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A recent paper described a randomised comparative study of intravenous (IV) pulse methylprednisolone versus infliximab treatment in patients for whom methotrexate treatment had failed.1 The conclusions that infliximab treatment offered substantial benefits over IV methylprednisolone may be correct, but the design of the trial has resulted in a biased assessment in favour of IV infliximab treatment. In addition, the failure of the IV methylprednisolone treatment to alter significantly a number of clinical and laboratory measures, including serum C reactive protein levels, is at odds with published reports.2–7
A comparison between the patient group in that study1 and our previous papers on the use of IV methylprednisolone treatment2,3,6 suggests that the patients in each study had similar disease duration, seropositivity, and clinical and laboratory measures of disease activity. Two main differences between the two patient groups are the background corticosteroid use (none in our study and most patients in the study by Durez et al) and the use of methotrexate. It has been our anecdotal experience that patients receiving long term oral corticosteroids do not respond as well, or for as long, to IV methylprednisolone as do patients who are not receiving oral corticosteroids and may require more frequent administrations of IV methylprednisolone for the same effect. However, I am not aware of any published data to support this. Whether this might explain the lack of response to IV methylprednisolone in the study by Durez et al is unclear.
In addition, the comparison between a single dose of IV methylprednisolone and three infliximab infusions, while reflecting the authors’ usual clinical practice, is certainly a comparison biased in favour of the infliximab treated patient group. It should be remembered that there are no published data to validate the requirement for infliximab infusions at 0, 2, and 6 weeks. Some evidence suggests that a more sustained response to daily infusions of 1000 mg methylprednisolone succinate for 3 days rather than a single IV infusion is preferable, and our own studies showed a mean duration of response of only 5.1 weeks, suggesting that repeated infusions with IV methylprednisolone might have resulted in more benefit from this treatment. It might have been better for the authors to compare either consecutive daily infusions for 3 days or monthly infusions of IV methylprednisolone, especially as the main outcome measures were at week 14 after treatment.
We thank Dr Smith for his comments on our study,1 which were largely addressed by Buttgereit et al.2 As already answered, the lack of significant response to intravenous methylprednisolone in our group of patients with rheumatoid arthritis (RA) is probably related to their disease severity, reflected by their previous treatments.
As an alternative hypothesis, suggested by Dr Smith, we can also speculate that our patients belong to a corticosteroid resistant RA subset. The mechanisms of resistance to steroids are unknown in RA but have recently been explored in patients with asthma.3
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