Therapeutic drug monitoring of adalimumab in rheumatic patients

OBJECTIVE and DESIGN Adalimumab (ADA) is effective in the treatment of rheumatoid arthritis IRA), ankylosing spondylitis (ASI and psoriatic arthritis (PsA). Despite suggestions that therapeutic drug monitoring (TDM) of ADA can optimize treatment of this population, it is not routinely implemented in clinical practice. We therefore carried out a prospective observational cohort study by measuring ADA levels in a population of patients with rheumatic diseases and related those levels to disease activity. METHODS Patient demographics were collected from the electronic hospital information system. Blood drawn before the regular outpatient visit was used for determination of ADA trough levels and antibodies against ADA (ATA). Objectified disease activity measurements were obtained at the appointment: DAS28 for RA, ASDAS for AS, and clinical assessment for SpA. RESULTS A total of 17A patients was included. ADA levels varied from less than 0.1 to 22.0 mg/L. The mean ADA level was 6.8 mg/L (standard deviation = 4.2). 5 patients (2,9%) developed ATA. The ADA level was significantly associated with remission (P = 0.002). The mean ADA level was 7.6 mg/L in patients in remission and 5.1 mg/L in patients with active disease. Use of immunosuppressants, frequency of administration, and body mass index were identified as significant covariates. CONCLUSION TDM of ADA demonstrated large interindividual differences in ADA levels. ADA trough levels were significantly associated with disease activity. TDM has the potential to individualize treatment and further research needs to show if it increases cost-effectiveness of this expensive therapy.</p

Therapeutic drug monitoring of adalimumab in rheumatic patients

OBJECTIVE and DESIGN Adalimumab (ADA) is effective in the treatment of rheumatoid arthritis IRA), ankylosing spondylitis (ASI and psoriatic arthritis (PsA). Despite suggestions that therapeutic drug monitoring (TDM) of ADA can optimize treatment of this population, it is not routinely implemented in clinical practice. We therefore carried out a prospective observational cohort study by measuring ADA levels in a population of patients with rheumatic diseases and related those levels to disease activity. METHODS Patient demographics were collected from the electronic hospital information system. Blood drawn before the regular outpatient visit was used for determination of ADA trough levels and antibodies against ADA (ATA). Objectified disease activity measurements were obtained at the appointment: DAS28 for RA, ASDAS for AS, and clinical assessment for SpA. RESULTS A total of 17A patients was included. ADA levels varied from less than 0.1 to 22.0 mg/L. The mean ADA level was 6.8 mg/L (standard deviation = 4.2). 5 patients (2,9%) developed ATA. The ADA level was significantly associated with remission (P = 0.002). The mean ADA level was 7.6 mg/L in patients in remission and 5.1 mg/L in patients with active disease. Use of immunosuppressants, frequency of administration, and body mass index were identified as significant covariates. CONCLUSION TDM of ADA demonstrated large interindividual differences in ADA levels. ADA trough levels were significantly associated with disease activity. TDM has the potential to individualize treatment and further research needs to show if it increases cost-effectiveness of this expensive therapy.</p

Therapeutic drug monitoring van adalimumab bij reumatologische patiënten

OBJECTIVE and DESIGN Adalimumab (ADA) is effective in the treatment of rheumatoid arthritis IRA), ankylosing spondylitis (ASI and psoriatic arthritis (PsA). Despite suggestions that therapeutic drug monitoring (TDM) of ADA can optimize treatment of this population, it is not routinely implemented in clinical practice. We therefore carried out a prospective observational cohort study by measuring ADA levels in a population of patients with rheumatic diseases and related those levels to disease activity. METHODS Patient demographics were collected from the electronic hospital information system. Blood drawn before the regular outpatient visit was used for determination of ADA trough levels and antibodies against ADA (ATA). Objectified disease activity measurements were obtained at the appointment: DAS28 for RA, ASDAS for AS, and clinical assessment for SpA. RESULTS A total of 17A patients was included. ADA levels varied from less than 0.1 to 22.0 mg/L. The mean ADA level was 6.8 mg/L (standard deviation = 4.2). 5 patients (2,9%) developed ATA. The ADA level was significantly associated with remission (P = 0.002). The mean ADA level was 7.6 mg/L in patients in remission and 5.1 mg/L in patients with active disease. Use of immunosuppressants, frequency of administration, and body mass index were identified as significant covariates. CONCLUSION TDM of ADA demonstrated large interindividual differences in ADA levels. ADA trough levels were significantly associated with disease activity. TDM has the potential to individualize treatment and further research needs to show if it increases cost-effectiveness of this expensive therapy

Therapeutic drug monitoring van adalimumab bij reumatologische patiënten

\u3cp\u3eOBJECTIVE and DESIGN Adalimumab (ADA) is effective in the treatment of rheumatoid arthritis IRA), ankylosing spondylitis (ASI and psoriatic arthritis (PsA). Despite suggestions that therapeutic drug monitoring (TDM) of ADA can optimize treatment of this population, it is not routinely implemented in clinical practice. We therefore carried out a prospective observational cohort study by measuring ADA levels in a population of patients with rheumatic diseases and related those levels to disease activity. METHODS Patient demographics were collected from the electronic hospital information system. Blood drawn before the regular outpatient visit was used for determination of ADA trough levels and antibodies against ADA (ATA). Objectified disease activity measurements were obtained at the appointment: DAS28 for RA, ASDAS for AS, and clinical assessment for SpA. RESULTS A total of 17A patients was included. ADA levels varied from less than 0.1 to 22.0 mg/L. The mean ADA level was 6.8 mg/L (standard deviation = 4.2). 5 patients (2,9%) developed ATA. The ADA level was significantly associated with remission (P = 0.002). The mean ADA level was 7.6 mg/L in patients in remission and 5.1 mg/L in patients with active disease. Use of immunosuppressants, frequency of administration, and body mass index were identified as significant covariates. CONCLUSION TDM of ADA demonstrated large interindividual differences in ADA levels. ADA trough levels were significantly associated with disease activity. TDM has the potential to individualize treatment and further research needs to show if it increases cost-effectiveness of this expensive therapy.\u3c/p\u3

Therapeutic drug monitoring (TDM) as a tool in the switch from infliximab innovator to biosimilar in rheumatic patients: results of a 12-month observational prospective cohort study

The objective of this study is to apply therapeutic drug monitoring (TDM) as an objective tool to monitor the switch from infliximab innovator (INX) to infliximab biosimilar (INB) in our diverse rheumatic cohort in daily clinical practice. All rheumatic patients on INX treatment (Remicade®) and ≥18 years were switched to INB (Inflectra®) as part of routine care, but in a controlled setting. Patients were monitored by taking blood samples just before the first infusion of INB (T1), and after the second (T2), fourth (T3), and seventh (T4) infusion of INB. T4 reflects the patients’ status after ∼12 months. Infliximab trough levels, antibodies-to-infliximab (ATI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and validated disease activity scores (if possible) were measured. Our population consisted of 27 patients with seven different rheumatic diseases who had received INX for 143 (58–161) months (median (IQR)). Half of the patients (52%) received concomitant immunosuppressives. We found widely varying infliximab levels, with only 56% within the proposed therapeutic range of 1–5 μg/mL. One patient had very high ATI levels (>880 au/mL), and two had low ATI levels (≤30 au/mL). After switching to INB, seven patients (26%) discontinued the therapy, partially due to subjective reasons. No difference in infliximab levels, CRP levels, and disease activity scores was found between the four time points (p ≥ 0.2460). In conclusion, no pharmacokinetic or clinical differences were found between INX and INB in our diverse rheumatic cohort. TDM is a helpful tool to monitor patients switching from INX to INB

Therapeutic drug monitoring (TDM) as a tool in the switch from infliximab innovator to biosimilar in rheumatic patients:results of a 12-month observational prospective cohort study

\u3cp\u3eThe objective of this study is to apply therapeutic drug monitoring (TDM) as an objective tool to monitor the switch from infliximab innovator (INX) to infliximab biosimilar (INB) in our diverse rheumatic cohort in daily clinical practice. All rheumatic patients on INX treatment (Remicade®) and ≥18 years were switched to INB (Inflectra®) as part of routine care, but in a controlled setting. Patients were monitored by taking blood samples just before the first infusion of INB (T1), and after the second (T2), fourth (T3), and seventh (T4) infusion of INB. T4 reflects the patients’ status after ∼12 months. Infliximab trough levels, antibodies-to-infliximab (ATI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and validated disease activity scores (if possible) were measured. Our population consisted of 27 patients with seven different rheumatic diseases who had received INX for 143 (58–161) months (median (IQR)). Half of the patients (52%) received concomitant immunosuppressives. We found widely varying infliximab levels, with only 56% within the proposed therapeutic range of 1–5 μg/mL. One patient had very high ATI levels (&gt;880 au/mL), and two had low ATI levels (≤30 au/mL). After switching to INB, seven patients (26%) discontinued the therapy, partially due to subjective reasons. No difference in infliximab levels, CRP levels, and disease activity scores was found between the four time points (p ≥ 0.2460). In conclusion, no pharmacokinetic or clinical differences were found between INX and INB in our diverse rheumatic cohort. TDM is a helpful tool to monitor patients switching from INX to INB.\u3c/p\u3

Biologicals en biosimilars : de rol van spiegelbepalingen in therapieoptimalisering en kostenbesparingen

Therapieoptimalisering van anti-TNFα biologicals kan efficiënt gedaan worden met behulp van het meten van geneesmiddelspiegels,\u3cbr/\u3egevolgd door dosisadvies op maat ofwel therapeutic drug monitoring. Om spiegelmetingen in de klinische praktijk te bevorderen heeft\u3cbr/\u3ehet kenniscentrum klinische chemie een infliximab test gevalideerd en in gebruik genomen in nauwe samenwerking met de\u3cbr/\u3eziekenhuisapotheek. Bij het meten van infliximabspiegels in ons ziekenhuis vonden we zeer grote verschillen tussen patiënten, waarbij\u3cbr/\u3eeen significant deel buiten het therapeutisch bereik zat. Hieruit blijkt dat er mogelijk nog winst valt te behalen bij het instellen van\u3cbr/\u3epatiënten op deze zeer kostbare therapie. Met deze test kunnen ook de nieuw verschenen infliximab biosimilars gemeten worden, zodat\u3cbr/\u3ede overstap van geneesmiddelen (originator naar biosimilar) in een gecontroleerde setting, waarbij geneesmiddelspiegels gemeten\u3cbr/\u3eworden, kan plaatsvinden. Therapieoptimalisering van anti-TNFα biologicals kan efficiënt gedaan worden met behulp van het meten van geneesmiddelspiegels,\u3cbr/\u3egevolgd door dosisadvies op maat ofwel therapeutic drug monitoring. Om spiegelmetingen in de klinische praktijk te bevorderen heeft\u3cbr/\u3ehet kenniscentrum klinische chemie een infliximab test gevalideerd en in gebruik genomen in nauwe samenwerking met de\u3cbr/\u3eziekenhuisapotheek. Bij het meten van infliximabspiegels in ons ziekenhuis vonden we zeer grote verschillen tussen patiënten, waarbij\u3cbr/\u3eeen significant deel buiten het therapeutisch bereik zat. Hieruit blijkt dat er mogelijk nog winst valt te behalen bij het instellen van\u3cbr/\u3epatiënten op deze zeer kostbare therapie. Met deze test kunnen ook de nieuw verschenen infliximab biosimilars gemeten worden, zodat\u3cbr/\u3ede overstap van geneesmiddelen (originator naar biosimilar) in een gecontroleerde setting, waarbij geneesmiddelspiegels gemeten\u3cbr/\u3eworden, kan plaatsvinden