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An open-label study of zoledronic acid (Aclasta 5 mg iv) in the treatment of ankylosing spondylitis
  1. G P R Clunie1,
  2. A Ginawi1,
  3. P O'Conner2,
  4. P W Bearcroft3,
  5. S J Garber4,
  6. S Bhagat1,
  7. A Grainger2,
  8. J S H Gaston5
  1. 1 Department of Rheumatology, Addenbrooke's Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK
  2. 2 NIHR Leeds Biomedical Medical Research Unit, Chapel Allerton Hospital, Leeds Teaching Hospitals Trust, Leeds, UK
  3. 3 Department of Diagnostic Imaging, Addenbrooke's Hospital, Cambridge University NHS Foundation Trust, Cambridge, UK
  4. 4 Department of Radiology, The Ipswich Hospital NHS Trust, Ipswich, UK
  5. 5 Department of Medicine, Cambridge University School of Medicine, Addenbrookes Hospital, Cambridge, UK
  1. Correspondence to Dr GPR Clunie, Department of Rheumatology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; gavin.clunie{at}doctors.org.uk

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Spinal lesions in ankylosing spondylitis (AS) include osteitis and spondylodiscitis—bone lesions characterised by high signal on T2w fat-suppressed or STIR magnetic resonance (MR) imaging.1 Pamidronate treats osteitis and improves spinal symptoms in non-steroidal anti-inflammatory drug (NSAID)-refractory AS,2 but treatment gains are modest. Zoledronic acid (Aclasta/Reclast; ZA) is more ‘potent’ than pamidronate,3 but it is unknown whether ZA improves osteitis in AS. We evaluated whether ZA reduces osteitis lesions in AS using an MR index of spinal osteitis4 previously shown to correlate with, and be responsive to treatment of, AS disease activity measures.5

Patients with AS (modified New York criteria,6 >18 years old, Bath AS Disease Activity Index (BASDAI) ≥4.15, anti-tumour necrosis factor α (anti-TNFα)-naive) were recruited based on having osteitis in two or more discovertebral units (DVUs; SPARCC definition on fat-suppressed MR images),4 as determined by a local radiologist (SJG or PWB). Eligible patients received intravenous ZA 5 mg following local site guidelines. Ethics and MHRA (2007-000087-25) approval was obtained. MR images from pre-treatment and 3 and 6 months after treatment were anonymised, coded and then scored by two radiologists (PO'C and AG) experienced in SPARCC scoring, blind to the timing of scans and each others’ scores. Scoring was done on the most abnormal six DVUs on three contiguous sagittal slices of STIR images. An average of the two scorer's total scores for each study was taken.

Clinical data were obtained pre-treatment and 3 and 6 months after ZA (NSAID use chart, spinal pain index (VAS), BASDAI, Bath AS Functional Index (BASFI) and Maastricht AS Enthesitis Score (MASES)).7

Of 11 patients recruited, 7 (6 male/1 female; age range 35–54 years) qualified for ZA treatment (four patients not having ≥2 scorable DVUs on initial MR). No patients were taking immunosuppressants (table 1).

Table 1

Details of the seven AS patients treated with zoledronic acid: baseline data

Baseline SPARCC scores ranged between 16–66/108. SPARCC sores improved in 4/7 patients by 3 months after treatment (3/4 by at least five points—the minimally important change (MIC),8 all sustained improvement through 6 months). At 6 months, 6/7 patients had improved SPARCC scores compared with baseline (by 19–76% with 4/7 patients by at least the MIC with another two improving by 4 and 4.5 points). The MR observers’ scores were identical for 79% of DVUs, differing in 21% by a maximum of one only (table 2).

Table 2

SPARCC scores in seven patients treated with zoledronic acid

BASDAI improved from 6.3 to 5.1 at 6 months (mean BASFI from 6.0 improving to 5.5 at 3 months and to 4.1 at 6 months). Mean pre-treatment MASES was 5.1, improving to 3.9 at 6 months. Median spinal pain (VAS) improved by 55% at 3 months (range 28–63%) sustained in 4/7 patients at 6 months.

To our knowledge this is the first report of the effect of ZA on osteitis in AS. ZA may reduce spinal osteitis in AS and may be associated with improvement in spinal symptoms for up to 6 months. Further controlled studies are required to evaluate clinical improvement in milder AS and axial spondylarthropathy; whether ZA-associated osteitis treatment can affect syndesmophyte formation and whether ZA has a role as adjunctive therapy in patients treated with anti-TNFα.

Acknowledgments

Dr Bearcroft is supported with research funding from the National Institute for Health Research Cambridge Biomedical Research Centre.

References

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Footnotes

  • Contributors GPRC devised the study, wrote protocol, made submissions to ethics and MHRA and was acting CI. He wrote the paper with AG. He submitted to the journal. JSHG was official CI. PO'C and AG reported the MRIs. PWB and SJG were local radiologists reporting baseline scans for recruitment purposes. SB and AG helped recruit patients and run (as consecutive PIs) the study at one centre.

  • Funding The study was made possible by an unrestricted grant awarded to Dr Clunie by Novartis. Novartis had no part in the study design or the collection, analysis or interpretation of the data nor in the writing of the report or in the decision to submit the paper for publication.

  • Competing interests None.

  • Ethics approval Cambridgeshire 4 Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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