71 (0.75) 126           0.0026             71 (0.76) 119           0.0036y
flare, day
 Severe SFI flare                                             23                          18 (0.76)               0.13               14 (0.57)               0.0055
New BILAG 1A/2B flare, % (HR)                                  30                          27 (0.89)               0.48               19 (0.58)               0.0016
Safety, n (%) AEs/Serious AEs                                  263 (92) / 36 (13)          264 (92) / 47 (16)                         266 (92) / 41 (14)
Infections/Serious infections<i/>                              183 (64) / 17 (6)           197 (68) / 22 (8)                          194 (67) / 13 (5)
Infusion reactions/Hypersensitivity                            49 (17) / 1 (<1)            47 (16) / 4 (1)                            48 (17) / 2 (1)
Discontinuations/Due to AEs                                    61 (21) / 19 (7)            48 (17) / 16 (6)                           49 (17) / 15 (5)
Ã
 Patients who withdrew from the study prior to week 52 visit or who used protocol-prohibited medications were considered treatment failures. yP-values were obtained by
the Cox proportional hazard model for time to first flare.

				
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