Tumor-necrosis factor-alpha (TNF-a) blockers etanercept (Enbrel) and infliximab (Remicade) are becoming increasingly popular in the treatment of various forms of spondylitis. However, not all patients respond to the TNF-a blockers, and some who do respond develop side effects that limit treatment. In such situations, doctors and patients question whether it is worth prescribing the other TNF-a blocker or whether it is a waste of time and money. Alternatives are few in spondylitis and both the doctor and patient may be motivated to “try anything”; yet it is important to avoid a therapeutic trial of a medication that has no likelihood of being effective in view of the risks that exist with TNF-a blockers and their cost.

As the number of treatment options in spondylitis steadily increases, doctors in the not too distant future may have to weigh the potential benefit of a second TNF-a blocker with other biological and pharmacological treatment options.

Therefore, researcher R. van Vollenhoven and colleagues from the Karolinska Hospital in Stockholm, Sweden, investigated patients that experienced failure in treatment of one TNF-a blocker (etanercept or infliximab) to determine whether it makes sense to treat them with the other TNF-a blocker.

Study Logistics
Thirty-one patients at the Karolinska Hospital, who had received both etanercept and infliximab, were followed since 1999. Their STURE database collects efficacy (power to produce the desired effect) and safety data for all patients starting biological treatments at the major hospital in Stockholm.

Previous to this study, 18 of the 31 participants had received etanercept first; discontinuation was mostly due to lack of efficacy. Fourteen of the 18 patients had rheumatoid arthritis (RA) and 13 were seropositive, two had a diagnosis of juvenile chronic arthritis but were now adults with an RA-like clinical course, and two had spondylitis (seronegative) with predominant peripheral joint involvement. They had received etanercept for a mean of 6.8 months before switching to infliximab.

Previous to the study, 13 of the 31 participants had received infliximab first; discontinuation was mostly due to adverse events (infusions reaction, liver toxicity, change in the sense of smell, or unspecified). Eleven of these patients had RA and nine were seropositive, one was diagnosed with juvenile chronic arthritis, and one had spondylitis. They received infliximab and methotrexate (a drug oftentimes prescribed in concordance with infliximab in people with RA and sometimes in people with spondylitis) for a mean of 5.5 months before discontinuation.

Etanercept was always given by infection at 25mg twice weekly. Infliximab was given intravenously at 3mg/kg at week 0, 2 and 6, and every 8 weeks thereafter.

Participants were evaluated by a disease activity score at the study’s start and at months three, six and twelve, and annually thereafter.

Results
Researchers found that infliximab provided better results in those who did experience improvement from etanercept. They suggest that a trial of infliximab is reasonable for these patients.

Similarly, for patients who discontinued infliximab based on adverse events, treatment with etanercept gave at least similar clinical improvement, and some received better results than seen with infliximab. The adverse events that led to discontinuation of infliximab all resolved and did not recur during treatment with etanercept. When treatment was switched to etanercept, methotrexate was continued in eight and discontinued in five patients.

Taken together, the data provides support for a trial of the other TNF-a blocker in patients when one TNF-a blocker has failed.

“Thus, it would be more correct to state when etanercept fails with or without methotrexate, infliximab with methotrexate can give a significantly higher number of responders,” explained the study’s researchers.

Things to Keep in Mind
The authors point out that these results should be interpreted with caution due to a small number of study participants, differences in the studied diseases and differences in the concurrent use of methotrexate.

Moreover, because the reasons for discontinuing the first TNF-a blocker were not the same between the two groups, this study does not allow for a direct comparison between the two groups of participants or between the effectiveness of the second TNF-a blocker in each situation.