BOSTON, Massachusetts—Infliximab (Remicade®, Centocor Inc) studies reported at the 2007 American College of Rheumatology offered suggestions on how to cut infusion time, how to predict who will respond, and what to expect when treating ankylosing spondylitis (AS) patients.

How to shorten infusion time

Eileen Shinners et al from Our Lady's Hospice in Dublin, Ireland, described their protocol for safely reducing infliximab administration time from 2 hours to 30 minutes [Table 1]. They use 2-hour infusions for the initial five doses, then 1-hour infusions for the next five, and 30-minute infusions thereafter.¹ "Greatest care is taken during the first five infusions. Infusions [of six or more] can be given at a faster rate provided no adverse events are observed during the first five infusions," Dr. Shinners explained.

Fully 98 patients have been switched from the old regimen to the reduced infusion rate and 23 newly-prescribed patients have been treated according to this protocol, with only one case of severe bronchospasm reported to date in >918 infusions.

Some infliximab dosage adjustment may be needed beyond first 6 months of treatment

Watson et al tracked dosage changes of rheumatoid arthritis (RA) patients using 5 years of data from the US Medicare program and found that the period required for titration may be slightly longer than previously thought.² They found that after the first 2 quarters of treatment, there was a steady decrease in the proportion of patients needing dosage changes. From quarters 11 through 19, <15% of patients needed dosage changes in a single quarter, which implies that long-term patients treated with infliximab changed dose less than once a year.

"For RA sufferers who are tolerating infliximab, it appears there may be a slightly longer effective titration period than previously thought. Rather than just being titrated in the first 2 quarters of treatment, there is some continual gradual titration occurring until a point at which changes in dosage become infrequent and smaller. The implication is that the initial titration period of <6 months may not be sufficient; patients are effectively titrated over a longer period before they reach a stable treatment dose. This may mean that practitioners should not find it unusual to continue to have changes in dosage, but the frequency of changes in dosage should be declining over time," Dr. Watson said.

Using synovial biopsy analysis predicts who will respond

A Dutch research team led by Tineke T. van der Pouw Krann, Sr, MD, showed that microanalysis of synovial gene expression can be used to predict which patients will respond to infliximab.³ Patients who responded to infliximab therapy had upregulated expression of genes involved in immunity and defense; cell surface receptor-mediated signal transduction; cell adhesion; cytokine- and chemokine-mediated signaling pathways; cell-adhesion-mediated signaling; and signal transduction. The microarrays measure expression of about 20,000 unique genes.


Early and late, infliximab is effective in AS—perhaps even at a lower dose

A number of studies of infliximab in AS were reported.

• Barkham et al reported that in HLA-B27 positive patients with inflammatory back pain and positive MRI (90% of whom would be expected to progress to AS), infliximab was significantly better than placebo at providing a rapid reduction in disease activity on MRI and measures of clinical efficacy. The researchers concluded, "This is the first therapy to show suppression of the inflammatory lesions on MRI in very early ankylosing spondylitis."⁴
• Braun et al found that the reduction in MRI-detected spinal inflammation detected at week 24 of AS treatment was sustained over 2 years.⁵
• Canadian researchers led by Walter P. Maksymowych, MD, suggested that the beneficial effects of infliximab in AS might be attainable at a dose of 3 mg/kg (the dose typically recommended for RA) rather than the 5 mg/kg dose used in most studies.⁶ "Treatment with low-dose infliximab leads to a large treatment effect on spinal inflammation scored by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI method," they concluded.
• Cheung et al reported that infliximab is effective even in patients with severe active AS and spinal ankylosis.⁷
• Although the patients with spinal ankylosis were less likely to achieve partial remission, the proportion in full-time employment rose from 45% at baseline to 82% after 54 weeks of treatment, compared with an increase from 33% to 73% in AS patients without spinal ankylosis. "In real life clinical practice, patients with established disease with spinal ankylosis and high levels of inflammation and disease activity can achieve a major clinical response with infliximab," Dr. Cheung said.

Table 1: Protocol for Reducing Infliximab Infusion Time

No. of Infusions	Infusion Duration (h)	Monitoring Schedule (per h)	Post-infusion Monitoring (per h)
1-5	2	0.5 TPR, BP	0.5 TPR, BP for 2 h
6-10	1	0.5 TPR, BP	0.5 TPR, BP for 1 h
>10	0.5	TPR pre-, post-infusion	TPR, BP 0.5 post-infusion

TPR = temperature, pulse, respiration; BP = blood pressure

Adapted from Shinners et al. American College of Rheumatology Meeting, 2007.¹


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