Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis

Bijl, A.E. van der; Goekoop-Ruiterman, Yvonne P M; Vries-Bouwstra, Jeska K de; Wolde, S. ten; Han, K.H.; Krugten, M V van; Allaart, Cornelia F; Breedveld, Ferdinand C.; Dijkmans, Ben A. C.

doi:10.1002/art.22718

Cited by 107 publications

(63 citation statements)

References 17 publications

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“…Although higher-dose or dose-escalating treatment did not show statistically better efficacy than standard-dose treatment in several clinical trials 2,4,5,21 , nonresponders at standard-dose treatment have been reported to respond to early dose-escalating treatment 13,22 .…”

Section: Discussionmentioning

confidence: 98%

Prediction of Clinical Response After 1 Year of Infliximab Therapy in Rheumatoid Arthritis Based on Disease Activity at 3 Months: Posthoc Analysis of the RISING Study

Takeuchi

Miyasaka²,

Inui³

et al. 2015

J Rheumatol

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Objective.To investigate the probability of clinical remission (REM) or low disease activity (LDA) after 1 year of infliximab (IFX) therapy based on disease activity at 3 months in patients with rheumatoid arthritis (RA).Methods.Methotrexate-refractory patients with RA received 3 mg/kg of IFX at weeks 0, 2, and 6, followed by 3 mg/kg, 6 mg/kg, or 10 mg/kg every 8 weeks from Week 14 (W14) to Week 46. Correlation of disease activity at W14 with disease activity at W54 and probability of REM/LDA at W54 were analyzed in each dosing group.Results.Disease activities at W14 were significantly correlated with both disease activity at W54 and probability of REM/LDA at W54 in patients continuing 3 mg/kg as well as in those receiving 6 mg/kg or 10 mg/kg therapy from W14. Results showed that, if approximate REM or LDA had not been achieved by W14, > 50% of patients continuing 3 mg/kg therapy would not be able to achieve REM or LDA at W54. However, even in patients with high or moderate disease activity at W14, dose escalation to 6 mg/kg or 10 mg/kg enabled many to achieve REM/LDA.Conclusion.Disease activity at W14 in standard-dose IFX therapy enabled the prediction of longterm clinical response at continued standard dose, as well as subsequent escalated-dose regimens. Disease activity at W14 was hypothesized to be an important index for IFX treatment strategy.

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Section: Discussionmentioning

confidence: 98%

Prediction of Clinical Response After 1 Year of Infliximab Therapy in Rheumatoid Arthritis Based on Disease Activity at 3 Months: Posthoc Analysis of the RISING Study

Takeuchi

Miyasaka²,

Inui³

et al. 2015

J Rheumatol

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“…However, it might work only for a low activity disease [21]. The same authors, two years later, presented data which showed that intraarticular infliximab injection was not effective in patients with a chronically inflamed knee joint [22].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast-Like Synovial Cells in Rheumatoid Arthritis- Impact of Infliximab on Hexosoaminidase Activity

Olszewski¹,

Olszewska²,

Popko³

et al. 2015

Adv Clin Exp Med

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Background. The effect of multiple infusions of infliximab (INF), a chimeric anti-tumor necrosis factor alpha antibody, on the concentration of hexosaminidase (HEX) activity in a synovial cell culture derived from human synovial inflamed fluid obtained from patients suffering from rheumatoid arthritis (RA) has been evaluated. Objectives. The aim of this study was to prove INF efficacy in RA. Material and Methods. Inflamed synovial fluid was taken from RA patients (a study group) and patients who had undergone knee trauma within 7 days (a control group). The following solutions of infliximab were used: 40, 60 and 140 µg/mL. Determination of the concentration of HEX activity in cell cultures was performed after 24, 48, 72 and 96 h of infliximab administration. To identify synoviocytes in cell culture immunohistochemical staining with vimentin and pancytokeratin was performed. Results. A predominance of fibroblast-like synovial cells has been observed in the study group. In the control group the concentration of HEX activity without adding infliximab to the cell culture was 283.00 nkat/mL. After 96 h of incubation with infliximab, the concentrations of HEX activity in cultured synoviocytes according to infliximab doses of 40, 60 and 140 µg/mL were respectively: 280.00, 271.50 and 293.50 nkat/mL. In the study group, the concentration of HEX activity without adding infliximab to the cell culture was 542.27 nkat/mL. The final concentrations of HEX activity of cultured fibroblast-like synovial cells measured after 96 h of incubation with infliximab were: 471.72, 498.27 and 556.72 nkat/mL, according to infliximab doses of 40, 60 and 140 µg/mL. In all groups (besides the infliximab concentration of 140 µg/mL after 96 h of incubation), the level of concentration of HEX activity was significantly higher in the study group compared to the control group, irrespective of infliximab concentration and time of infliximab incubation. Conclusions. Infliximab changes the concentration of HEX activity depending on the drug dose and time of administration (Adv Clin Exp Med 2015, 24, 5, 807-813).

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“…It is now believed that the optimal therapy for early onset RA is a combination of methotrexate with one of the biologics [27]. However, cost often prohibits this approach and unfortunately it is more common to treat with NSAIDs early on in the disease and only progress to the biologics once the disease has worsened considerably.…”

Section: Current Treatment Options For Rheumatoid Arthritismentioning

confidence: 98%

Proteinase-Activated Receptors and Arthritis

Russell

McDougall

2011

Proteases and Their Receptors in Inflammation

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The novel family of proteinase-activated receptors (PARs) is activated through proteolytic cleavage by serine proteinases. This family of G proteincoupled receptors and their activating enzymes are found widely throughout the body. It has been known for some time that during arthritic conditions, high levels of serine proteinases are released from joint tissue and contribute to joint degradation. Expression of PARs is also enhanced in arthritic joints and act to mediate the intracellular signalling of the serine proteinases, leading to various inflammatory and painful effects. This chapter summarises what is known so far on all four of the currently known PARs with respect to their links with arthritis and discusses how these receptors may represent novel targets for the development of new arthritic treatments.

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Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis

Cited by 107 publications

References 17 publications

Prediction of Clinical Response After 1 Year of Infliximab Therapy in Rheumatoid Arthritis Based on Disease Activity at 3 Months: Posthoc Analysis of the RISING Study

Prediction of Clinical Response After 1 Year of Infliximab Therapy in Rheumatoid Arthritis Based on Disease Activity at 3 Months: Posthoc Analysis of the RISING Study

Fibroblast-Like Synovial Cells in Rheumatoid Arthritis- Impact of Infliximab on Hexosoaminidase Activity

Proteinase-Activated Receptors and Arthritis

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