High adalimumab serum concentrations do not result in better response in patients with rheumatoid arthritis (RA), suggesting overexposure. We investigated whether patients with adalimumab ...concentrations >8 µg/mL can prolong their dosing interval by 50% without a clinically relevant change in disease activity.
Consecutive patients with RA, treated with adalimumab 40 mg every other week for at least 28 weeks, were approached for this randomised, open-label, non-inferiority trial. Patients with adalimumab trough concentrations >8 µg/mL were randomly (1:1) assigned to dose-interval prolongation of once every 3 weeks or continuation of every other week. Primary outcome was the change in disease activity score of 28 joints (ΔDAS28-ESR) after 28 weeks, with a non-inferiority margin of 0.6 points.
In total, 147 patients were screened. Fifty-five patients had concentrations >8 µg/mL and were randomised. Mean ΔDAS28 after 28 weeks was -0.14±SD 0.61 in the prolongation group and 0.30±0.52 in the continuation group. Mean difference was significantly in favour of the prolongation group: 0.44 (95% CI 0.12 to 0.76, p=0.01).
Adalimumab-treated patients with RA with trough concentrations >8 µg/mL can prolong their standard dosing interval to once every 3 weeks without loss of disease control.
NTR3509; Results.
Abstract
Objectives
Recently, we demonstrated that early low concentrations of circulating, adalimumab-bound TNF in RA patients treated with adalimumab was associated with future anti-drug antibody ...formation. Furthermore, low TNF was associated with less frequent baseline MTX use. This is remarkable, because of the anti-inflammatory effects of MTX and a potential inhibiting effect on cytokine production. We hypothesized an indirect effect of non-MTX use on low TNF concentrations via immunogenicity. To investigate the effect of MTX on TNF concentrations independent of anti-drug antibody formation, we measured TNF in RA patients treated with etanercept, a drug with low immunogenicity.
Methods
TNF was quantified in 186 consecutive etanercept-treated RA patients at baseline and at weeks 4, 16 and 28. The dynamics of TNF during etanercept treatment were compared with dynamics recently published for adalimumab.
Results
We demonstrated that TNF concentrations at week 4 did not associate with baseline MTX or remission after 28 weeks. Furthermore, median (interquartile range) TNF increased from <112 (<112–<112) pg/ml at baseline to 548 (344–688) pg/ml at week 4 and remained stable at week 16 and 28 598 (442–756) and 568 (444–755) pg/ml, respectively.
Conclusion
Circulating TNF did not associate with MTX usage in etanercept-treated patients. This implies that MTX does not have a direct effect on TNF concentrations in circulation and that the association between early low TNF and non-use of MTX for adalimumab is thus most likely due to anti-drug antibody formation.
Objectives
To evaluate the transition from reference infliximab Remicade to biosimilar Remsima in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA).
Methods
Patients were informed ...through a letter about the transition to a biosimilar and were subsequently contacted for possible additional questions and whether they agreed upon the transition. Once agreed, Remsima was administered at the same dosage and interval as previous treatment with Remicade. Data on the transition were analyzed in January 2018. The primary outcome was the percentage of patients continuing treatment with Remsima and secondary outcome was the change in disease activity measured with the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28‐ESR). In addition, the reasons for discontinuation with infliximab or restarting Remicade were recorded.
Results
In total 47 patients were approached, 45 patients switched from Remicade to Remsima, two patients disagreed upon transition and continued Remicade. At the end of the follow‐up period of 2 years, 39 patients (87%) continued with Remsima, three patients (7%) restarted Remicade due to inefficacy according to the patient (this was not objectified by the rheumatologist) 2 (4%) patients switched to another biological due to lack of effect and in one patient (2%) infliximab was stopped because of lung malignancy. Furthermore, the DAS28‐ESR remained comparable before and after the switch, with a mean (SD) of 2.34 (±1.02) and 2.31 (±1.11) respectively.
Conclusion
In our population, 87% of patients continued Remsima during the follow‐up period of approximately 2 years. Three patients restarted Remicade, while retaining stable DAS28‐ESR.
To observe long-term clinical response and drug survival in a prospective two-year cohort study in rheumatoid arthritis (RA) patients starting adalimumab or etanercept treatment, with or without ...methotrexate (MTX), after failure of conventional DMARD therapy, including MTX.
Disease activity score of 28 joints (DAS28) and Health Assessment Questionnaire (HAQ) were collected of 873 consecutive RA patients, treated with adalimumab or etanercept, prospectively at baseline, 4, 16, 28, 40, 52, 78 and 104 weeks of biological therapy. Sustained minimal disease activity (MDA), DAS28 <2.6 for at least 24 consecutive weeks, biological discontinuation, ΔHAQ and ΔDAS28 were compared between patients treated with or without concomitant MTX for etanercept and adalimumab separately.
More patients treated with adalimumab and MTX (42%) achieved sustained MDA than patients without MTX (18%). The hazard ratio (HR) was 2.3 1.4-3.9. No significant difference was found in etanercept treatment (with MTX 33% vs. 28% without MTX), HR 1.1 0.8-1.6. More patients treated without MTX discontinued treatment than patients with MTX co-treatment in adalimumab (HR 2.1 1.5-3.0) and etanercept (HR 1.9 1.0-3.4). The mean decrease in DAS28 over time was higher for patients treated with MTX in adalimumab (regression coefficient (RC): 0.57, p<0.001), but was not significantly different in etanercept treatment (RC 0.05, p=0.427). No significant differences were found in ΔHAQ.
Treatment discontinuation is lower in patients treated with MTX in both adalimumab and etanercept treatment. However, considering good clinical response, in contrast to etanercept, a synergetic effect of MTX is observed only in adalimumab treatment.
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