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Treatment of ankylosing spondylitis with infliximab
  1. C A BOEGER,
  2. H WITTWER,
  3. M SCHATTENKIRCHNER,
  4. H KELLNER
  1. Rheumatology Unit
  2. Medizinische Poliklinik, Munich, Germany
  3. Radiological Institute
  4. Munich University Hospital, Germany
  1. carsten.boeger{at}gmx.net
  1. W KELLNER
  1. Rheumatology Unit
  2. Medizinische Poliklinik, Munich, Germany
  3. Radiological Institute
  4. Munich University Hospital, Germany
  1. carsten.boeger{at}gmx.net

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In January 2000 a 35 year old man presented with severe ankylosing spondylitis (AS), diagnosed in 1981. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 6.0, the Bath Ankylosing Spondylitis Functional Index (BASFI) was 3.0, and on a 1–10 visual analogue scale (VAS) for pain in the previous two months he had a score of 6.

Schober's test was 0 cm (normal 4 cm), Ott's test 1 cm (normal 2 cm), finger-floor distance 16 cm, lateral flexion 3 cm, tragus-wall distance 21 cm, cervical rotation 30°.

C reactive protein (CRP) was 41 mg/l (normal <5), erythrocyte sedimentation rate (ESR) was 25 mm/1st h (normal <15), and HLA-B27 genotype was positive.

Conventional radiography showed typical signs of AS. Magnetic resonance imaging (MRI) detected inflammatory activity in the ileosacral joints1 by contrast enhancement after gadolinium application in the apical portion of the right ileosacral joint in T1 weighted sequences (fig 1).

Figure 1

Gadolinium contrast enhanced T1 weighted magnetic resonance imaging before treatment with infliximab (A) showing contrast enhancement in the right ileosacral joint, and (B) in week 41 of treatment showing no contrast agent uptake.

We started treatment with infliximab,2 a monoclonal antibody (IgG1) directed against tumour necrosis factor α (TNFα), at a dose of 5 mg/kg body weight. Intravenous infusions were given in weeks 0, 2, 6, and then continued at six weekly intervals for one year without any additional disease modifying drug.

Pain improved within 24 hours of the first infusion. Within six weeks the patient required no ibuprofen and CRP, ESR, BASDAI, BASFI, and VAS improved dramatically (fig 2). With the exception of CRP and ESR, all variables remain normal up to now. CRP and ESR increased mildly at week 12 owing to a mild upper respiratory tract infection. There were no other adverse events. Two mobility variables (cervical rotation and tragus-wall distance) had improved at the end of one year's treatment.

Figure 2

Self assessment of pain on a 1–10 visual analogue scale (A) and CRP and ESR (B).  

MRI of the ileosacral joints showed no contrast enhancement at weeks 14 and 41 of treatment (fig 1).

The patient denied any loss of effect at the end of the six weekly infusion intervals or after one year of treatment. Except for the mild upper respiratory tract infection, which abated after two weeks without specific treatment, there were no adverse events.

This case report documents the first long term application of infliximab in a patient with AS. Two previous studies reported effective treatment of a total of 22 patients with AS with three infusions of infliximab at a dose of 5 mg/kg body weight.3 4

The pharmacological basis for TNFα inhibitory treatment in AS is the detection of TNFα-mRNA and TNFα protein in biopsy specimens of ileosacral joints of patients with active AS.5 In rheumatoid arthritis (RA) and Crohn's disease (CD), several TNFα inhibitors seem to be successful in significantly reducing inflammatory activity.6 7

Theoretically, up regulation of the TNFα receptors and subsequent tachyphylaxis might be expected upon constant blockade of the agonist. This has not been noted in studies on infliximab, etanercept, and D2E7 in RA, CD, and psoriatic arthritis (PA) during long term treatment, even when constant therapeutic plasma levels are maintained.7-9 This case report suggests this is true also for patients with AS.

In summary, we present the case of a patient with AS effectively and safely treated with infliximab over a period of more than one year. This indicates that treatment of AS with TNFα inhibiting substances may have equal long term safety and long term benefits on peripheral and spinal joint function as does treatment of RA, CD, and PA. Randomised controlled double blind studies are needed to investigate this in further detail.

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