Veale_edit.qxp 1/10/07 12:19 Page 22
Spondyloarthropathies
clinical practice, based on the literature and experience in RA and compared with MTX or SZP.
28,29
The main limitation is CyA-related
psoriasis patients,
18
higher MTX dosages (up to 25mg/week) appear to toxicity, including hypertension and renal damage.
be beneficial in peripheral arthritis,
9
but not in axial disease.
7
In partial
responders, association of MTX and cyclosporine-A (CyA) has also Only limited data are available regarding joint damage prevention
been shown to be effective.
19
However, liver toxicity is a concern with achieved by DMARDs. A retrospective open-label study of 38 patients
MTX use for PsA. In a meta-analysis of 636 PsA and RA patients on failed to show any benefit of MTX compared with placebo.
30
In
long-term MTX medication, the incidence of progressive liver disease addition, no significant difference regarding radiological progression
was identified for combination of CyA and MTX compared with MTX
alone, although the study was probably underpowered to demonstrate
a difference.
19
In a small open-label study, SZP also failed to prevent
Mesalazine may be an alternative for radiological progression.
31
patients who are non-tolerant to
Anti-tumour Necrosis Factor α Agents
sulfasalazine, and may also be effective
Improvements in our understanding of the mechanisms underlying
for the treatment of associated colitis.
chronic autoimmune disease have led to the development of targeted
treatment. A therapy that blocks the TNFα pathway – a key pro-
inflammatory cytokine – has revolutionised the management of PsA
and psoriasis. Currently, three anti-TNFα agents (aTNFα) are available:
was 27.9%, and was more frequent among psoriasis patients.
20
The etanercept, infliximab and adalimumab.
rate of liver disease progression was associated with cumulative
MTX dosage. There is no consensus regarding indication of liver Etanercept (Enbrel™) is a soluble TNFα receptor fusion protein
biopsy, and recommendations vary greatly between rheumatologists delivered by subcutaneous injection of 50mg once weekly. Its approval
and dermatologists.
2
for management of PsA was based on two placebo-controlled studies.
The first was a three-month placebo-controlled trial followed by a six-
Sulfasalazine (SZP) has been more widely studied. The largest trial
was a 36-week placebo-controlled study in 221 active PsA patients.
21
In
the SZP group, 57.8% of patients achieved the Psoriatic Arthritis
Response Criteria (PsARC) end-point compared with 44.6% in the
The Infliximab Multinational
placebo group. Nevertheless, SZP has shown effectiveness only on
Psoriatic Arthritis Controlled
peripheral joint disease;
22
efficacy on the rash seemed more marginal. In
most of the SZP studies, the drop-out rate was high (26–44%), which is
Trial (IMPACT) has established
related to lack of efficacy and adverse skin or gastrointestinal reactions.
2
the efficacy of infliximab for
Mesalazine may be an alternative for patients who are non-tolerant to
SZP,
10
and may also be effective for the treatment of associated colitis.
23
psoriatic arthritis patients.
One hundred and ninety PsA and psoriasis patients were included in a
large multinational, double-blind trial comparing leflunomide with month open-label study including 60 patients with active PsA, defined
placebo.
24
Statistically more patients achieved PsARC criteria in the as at least three swollen and three tender joints.
32
Eighty-seven per
leflunomide group. Leflunomide was also superior in terms of joint cent of the patients in the etanercept arm achieved the primary end-
tenderness and swelling score, Dermatology Life Quality Index (DLQI) point – at least 30% improvement in tender or swollen joint count and
total score and Health Assessment Questionnaire (HAQ). A subsequent improvement of patient’s or physician’s global assessment – compared
analysis in these patients showed leflunomide to be effective on the with 23% in the placebo arm (p<0.0001). American College of
skin disease as well.
25
Rheumatology (ACR) criteria 20, 50 and 70 were met by 73, 50 and
13%, respectively, of the patients on etanercept treatment compared
with 13, 3 and 0%, respectively, in the placebo group. Function
assessed using HAQ and skin disease evaluated by the Psoriasis Area
Improvements in our understanding of
and Severity Index (PASI) score also showed significant improvement
the mechanisms underlying chronic
following treatment. A second multicentre study was conducted on
205 patients.
33
It confirmed the results of the first trial and, for the first
autoimmune disease have led to the
time, showed inhibition of radiological progression in PsA. The benefit
development of targeted treatment.
of etanercept was maintained at two years.
34
Dose escalation to 50mg
twice weekly may improve skin management, although this has not
been shown to provide added benefit for the joint disease.
35
Placebo-controlled RCTs have attested to the efficacy of CyA in both Infliximab (Remicade™) is a chimeric monoclonal antibody
the induction and maintenance of remission in psoriasis,
26,27
but no administered intravenously every six to eight weeks. In 21 active
placebo-controlled studies have evaluated CyA for the management of spondyloarthropathy patients, including nine with PsA, Van den Bosch
PsA. However, CyA appeared to be an effective treatment for PsA et al. evaluated the safety and efficacy of three infliximab infusions.
36
22 EUROPEAN MUSCULOSKELETAL REVIEW 2007
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