VIENNA, Austria-Two new studies presented here examined the efficacy and cost-effectiveness of low-dose regimens of infliximab for ankylosing spondylitis (AS).1,2 The current standard of care for AS being studied in clinical trials at present is 5 mg/kg every 6 weeks; however, these smaller observational studies both assessed the efficacy of the dose typically used in rheumatoid arthritis (RA), 6 mg/kg every 8 weeks, following an induction course at 0, 2, and 6 weeks.

"In our experience, the low dose is as effective as the higher dose," Ramesh Jois, MD, department of rheumatology at Norfolk and Norwich University Hospital in Norwich, UK, tells CIAOMed. "Of the 13 patients whom we have tried on the low dose, only one has gone to the higher dose," he notes. Among the remaining 12 patients, the average BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score at 3 months improved to 3.03 from a baseline of 6.17.

"We only go to the higher dose if patients are not responding to the low dose, and eight of these patients have now completed a year, and they're still on low-dose infliximab, so we think it works," Dr. Jois says.

Another observational study that examined the effects of the same regimen did not find similar efficacy results. Of 16 patients initiated on low-dose infliximab, one half showed a 50% BASDAI improvement. To achieve this response, however, the frequency and/or dose of infliximab were increased in 11 patients. "Nevertheless," the authors conclude, "this study suggests the possibility to adapt the dose of infliximab for each patient according to the clinical response."

 

Low dose infliximab appears cost-effective

Given its efficacy, the cost-effectiveness of this regimen appears significant, Dr. Jois suggests. "If you're looking at just the direct drug costs, leaving out the patient coming into the hospital for a 2-hour stay, you're looking at a savings of about £15,000 (US$27,187) per patient per year," he points out. "Of the 12 patients that we treated on the low dose, it totaled about £165,000 (US$299,062) in our unit for that whole year." Dr. Jois and his colleagues advise that all AS patients be started on low-dose infliximab and that increasing to the higher, licensed dose be considered only if patients fail to respond.

 

Initial rituximab efficacy results suggest improved outcomes at week 52

While there is considerable experience with the use of the humanized anti-TNF-α antibody adalimumab in the treatment of RA, relatively little data exist about its use in AS. A poster presented here on Friday details the 52-week results of an initial efficacy trial in 15 patients.3

Adalimumab 40 mg was administered subcutaneously every other week to patients with active AS. Reported clinical outcomes included assessments of disease activity, function, pain, enthesitis, quality of life, and C-reactive protein (CRP). The primary endpoint of the study was improvement of disease activity at week 12, as measured by attainment of BASDAI50.

Week 52 data indicate that 87%, 60%, and 47% achieved BASDAI20, -50, and -70 outcomes relative to baseline. This represents an improvement over disease activity assessments at week 12, in which only 16% of patients achieved BASDAI70. Significant improvements were also reported in all clinical measures, and a clear, but not significant, improvement of acute inflammatory lesions as detected by serial MRI was demonstrated.

"Compared to the other TNF-α inhibitors, these results are quite similar," Hildrun Haibel, MD, researcher at the Charité University Hospital in Berlin, Germany, tells CIAOMed. "We had very few side effects and no serious infections," she adds. "There are two Phase III trials underway, which include 400 to 500 patients, and the placebo controlled data from these trials will be presented at ACR."

 

Clinical response to discontinuation

Currently, in its use for AS, infliximab is administered every 6 weeks, indefinitely. A study presented here by Xenofon Baraliakos, MD, researcher at Rheumazentrum Ruhrgebiet in Herne, Germany, and his colleagues sought to test the effects of discontinuing infliximab therapy in AS patients.4

The study followed 42 patients who discontinued therapy after 3 years. They were visited regularly to assess clinical relapse, which was defined as an increase of the BASDAI and physician's global assessment indices >4. Patients meeting this criterion were reinfused with infliximab on the same dosing schedule (5mg/kg every 6 weeks) and reassessed over the course of 1 year. The primary outcome of the study was disease activity 1 year after readministration of infliximab compared to the times of discontinuation and relapse.

Although one of the original 42 patients is in ongoing remission without anti-TNF therapy, the remaining 41 were restarted on infliximab therapy due to clinical relapse, which occurred after a mean of 17.5 weeks (range 7-45 weeks). Because of one drop-out, 40 patients completed 1 year of treatment following relapse.

The mean BASDAI scores at discontinuation, relapse, and at the end of 1 year of readministration were 2.5 (SD 1.8), 6.0 (1.4), and 2.6 (1.9), respectively. Other clinical measures, including functional index, metric index, patient and physician global assessment, and CRP showed similar responses to retreatment. So, although discontinuation of therapy resulted in relapse, readministration of infliximab in these patients appears effective.

One concern of intermittent dosing, however, is the increased possibility for the formation of antitherapeutic antibodies. The authors indicate that testing of serum samples from this population for the presence of anti-infliximab antibodies is underway.

References:

1. Jois RN, Leeder J, Gibb A, Gaffney K, Merry P, Scott DGI. Low-dose infliximab for ankylosing spondylitis in clinical practice - more cost effective? Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract FRI0213.
2. Zarnitsky C, Pouchat J, Chopin B, et al. Treatment by infliximab with lower doses of three mg per kg every eight weeks in ankylosing spondylitis (AS): a prospective observational cohort analysis of efficacy. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract AB0215.
3. Haibel H, Brandt H, Baraliakos X, et al. Adalimumab in the treatment of active ankylosing spondylitis: results of an open-label, 52-week trial. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract FRI0200.
4. Baraliakos X, Listing J, Brandt J, et al. Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab - results of a follow-up after one year of readministration. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract FRI0222.