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Review
. 2011 May 25;13 Suppl 1(Suppl 1):S2.
doi: 10.1186/1478-6354-13-S1-S2.

Infliximab: 12 years of experience

Josef S Smolen  1 , Paul Emery
Affiliations
Review

Infliximab: 12 years of experience

Josef S Smolen et al. Arthritis Res Ther. .

Abstract

Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are immune-mediated conditions that share an inflammatory mechanism fuelled by excessive cytokines, particularly TNF. Control of inflammation and rapid suppression of cytokines are important in treating these diseases. With this understanding and the corresponding advent of TNF inhibitors, RA patients, AS patients and PsA patients have found more choices than ever before and have greater hope of sustained relief. As a widely used TNF inhibitor, infliximab has a deep and established record of efficacy and safety data. Extensive evidence - from randomised controlled clinical trials, large registries and postmarketing surveillance studies - shows that infliximab effectively treats the signs and symptoms, provides rapid and prolonged suppression of inflammation, prevents radiologically observable disease progression and offers an acceptable safety profile in RA, AS and PsA. In very recent studies, investigators have observed drug-free remission in some patients. Additionally, infliximab may interfere with rapidly progressing disease in RA by early addition to methotrexate in patients with signs of an aggressive course. Finally, infliximab has been shown to reduce PsA clinical manifestations such as nail involvement. With our current understanding, substantial data and increasing confidence regarding use in practice, infliximab can be considered a well-known drug in our continued campaign against inflammatory rheumatic diseases.

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Figures

Figure 1
Figure 1
Early rheumatoid arthritis: radiological progression. Infliximab plus methotrexate (MTX) reduces progression of joint damage in rheumatoid arthritis compared with MTX alone (P < 0.001 at weeks 30 and 54) [45]. vdH-S, van der Heijde–Sharp.
Figure 2
Figure 2
Early rheumatoid arthritis: disease activity. Changes in total Sharp score (TSS) by disease activity states, as classified by the simplified disease activity index. IFX, infliximab; MTX, methotrexate; NS, not significant. Modified from [51].
Figure 3
Figure 3
Rapidly progressing disease in rheumatoid arthritis. Matrix risk model for the probability of rapid radiographic progression (RRP) in 1 year, including all selected baseline risk factors, except (a) erythrocyte sedimentation rate (ESR) or (b) C-reactive protein (CRP), generated from the ASPIRE early rheumatoid arthritis dataset. Numbers in each cell represent the percentage (95% confidence interval) of patients who had RRP out of all patients who have the baseline characteristics and receive the initiated treatment as indicated. Predicted probability of RRP: blue, 0 to 9%; green, 10 to 19%; yellow, 20 to 29%; orange, 30 to 39%; red, 40 to 100%. A higher percentage indicates more severe radiographic progression of joint damage. IFX, infliximab; mono, monotherapy; MTX, methotrexate; RF, rheumatoid factor; SJC, swollen joint count. Reprinted with permission from [47].
Figure 4
Figure 4
Established rheumatoid arthritis: progression of structural joint damage. Infliximab (IFX) plus methotrexate (MTX) significantly reduces progression of structural joint damage compared with MTX alone, after 1 year of treatment. All patients received concomitant MTX [32]. P < 0.001 for all doses and courses. vdH-S, van der Heijde–Sharp.
Figure 5
Figure 5
Established rheumatoid arthritis: inflammation and joint destruction. Mean change from baseline to week 54 in modified van der Heijde–Sharp score among patients who remained clinical nonresponders from week 2 through week 54, by treatment group. Corresponding median changes in the methotrexate (MTX)-plus-placebo-treated group (placebo) and the groups receiving infliximab (IFX) 3 mg/kg every 8 weeks plus MTX, IFX 3 mg/kg every 4 weeks plus MTX, IFX 10 mg/kg every 8 weeks plus MTX, and IFX 10 mg/kg every 4 weeks plus MTX, as well as all IFX-plus-MTX groups were 3.50, 0.27, –0.50, –0.25, 1.25 and 0.00, respectively. *P <0.05, **P <0.01 versus MTX-plus-placebo-treated patients. Dosage and frequency data (4 weeks, 8 weeks) refer to infliximab treatment. Modified with permission from [33].
Figure 6
Figure 6
Ankylosing spondylitis: disease activity. Infliximab rapidly reduces disease activity compared with placebo (n = 70 patients). Percentage of patients with improvement ≥50% in the Bath Ankylosing Spondylitis Disease Activity Index. P <0.0001 from 2 weeks onwards. Modified with permission from [71].
Figure 7
Figure 7
Ankylosing spondylitis: improvement in disease activity. Infliximab sustains improvement in disease activity over 5 years. At 156 weeks, n = 43 patients; at 254 weeks, n = 38. ASAS, Assessment of SpondyloArthritis International Society; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; IFX, infliximab. Modified with permission from [74].
Figure 8
Figure 8
Ankylosing spondylitis: rapid clinical response. Infliximab rapidly improves ASAS40 compared with placebo (n = 279 patients). P <0.001 from 2 weeks onwards. ASAS, Assessment of SpondyloArthritis International Society. Modified with permission from [75].
Figure 9
Figure 9
Ankylosing spondylitis: spinal inflammation. Infliximab completely resolves spinal inflammation in most patients: (a) before-treatment and (b) after-treatment gadolinium-enhanced T1 images. STIR, short-tau inversion recovery. Reproduced with permission from [42].
Figure 10
Figure 10
Psoriatic arthritis: improvement of joint symptoms. Infliximab significantly improves joint symptoms compared with placebo (P <0.001 at week 16) in the IMPACT 1 study (n = 104 patients) [82]. (a) Prior to crossover. (b) Open-label extension, up to 54 weeks. ACR, American College of Radiology.
Figure 11
Figure 11
Psoriatic arthritis: improvement of skin symptoms. Infliximab improves skin symptoms in patients with psoriatic arthritis at week 16 (P < 0.001) and after crossover in the IMPACT 1 study. PASI, Psoriasis Area and Severity Index. Modified from [82].
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References

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