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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2004 Apr;63(4):426–430. doi: 10.1136/ard.2003.010967

Dose escalation of infliximab in clinical practice: improvements seen may be explained by a regression-like effect

R F van Vollenhoven 1, S Brannemark 1, L Klareskog 1
PMCID: PMC1754945  PMID: 15020338

Abstract

Objective: To determine whether increased infliximab doses result in better clinical outcome in rheumatic diseases.

Methods: Subjects were 124 patients with rheumatoid arthritis treated with biological agents at a single institute. Index cases were 44 patients whose infliximab doses had been increased. Controls were patients treated with infliximab without dose increase (n = 44), and patients treated with etanercept (n = 36). Disease activity score (DAS28), ACR28 swollen joint counts, and numerical ACR responses were compared before and after dose increases. For the controls, the point at which the DAS28 value showed any increase (despite infliximab/etanercept treatment) was used as the reference time point. Comparisons were made between three sets of outcomes: best outcome achieved before the dose increase (cases) or before the reference time point (controls); outcomes at this point; and best outcomes after this point.

Results: Following dose increase, disease activity showed modest but statistically significant improvements. The improvement achieved after dosage escalation was equal to, but not better than, the best values before dose escalation. While this finding could be interpreted as "recapturing" the previous response, similar improvements were seen in both control groups. Thus the same pattern of worsening and subsequent improvement was seen with or without the infliximab dose increase.

Conclusions: Clinical improvement with increased infliximab dose, and the impression that a previous response can be "recaptured" with higher doses, cannot be taken at face value, as similar improvements occurred in two control groups. The use of infliximab at doses higher than 3 mg/kg needs to be evaluated further.

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Figure 1 .

Figure 1

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Infliximab dose escalation. DAS28 values (A) and 28 swollen joint counts (B) at the last visit before dose escalation, at the first visit following dose escalation, and the best result after dose escalation. Box plots show median values and 25–75% interquartile range. Statistical comparisons are by paired Student t test. ACR28, American College of Rheumatology 28 joint score; DAS28, 28 joint count based disease activity score; SJC, swollen joint count.

Figure 2 .

Figure 2

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Comparisons of DAS28 (left panel), ACR28 swollen joint count (middle panel), and ACR-N (right panel) before and after dose escalation. Shown are, from left to right in each panel: the best value at any time point before the dose increase; the values at the time of the last visit before the dose increase; the values at the first visit after the dose increase; and the best values at any time point after dose increase. The results clearly show that the best result after dose escalation is similar to the best result before dose escalation. Error bars = SEM. ACR28, American College of Rheumatology 28 joint score; ACR-N, numeric ACR score; DAS28, 28 joint count based disease activity score; SJC, swollen joint count.

Figure 3 .

Figure 3

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Case–control study: graphs showing DAS28 (A), ACR28 swollen joint counts (B), and ACR-N (C) for cases (patients whose infliximab dosages were increased: solid lines), infliximab controls (whose dosages were not increased: dashed lines), and etanercept controls (dotted lines). The values plotted are the best results before dose escalation (for the cases) or before the reference time point (for the controls); the values at the last visit before these time points; and the best values thereafter. Error bars = SEM. ACR28, American College of Rheumatology 28 joint score; ACR-N, numeric ACR score; DAS28, 28 joint count based disease activity score; SJC, swollen joint count.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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