BSR guidelines for prescribing TNF-a
blockersin adults with ankylosing spondylitis. Report of aworking party of the British Societyfor Rheumatology
A. Keat, N. Barkham1, A. Bhalla2, K. Gaffney3, H. Marzo-Ortega1,S. Paul4, F. Rogers5, M. Somerville3, R. Sturrock6 and P. Wordsworth7on behalf of the BSR Standards, Guidelines and Audit Working Group
Two TNF-blocking drugs are now licensed for the treatment of
the prevalence of AS ranges from 0.05  to 0.23%  in adults,
ankylosing spondylitis (AS) and there is clear evidence of
men being affected 3–4 times more frequently than women, and
symptomatic efﬁcacy. It is recognized that the instruments for
in Rochester, Minnesota, an annual incidence rate of 7.3 per
analysing aspects of AS and the outcomes of treatment are
100 000 person years has been calculated . The prevalence of
imperfect, though they are validated and adequate for the purpose.
AS and HLA-B27 within different ethnic populations has been
This document provides guidance to enable consultant
rheumatologists in the UK to balance the demonstrated merits
In a community with a population of 500 000 adults,
of TNF blockade treatment against the known and unknown
approximately 500–1000 cases may be expected. Currently
some patients with AS do not seek hospital care. Some ofthese have mild symptoms. Others have ceased to attendhospital
The availability of new and effective treatment may well
AS is an inﬂammatory condition primarily affecting the spine.
inﬂuence the number of AS sufferers who seek hospital
Onset is most common in the third decade of life, though the
disease may remain symptomatic and progressive throughout life.
It is part of the family of spondyloarthropathies, which also
includes psoriatic arthritis, reactive arthritis and enteropathicarthritis. Undifferentiated forms of spondyloarthopathy, often
Individuals with AS suffer pain and disability comparable to that
presenting as mono- or oligoarthritis, are also recognized, as
of patients with rheumatoid arthritis . Because the onset of AS
are juvenile forms of spondyloarthopathy, in which the spine is not
is typically earlier than that of rheumatoid arthritis, the impact
affected but may become so later. Thus, many individuals with AS
of these social and economic factors is felt at a younger age.
also suffer from involvement of the hips, peripheral joints and
Up to 50% of patients with adult-onset AS and a higher
peripheral entheses as well as periodic eye inﬂammation,
proportion of those with juvenile onset develop hip arthritis,
inﬂammatory bowel disease and psoriasis. The treatment of axial
and many of these will undergo hip replacement surgery ;
and peripheral elements of this disease therefore requires distinct
a minority of patients will also require surgery to other
criteria and guidance that is speciﬁc for the particular feature.
joints, especially the knees. Because of heterotopic ossiﬁcation
Symptoms may persist throughout adult life, though some
as well as younger age at the time of surgery, revision of
patients experience a diminution of symptoms or even remission
hip replacements is more often necessary than when this procedure
of active disease after a period of years. The consequences of
is performed for other indications. A minority of patients also
active spinal disease, including spinal stiffness or rigidity and
undergo spinal surgery because of severe deformity or spinal
increased risk of spinal fracture, are irreversible.
fracture. Osteoporosis occurs early in disease and contributes tothe increased susceptibility to spinal fracture later in life [9, 10].
Life expectancy for people with AS is reduced; the standard-
Prevalence and incidence of ankylosing spondylitis
ized mortality ratio is 1.5 [11, 12]. The excess mortality is
Susceptibility to AS is inﬂuenced by genetic factors, particularly
mainly accounted for by cardiac valvular disease, amyloidosis
HLA-B27 [1, 2]. Thus, the population prevalence of HLA-B27
and fractures. As a consequence, people with AS bear higher
inﬂuences the population prevalence of AS. In Caucasians,
personal insurance costs than the healthy population.
Northwick Park Hospital, Harrow, 1Leeds General Inﬁrmary, Leeds, 2RNHRD, Bath, 3Norfolk and Norwich Hospital, Norwich, 4St Thomas’ Hospital,London, 5National Ankylosing Spondylitis Society, Mayﬁeld, 6University of Glasgow and Glasgow Royal Inﬁrmary, Glasgow and 7University of Oxfordand Nufﬁeld Orthopaedic Centre, Oxford, UK.
Submitted 20 August 2004; revised version accepted 29 March 2005.
Published on the British Society for Rheumatology website in July 2004.
Correspondence to: A. Keat, Arthritis Centre, Northwick Park Hospital, Harrow, Middlesex, AAI 30J, UK. E-mail: [email protected]
Published by Oxford University Press on behalf of the British Society for Rheumatology 2005.
about appearance (51%), worry about the future (50%) andmedication side-effects (41%).
Studies using the SF-36 (SF-36 Health Survey: Medical
The impact of AS on employment status is signiﬁcant .
Outcomes Trust Inc.) showed that quality of life for AS sufferers
In a Dutch study, overall participation in the labour force
was poor, especially in the physical component, ﬁgures being
was 54.2% for the AS cohort, a signiﬁcant reduction of 11%
worse than some published data for rheumatoid arthritis
compared with the general population of the same working
and even for some cancers . This is also reﬂected in poor
age . More than three-quarters of patients with AS who had
AS-speciﬁc quality of life assessment, ASQoL .
stopped working were ofﬁcially recognized as work-disabled.
Approximately one-third of individuals with AS give up
work prematurely on health grounds, and an additional 15%
suffer constraints within work, including reduction in hoursworked and a change of job, as a result of the disease. Work
Traditionally, treatment of AS has been directed to relieving
disability is associated with being older, longer duration of
pain and stiffness in an attempt to preserve mobility and
maintain function. Regular physiotherapy and the use of
physical impairment, pain, fatigue, stiffness, anxious and
non-steroidal anti-inﬂammatory agents (NSAIDs) form the
depressed mood, and lower self-esteem .
mainstay of treatment. NSAIDs have a quick symptomaticeffect, providing in most cases rapid improvement within 48 hafter intake and leading to rapid relapse after their discontinua-
tion . This is true to the extent that it has been suggested
that, for patients with back pain, the probability of suffering
AS carries a signiﬁcant economic burden, arising from the
from AS is as low as 3% if there is a failure to respond to
direct costs of medical care and disability care, and from the
NSAIDs . There is, however, no clear indication that their
indirect costs associated with loss of earnings and reduced
long-term use alters the structural progression of the disease.
This, together with the known risk of side-effects (mainly
A prospective longitudinal study of 241 patients with AS 
gastrointestinal), has translated into these drugs being used
in the majority of patients for clinical relapses rather than as
diagnostic tests, ambulatory care visits, assistive devices, travel,
a continuous therapy. The advent of the new cyclooxygenase
paid household help and other treatments) and annual indirect
2 (COX-2)-speciﬁc inhibitors, thought to be as efﬁcacious as
costs (work days missed or, for retirees, days of limited activity).
conventional NSAIDs , may challenge this view.
Patients had a mean duration of disease of 20 yr. All patientswere assessed for 1 yr, with a subset of 111 patients followedup for 5 yr. Functional disability was measured using the
Instruments for the diagnosis and assessment of AS
Health Assessment Questionnaire disability index, modiﬁed
The diagnosis of AS is made according to the modiﬁed
25-question self-report instrument that asks respondents to
The most widely used measure of the inﬂammatory activity of
assess functional difﬁculty in 10 areas (dressing, arising, eating,
AS is the Bath Ankylosing Spondylitis Disease Activity Index
walking, hygiene, reaching, gripping, errands and chores,
(BASDAI) . This simple instrument is patient-completed,
bending, and driving). The range for each question is from
sensitive to change over 3 weeks, and has been validated. Some
0 (no difﬁculty) to 3 (unable to do) and the scores are averaged
studies have used the two BASDAI spinal stiffness scores as
measures of spinal inﬂammation. Several investigators have
In the 1-yr follow up, annual total costs averaged US$6720,
included a visual analogue score (VAS) of spinal pain within the
direct costs contributing 26% of total costs. These ﬁgures
last week as a measure of active disease, as the BASDAI does
were similar in the 5-yr cohort. In contrast, studies of the
not specify this as a single criterion. Since measures of the acute-
direct and indirect costs of rheumatoid arthritis have suggested
phase response are not indicative of the activity of spinal disease,
that indirect costs are comparable to or lower than direct
these have not been included in this guideline.
costs [16, 17]. The larger contribution of indirect costs in
Response to treatment has been gauged primarily by two
AS may reﬂect the younger age of patients, who may experience
measures in clinical trials. The reduction in the BASDAI
work disability for a longer proportion of their working years.
has been shown to be simple and sensitive. Fifty per cent
Functional disability was the most important indicator of
reduction in the BASDAI (BASDAI 50) has been suggested as
high total costs and direct costs among these patients. In the
an appropriate treatment outcome by the Assessments in
1-yr study, the risks of having high total costs (>$10 000/yr)
Ankylosing Spondylitis (ASAS) Working Group. They have
increased by a factor of 3 with each 1-point increase in the
also recommended that signiﬁcant clinical beneﬁt is indicated
HAQ-S score. Results were similar in the 5-yr follow up cohort,
by reduction of the BASDAI by 50% or a fall of 2 units .
where the likelihood of high costs (>$50 000 over 5 yr) was
Earlier deliberations of the ASAS working group concluded that
increased by >6 with each 1-point increase in HAQ-S. The
a response to treatment should be assessed according to a
authors concluded that interventions that reduce functional
composite score, including VAS scales reﬂecting pain, inﬂam-
disability would be anticipated to be the most effective means
mation, well-being and function . Improvement in three
modalities by 20% or more, without deterioration in the fourthmodality, constitutes an ASAS 20 response. Improvements of50 and 70% in three modalities constitute ASAS 50 and 70responses, respectively. Current clinical studies indicate compar-
able performance of the ASAS combined score and the BASDAI
Quality of life has been shown to be adversely affected by AS
50 or a fall of !2 units in assessing response to treatment.
. The most prevalent quality of life issues related to stiffness
Expert opinion has been recommended by the ASAS group
(90%), pain (83%), fatigue (62%), poor sleep (54%), concerns
as part of the assessment of appropriateness of TNF blockade
BSR guidelines for prescribing TNF- blocks in adults with AS
treatment . Because of lack of transparency and consistency,
this has been considered unsuitable for inclusion within arigorous and transparent guideline.
There are currently no longitudinal data on the preventionof ankylosis after treatment with biologicals. It is postulatedthat aggressive and persistent suppression of disease activityshould lead to prevention of structural damage. MRI is a
sensitive imaging technique that allows visualization with
Two TNF-blocking agents are presently licensed in the UK for
good anatomical detail of both the axial and peripheral skeleton.
the treatment of AS: inﬂiximab and etanercept. Others are
It is able to detect active inﬂammation, as shown by bone
likely to become available. All trials with etanercept and the
oedema, as well as chronic change. A number of studies have
majority of trials with inﬂiximab have used treatment regimens
used MRI to assess disease activity and response to treatment
as set out in the manufacturers’ recommendations. These advise
with biologicals [37–39]. Preliminary data suggest that regression
that treatment with inﬂiximab should be administered by slow
of bone marrow oedema is a sensitive sign of improvement of
intravenous infusion with a loading regimen of 5 mg/kg given
spinal inﬂammation in AS; however, all these studies reported
at weeks 0, 2 and 6, and maintenance treatment at the same
only on small numbers of patients over a period of time no
dose given at 6- to 8-weekly intervals. Etanercept is recom-
longer than 6 months. Follow-up data are sparse, and although
mended to be given by subcutaneous injection at a dose of 25 mg
preliminary results suggest a possible role for MRI as a
prognostic predictor, this needs to be conﬁrmed in larger andlonger-term studies.
Clinical efﬁcacy of TNF blockade treatment in AS
Spinal diseaseSeveral major studies, summarized in Table 1, attest to the
efﬁcacy of inﬂiximab and etanercept (in conjunction with
disease and spondyloarthropathy were treated with inﬂiximab
NSAIDs) compared with placebo in the symptomatic treatment
for resistant bowel inﬂammation. Gastrointestinal symptoms
improved and the CRP level fell. In all patients, there was
By 6–12 weeks, 70–94% of patients achieved the ASAS 20%
improvement criteria (ASAS 20) with inﬂiximab [28–31], as
did 59–78% of those treated with etanercept [32, 33]. Similarﬁndings were reported by Gorman and colleagues , though
Uveitis. A retrospective study analysed the effectiveness of
response criteria differed slightly from those recommended by
etanercept (in 14 patients) or inﬂiximab (two patients) on
the ASAS group. Davis et al.  demonstrated that around
immunosuppressive resistant eye inﬂammation when given
40% of patients achieved a 50% reduction (ASAS 50) and
either for the inﬂammatory eye disease or associated joint
around 25% achieved a 70% reduction (ASAS 70) within
disease . Eight patients had rheumatoid arthritis, three
12 weeks of etanercept treatment, with 17% classiﬁed as having
juvenile rheumatoid arthritis, one ankylosing spondylitis and
achieved ASAS partial remission after 24 weeks. Similarly,
one spondyloarthropathy. In three patients, there was no
Braun et al.  demonstrated that around 45% of patients
associated systemic disease. In all 12 patients with active
achieved an ASAS 50 response and around 20% achieved an
articular symptoms and inﬂammation, there was an improve-
ASAS partial remission at 12 weeks after three doses of
ment, but only six out of 16 patients with ocular inﬂammation
experienced improvement. Five patients developed inﬂammatory
Reduction of the BASDAI by 50% was achieved by 55% of
eye disease for the ﬁrst time whilst taking anti-TNF therapy.
patients treated with inﬂiximab  and 57% of those receiving
It was concluded that TNF inhibitors may beneﬁt certain
etanercept  within 6 weeks of treatment. Studies have
subgroups of patients with inﬂammatory eye disease, but more
also demonstrated a signiﬁcant reduction in the BASDAI
perspective studies were considered necessary.
compared with baseline values within 2 weeks of treatment withinﬂiximab [29, 35].
Currently, there are no trial data to indicate the need for, or
effects of etanercept on psoriasis and psoriatic arthritis. These
beneﬁt from, combining either agent with a second-line drug,
are cited in the BSR guideline for anti-TNF therapy in psoriatic
or to indicate the optimum duration of treatment. Response
to TNF blockade treatment occurs principally at 6–9 weeks.
Cessation of treatment with either agent usually results inrecrudescence of symptoms.
Two studies have examined the effects of anti-TNF treatmenton BMD in patients with a spondyloarthropathy. One study
used inﬂiximab, and either 5 or 3 mg/kg  demonstrated a
These guidelines refer speciﬁcally to spinal disease. Further
signiﬁcant increase in bone density at the lumbar spine, total
consideration will be given to the treatment of peripheral
hip and greater trochanter over a 6-month period. There was an
increase in the bone formation marker osteocalcin betweenbaseline and week 6 without any corresponding change in abone resorption marker. The second study examined 10 patientswith spondyloarthropathy compared with 10 controls with
shorter disease duration . Patients were treated with
These guidelines refer speciﬁcally to spinal disease. Further
etanercept 25 mg subcutaneously twice weekly. BMD at the
consideration will be given to the treatment of peripheral
lumbar spine and total hip increased in the anti-TNF group
compared with the control group treated with NSAIDs and
BSR guidelines for prescribing TNF- blocks in adults with AS
sulphasalazine, though only the total hip bone density change
There were no deaths or cases of demyelination reported.
reached statistical signiﬁcance compared with baseline.
Antinuclear antibodies developed in 42 out of 276 patients (15%)in which these data were recorded. No cases of SLE werereported.
In an open-label study of patients meeting the New Yorkcriteria for AS, inﬂiximab 5 mg/kg was infused at 0, 2 and
6 weeks . Eight of the 21 patients had MRI imagingboth before and after infusion to assess inﬂammatory change.
These guidelines have been drawn up by a working party
One patient with a contraindication to MRI was examined
whose membership and afﬁliations are recorded in Appendix 1.
with ultrasound. MRI demonstrated an improvement in seven
They have been developed for use by consultant rheumatologists
of the eight patients in the imaging cohort; improvement in
within the UK in the treatment of adults with AS. Guidelines
for the use of etanercept in children (under 19 yr of age)
In the second study, of 10 patients with spondyloarthropathy
with juvenile idiopathic arthritis have also been drawn up
treated with etanercept 25 mg twice weekly for 6 months,
(NICE Technology Appraisal Guidance 35, March 2002).
MRI scans of the sacroiliac joints, the lumbar spine and
These specialists have experience in the management of patients
affected peripheral joints were performed at baseline and
with ankylosing spondylitis and familiarity with the use of
6 months . A total of 99 entheseal lesions were detected
before treatment, of which 86% had regressed or improved at
These guidelines have been developed in the knowledge of
existing guidelines for the use of TNF-blocking drugs in patients
MRI imaging of the spine in patients with ankylosing
spondylitis before and after therapy with inﬂiximab has also
should be read in conjunction with BSR guidelines relating to
been assessed using a novel scoring system . Lesions, scored
the treatment of psoriatic arthritis, and the prevention and
by two radiologists, improved by 40% in the inﬂiximab group
management of opportunistic infections, including tuberculosis.
compared with 6% in the placebo group, determined using
These recommendations are based on available clinical
evidence. In addition to clinical trial data, the guideline group
sequences, improvement of lesions was seen in 60% of the
was cognizant of expert opinions expressed in published papers
inﬂiximab group compared with a deterioration in 21% of the
[including those listed as 51–53]. It is recognized that, as further
placebo group. The chronic lesion score improved by 7% in the
evidence becomes available, these guidelines will need to be
inﬂiximab group and worsened by 30% in the placebo group. It
was concluded that this technique, using STIR (short TI
The use of TNF-blocking drugs in this population must be
inversion recovery) and gadolinium enhancement sequences and
seen in the context of other available therapies. It is anticipated
a scoring system, is useful in assessing acute spinal inﬂammation;
that these agents will be indicated for some but not all patients,
MRI activity scores in the spine are parallel but do not precisely
and that for most patients existing modalities of treatment
will still be appropriate, either alone or in combination withTNF-blocking drugs.
Effective patient education is an important contributor to
the effective use of these guidelines.
(see Appendix 2) and have been appraised according to the
arthropathy resistant to conventional treatment at baseline,week 2 and week 12 of a conventional inﬂiximab treat-
chemically. There was a decrease in synovial layer thicknessand a reduction in the number of CD55þ synoviocytes atweek 12. Vascularity was diminished in the sublining area at
week 2, with reduced endothelial expression of VCAM, but
Eligibility for treatment with TNF-blocking drugs
not ICAM, PECAM and E-selectin. At week 12, the numbers
Treatment with TNF blocking agents may be appropriate if:
of neutrophils and CD68þ macrophages were reduced, but theoverall
The patient’s disease satisﬁes the modiﬁed New York criteria
In another study  of patients with ankylosing spondylitis,
inﬂiximab treatment down-regulated both interferon and
Radiological criterion: Sacroiliitis at least grade 2 bilaterally
TNF- secretion by T cells, but did not alter cytokine
Clinical criteria: Low back pain and stiffness for morethan 3 months that improves with exercise but is not relieved
Table 2 summarizes treatment withdrawals and adverse events
(a) Limitation of motion of the lumbar spine in both the
in clinical trials of anti-TNF- in AS undertaken to assess
treatment efﬁcacy and/or safety as the primary outcome
(b) Limitation of chest expansion relative to normal values
variables. In publications in which the same cohorts of patients
are reported, we considered this information when preparingthe table. Of 394 AS patients studied, nine (2.3%) discon-
A deﬁnite diagnosis of ankylosing spondylitis requires the
tinued treatment due to lack of efﬁcacy. Twenty-eight patients
radiological criterion and at least one clinical criterion.
(7.1%) were withdrawn because of adverse events. These
(All reasonable measures should be taken to ensure that
included three major infections (two cases of tuberculosis,
symptoms are due predominantly to AS and that alternative
causes, including spinal fracture, disc disease and ﬁbromyalgia,
patients and ﬁve systemic inﬂiximab-related infusion reactions.
BSR guidelines for prescribing TNF- blocks in adults with AS
Ankylosing spondylitis is active. Active spinal disease should be
However, the working group recommends that such a register
is set up for these patients; the BSR is currently pursuing this.
In the meantime, the BSR currently recommends that data
collection, including updated dosage, outcome and toxicity
(b) And spinal pain VAS (last week) at least 4 cm.
information, is conducted at a local level. Adverse incidents/
(c) Both on two occasions at least 4 weeks apart without any
serious side-effects arising whilst on anti-TNF therapy should
be notiﬁed immediately via the yellow card system.
Failure of conventional treatment with two or more NSAIDs,
each taken sequentially at maximum tolerated/recommendeddosage for 4 weeks.
These guidelines will be reviewed annually.
Exclusions as for rheumatoid arthritis apply. Reference should
be made to the individual drug data sheets, but importantexclusions include:
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regulation of the nonspeciﬁc and antigen-speciﬁc T cell cytokine
observational, extension study of a three month, randomised,
response in ankylosing spondylitis during treatment with inﬂiximab.
placebo-controlled trial. Arthritis Rheum 2003;48:2224–33.
31. Temekonidis TI, Alamanos Y, Nikas SN et al. Inﬂiximab therapy in
50. Ledingham J, Deighton C. Update on the British Society for
patients with ankylosing spondylitis: an open label 12 month study.
Rheumatology guidelines for prescribing TNF blockers in adults
with rheumatoid arthritis (update of previous guidelines of April
32. Brandt J, Khariouzov A, Listing J et al. Six-month results of a
2001). Rheumatology 2005;44:157–63.
double-blind, placebo-controlled trial of etanercept treatment in
51. Braun J, Sieper J, Breban M et al. Anti-tumour necrosis factor a
patients with active ankylosing spondylitis. Arthritis Rheum 2003;
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33. Davis JC, Van der Heijde D, Braun J et al. Recombinant human
52. Stokes DG, Kremer JM. Potential of tumor necrosis factor
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neutralization strategies in rheumatologic disorders other than
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34. Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing
53. Maksymowych WP, Inman RD, Gladman D et al. Spondyloarthritis
spondylitis by inhibition of tumor necrosis factor . N Engl J Med
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36. Maksymowych WP, Jhangri GS, Lambert RG et al. Inﬂiximab
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Appendix 1. Members and afﬁliations of the working group
37. Kruithof E, Van den Bosch F, Baeten D et al. Repeated infusions of
Dr Andrew Keat, Chairman (Consultant Rheumatologist,
inﬂiximab, a chimeric anti-TNFa monoclonal antibody, in patients
with active spondyloarthropathy: one year follow up. Ann Rheum
Dr Nick Barkham (Specialist Registrar in Rheumatology, Leeds
38. Marzo-Ortega H, McGonagle D, O’Connor P, Emery P. Efﬁcacy of
Dr Ashok Bhalla (Consultant Rheumatologist RNHRD, Bath)
etanercept in the treatment of the entheseal pathology in resistant
Dr Karl Gaffney (Consultant Rheumatologist, Northfolk &
spondylarthropathy: a clinical and magnetic resonance imaging study
[comment]. Arthritis Rheum 2001;44:2112–7.
Dr Helena Marzo-Ortega (Specialist Registrar in Rheumatology,
39. Brandt J, Haibel H, Sieper J, Reddig J, Braun J. Inﬂiximab
treatment of severe ankylosing spondylitis: one year follow-up.
Arthritis Rheumatism 2001;44:2936–7.
40. Brandt J, Haibel H, Reddig J, Sieper J, Braun J. Successful short
Mr Fergus Rogers (Director, National Ankylosing Spondylitis
term treatment of severe undifferentiated spondyloarthropathy
with the anti-tumour necrosis factor alpha monoclonal antibody
Margaret Somerville (Clinical Research Manager, Department
inﬂiximab. J Rheumatol 2002;29:118–22.
of Rheumatology, Northfolk & Norwich Hospital)
BSR guidelines for prescribing TNF- blocks in adults with AS
therapies (either educational or promotional) or for activities not
University of Glasgow, Consultant Rheumatologist, Glasgow
The following replies were received.
Professor Paul Wordsworth (Professor of Rheumatology,
University of Oxford, Consultant Rheumatologist, Nufﬁeld
The units in which the following working party members work
have received funding from one or more of the manufacturers oftherapies for ankylosing spondylitis: K. Gaffney, N. Barkham,H. Marzo-Ortega, R. Sturrock, M. Somerville, A. Keat.
The following working party members have received funding
Appendix 2. Process of review and appraisal of this draft
biological therapies to attend scientiﬁc meetings in the past
Formal comments have been sought by the presentation of a
24 months: N. Barkham, A. Keat, M. Somerville, F. Rogers,
draft document at the Annual Meeting of BSR in April 2004 and
BSR has established a register which is funded by the
manufacturers of biological therapies for rheumatoid arthritis;
training for rheumatologists in data collection has also been
The following working party members have received honoraria
British Society for Paediatric and Adolescent Rheumatology:
from the manufacturers of therapies for ankylosing spondylitis:
BSR Psoriatic Arthritis and TNF blockade Working Group:
The following working party members have received funding
for taking part in clinical trials of the new biological therapies:
BSR Rheumatoid Arthritis and TNF Blockade Working
No working party members declared a direct ﬁnancial stake,
such as personal shareholding, in companies manufacturing thenew biological therapies.
Appendix 3. Declaration of interest statement
The Working Party was set up independently of any input or
Appendix 4. Other guidelines and documents which should
funding from the manufacturers of the biological therapies forankylosing spondylitis.
be read in conjunction with this document
Members of the Working Party were asked to clarify their
Update of BSR guidelines for prescribing TNF- blockers
relationships with the manufacturers of the biological therapies.
in adults with rheumatoid arthritis, including update on
Members were asked to declare if they, as individuals, had been
sponsored to attend scientiﬁc or other meetings in the past
Guideline for anti-TNF- therapy in psoriatic arthritis 2004 .
24 months or if they had a direct ﬁnancial stake in the manu-
Guideline for the use of etanercept in juvenile idiopathic
facturing companies. They were also asked if their units had
arthritis (NICE Technology Appraisal Guidance 35, March
received funding from the manufacturers to take part in clinical
trials of the new biological therapies. Organizations were asked
BPRG protocol for prescribing biological therapies in children
to declare if they had received sponsorship from manufacturers
and young people with juvenile idiopathic arthritis 2000
of the new biological therapies for activities related to the new
Exam Support Controlled Assessment: The Geographical Enquiry The diversity and range of service provision is variable Introduction Your job in this enquiry will be to test the above hypothesis. Your work should include a range ofprimary and secondary data. Ideas and websites to help you with some of the key ideas and theorieson this topic are listed below. Some of the suggested sites wil
Capacity building for carbon- and biodiversity-based payments for ecosystem services in the Peruvian Amazon http://www.geog.leeds.ac.uk/projects/espa/ Tim Baker, Olivia Rendon, Ivis Chan (University of Leeds, UK); Dennis del Castillo, Eurídice Honorio (Instituto de Investigaciones de la Amazonia Peruana, Peru); Cesar Moran Cahusac (Amazon Conservation Association, Peru); Jul