Cílem článku je shrnout závažné lékové interakce nesteroidních antirevmatik, imunosupresiv, antimalarik, glukokortikoidů, biologických a cílených syntetických chorobu modifikujících antirevmatických léků s léky používanými ve vnitřním lékařství.

This report summarizes important interactions of non‑steroidal anti‑inflammatory drugs, immunosupressants, antimalarial drugs, glucocorticosteroids, biological and targeted synthetic disease‑modifying antirheumatic drugs with drugs commonly used in internal medicine.

• MeSH
• amiodaron aplikace a dávkování   farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• antiflogistika nesteroidní farmakokinetika   farmakologie   terapeutické užití   MeSH
• antimalarika farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• antirevmatika * farmakokinetika   farmakologie   terapeutické užití   MeSH
• azathioprin farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• cyklofosfamid farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• cyklosporin farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• glukokortikoidy farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• inhibitory proteinkinas farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• inhibitory protonové pumpy farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• kombinace léků trimethoprim a sulfamethoxazol farmakokinetika   farmakologie   škodlivé účinky   MeSH
• leflunomid farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• lékové interakce MeSH
• lidé MeSH
• metabolické vedlejší účinky léčivých látek MeSH
• penicilamin farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• revmatické nemoci farmakoterapie   MeSH
• sulfasalazin farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• TNF-alfa antagonisté a inhibitory   farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• warfarin farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

• MeSH
• antirevmatika * aplikace a dávkování   farmakokinetika   farmakologie   klasifikace   škodlivé účinky   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• muskuloskeletální bolest farmakoterapie   MeSH
• osteoartróza * farmakoterapie   MeSH
• randomizované kontrolované studie jako téma MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH

BACKGROUND: ABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments. RESULTS: A total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups. CONCLUSIONS: These efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.

• MeSH
• antirevmatika farmakokinetika   terapeutické užití   MeSH
• biosimilární léčivé přípravky farmakokinetika   terapeutické užití   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• infliximab farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• revmatoidní artritida farmakoterapie   patologie   MeSH
• senioři MeSH
• terapeutická ekvivalence MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Lékové interakce se v současné době poměrně běžně vyskytují jak při poskytování ambulantní péče, tak i u hospitalizovaných pacientů. Výskyt lékových interakcí je v podmínkách České republiky častější u žen a roste s věkem pacientů, což souvisí s počtem užívaných léčiv. V oboru revmatologie se standardně používají léčiva, která mají vysoký interakční potenciál, jako je např. metotrexát nebo leflunomid. Přehledný článek podává informaci o hlavních mechanismech lékových interakcí chorobu modifikujících antirevmatických léků (disease‑modifying antirheumatic drugs, DMARDs), včetně biologických léčiv.

Drug interactions are currently relatively common both in outpatient care and in hospitalized patients. The occurrence of drug interactions in the Czech Republic is more frequent among women and increases with the age of patients which is related to the number of drugs used. In the field of rheumatology, drugs that have a high interaction potential, such as methotrexate or leflunomide, are commonly used. The review article provides information on the main mechanisms of drug interactions of disease‑modifying antirheumatic drugs (DMARDs), including biological drugs.

• MeSH
• antagonista receptoru pro interleukin 1 MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• antigeny CD20 farmakologie   MeSH
• antirevmatika farmakokinetika   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• lékové interakce MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• receptory interleukinu-6 antagonisté a inhibitory   MeSH
• revmatické nemoci * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

PURPOSE: Andecaliximab (GS-5745) is a highly selective monoclonal antibody against matrix metalloproteinase-9 (MMP9), a proteolytic enzyme implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the safety and pharmacokinetic (PK) parameters of andecaliximab in patients with RA and evaluated the effects of andecaliximab treatment on exploratory disease biomarkers. METHODS: In this double-blind, Phase 1b trial, patients with active RA were randomized (4:1) to receive 400-mg andecaliximab or placebo every 2 weeks for a total of 3 intravenous infusions. The primary and secondary end points were safety and the PK parameters of andecaliximab, respectively. Data were summarized by using descriptive statistics. FINDINGS: A total of 18 patients were randomized; 15 received andecaliximab (participants with confirmed RA diagnosis without current administration of a biologic DMARD a biologic DMARD (disease-modifying antirheumatic drug), aged 18 to 70 years old, weighing >45 to <120 kg). No deaths, serious adverse events, or study discontinuations occurred. All reported adverse events were grade 1 or grade 2 in severity. Mean plasma andecaliximab exposure was 587 d · µg/mL and 878 d · µg/mL at days 1 and 29, respectively, suggesting moderate accumulation. The median terminal t1/2 was 5.65 days; mean volume of distribution at steady state was 4560 mL. Mean MMP9 coverage (the percentage of total plasma MMP9 bound by therapeutic antibody) was maintained at ~80% after the first administration of andecaliximab. IMPLICATIONS: Andecaliximab administered as 3 infusions over 29 days was generally safe and well tolerated in patients with RA. The majority of total plasma MMP9 was bound by andecaliximab after the first administration. Clinical studies of increased treatment duration in larger patient cohorts are warranted. ClinicalTrials.gov identifier: NCT02176876. Registered on 25 June 2014.

• MeSH
• antirevmatika * škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• inhibitory matrixových metaloproteinas * škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• intravenózní infuze MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• monoklonální protilátky * škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: This double-blind, active-controlled, randomized, multinational study evaluated the efficacy, safety, pharmacokinetics (PK), and immunogenicity of PF-06438179/GP1111 (IxifiTM/Zessly®), an infliximab biosimilar, vs infliximab (Remicade®) reference product sourced from the European Union (infliximab-EU) in biologic-naïve patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate therapy. This paper reports results from the initial 30-week treatment period. METHODS: Patients (N = 650) were stratified by geographic region and randomized 1:1 to PF-06438179/GP1111 or infliximab-EU (3 mg/kg intravenous at weeks 0, 2, and 6, then every 8 weeks). Dose escalation to 5 mg/kg was allowed starting at week 14 for patients with inadequate RA response. The primary endpoint was American College of Rheumatology criteria for ≥ 20% clinical improvement (ACR20) response at week 14. Therapeutic equivalence was declared if the two-sided 95% CI for the treatment difference was within the symmetric equivalence margin of ± 13.5%. Statistical analysis was also performed with a two-sided 90% CI using an asymmetric equivalence margin (- 12.0%, 15.0%). RESULTS: Patients (80.3% female; 79.4% seropositive) had a mean RA duration of 6.9 years, and mean baseline Disease Activity Score in 28 joints, four components based on C-reactive protein was 6.0 in both arms. Week 14 ACR20 in the intention-to-treat population was 62.7% for PF-06438179/GP1111 and 64.1% for infliximab-EU. Week 14 ACR20 using nonresponder imputation was 61.1% for PF-06438179/GP1111 and 63.5% for infliximab-EU, and the 95% (- 9.92%, 5.11%) and 90% (- 8.75%, 4.02%) CIs for the treatment difference (- 2.39%) were entirely contained within the prespecified symmetric and asymmetric equivalence margins, respectively. No differences were observed between arms for secondary efficacy endpoints. Overall postdose antidrug antibody (ADA) rates through week 30 were 48.6% and 51.2% for PF-06438179/GP1111 and infliximab-EU, respectively. Efficacy and immunogenicity were similar between treatments for patients with dose escalation (at or after week 14), as well as between treatments for patients without dose escalation. Safety profiles of PF-06438179/GP1111 and infliximab-EU were similar, with no clinically meaningful differences observed between arms, including after ADA development. Serum drug concentrations were similar between arms at each time point during the initial 30-week treatment period. CONCLUSION: PF-06438179/GP1111 and infliximab-EU demonstrated similar efficacy, safety, immunogenicity, and PK with or without dose escalation in patients with moderate to severe active RA on background methotrexate. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02222493 . Registered on 21 August 2014. EudraCT, 2013-004148-49 . Registered on 14 July 2014.

• MeSH
• antirevmatika farmakokinetika   terapeutické užití   MeSH
• biosimilární léčivé přípravky farmakokinetika   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• infliximab farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři MeSH
• terapeutická ekvivalence MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• analgetika aplikace a dávkování   klasifikace   MeSH
• antagonisté prostaglandinu farmakologie   MeSH
• antirevmatika * aplikace a dávkování   farmakokinetika   farmakologie   klasifikace   metabolismus   škodlivé účinky   MeSH
• artritida farmakoterapie   MeSH
• bolest farmakoterapie   MeSH
• cyklooxygenasy fyziologie   MeSH
• lékové interakce MeSH
• lidé MeSH
• měření bolesti klasifikace   MeSH
• nežádoucí účinky léčiv klasifikace   MeSH
• nociceptivní bolest farmakoterapie   MeSH
• opioidní analgetika aplikace a dávkování   farmakologie   klasifikace   MeSH
• paracetamol aplikace a dávkování   farmakologie   MeSH
• prostaglandiny biosyntéza   fyziologie   MeSH
• revmatické nemoci * farmakoterapie   MeSH
• riziko MeSH
• tramadol aplikace a dávkování   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVES: To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. RESULTS: 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was -1.88% (95% CI -10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. CONCLUSIONS: SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. TRIAL REGISTRATION NUMBER: NCT01936181.

• MeSH
• antirevmatika škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• biosimilární léčivé přípravky škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• infliximab škodlivé účinky   imunologie   farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• protilátky krev   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• terapeutická ekvivalence MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

OBJECTIVES: To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. METHODS: This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. RESULTS: 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). CONCLUSIONS: SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN. TRIAL REGISTRATION NUMBERS: NCT01895309, EudraCT 2012-005026-30.

• MeSH
• antirevmatika škodlivé účinky   imunologie   farmakokinetika   terapeutické užití   MeSH
• biosimilární léčivé přípravky škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• etanercept škodlivé účinky   imunologie   farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• protilátky krev   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři MeSH
• terapeutická ekvivalence MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

OBJECTIVES: ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. METHODS: In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. RESULTS: A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. CONCLUSIONS: Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. TRIAL REGISTRATION NUMBER: NCT01970475; Results.

• MeSH
• adalimumab škodlivé účinky   terapeutické užití   MeSH
• antirevmatika škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• biosimilární léčivé přípravky škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• protilátky krev   MeSH
• revmatoidní artritida krev   farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• terapeutická ekvivalence MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH