類風濕性關節炎:確認標靶藥物Adalimumab的濃度


  【24drs.com】荷蘭研究者在線上發表於12月10日風濕性疾病誌的文獻指出,Adalimumab (Humira, AbbVie Inc)血中濃度5-8 μg/mL時對於類風濕性關節炎(rheumatoid arthritis,RA)疾病活性的效果最大,病患同時服用methotrexate (MTX)時,可以用最低劑量的adalimumab達到建議的血中濃度。
  
  根據荷蘭阿姆斯特丹Sanquin Research and Landsteiner Laboratory Academic Medical Centre免疫病理科、Jan van Breemen研究院Gertjan Wolbink醫師指出,Adalimumab最低濃度大於8 μg/mL時對於疾病活性並無額外助益。
  
  研究者的目標是確認adalimumab用於RA時的濃度-效益曲線,以鑑別治療範圍並促進該藥的最大經濟效益,據美國研究者估計,每名RA患者每年所需費用為16,978美元。
  
  這篇前瞻觀察型世代研究檢視了221名病患每週的adalimumab最低濃度與臨床效果,這些病患每兩週以40 mg的adalimumab皮下注射給藥治療28週,根據病患是否併用MTX進行分類;根據28個關節的疾病活性分數測量疾病活性,根據歐洲抗風濕聯盟反應準則將病患分類為良好反應者、無反應者或適度反應者。
  
  作者們寫道,Adalimumab最低濃度範圍5–8 μg/mL即足以達到適當臨床反應,這些數據受到併用MTX之實質影響。
  
  追蹤28週時,單純接受adalimumab治療者的平均adalimumab濃度為4.1 μg/mL,同時使用MTX者之adalimumab濃度則是7.4 μg/mL(P < .001)。
  
  研究者認為,MTX或許是因為降低發炎而促成增加adalimumab血中濃度,降低adalimumab需結合的標靶數;因此,我們可以結論,至少在治療的最初6個月,即使併用低劑量的MTX也可優化adalimumab之治療,因為病患服用MTX時需要較低劑量的adalimumab以獲得具最大臨床效益的有效濃度。
  
  Wolbink醫師表示,臨床已經可以用實驗室測量adalimumab血中濃度,他會建議在6個月時至少測一次adalimumab血中濃度,或者發現治療效果不足時測量看看。我們這次研究結果解答了一個重要問題:「adalimumab用於RA的治療範圍是什麼」,並提出我們為什麼不例行性測量這個濃度的原因。
  
  Eric L. Matteson醫師表示,應用這項監測所需的檢測方式不貴,對於adalimumab如何行銷將會帶來改變。
  
  明尼蘇達州羅徹斯特梅約診所類風濕科主任、未參與此次研究的Matteson醫師表示,如果監測方式便宜,如果它有可能降低人們的藥物劑量,這將是值得考慮的,藥物必須有可以彈性劑量給藥的設計,這部份目前還沒有。就實務面看來,因為這些數據是總和資料,我們不知道哪些病患可以藉由這個治療濃度達到目標、哪些不會,所以,藥物處方決策仍舊是由醫師決定,根據臨床反應評估病患。
  
  檢測adalimumab值目前可用荷蘭的Sanquin Diagnostic Services以及加州聖地牙哥的Prometheus Laboratories,後者行銷Anser ADA檢測方法以監測發炎性腸道疾病患者之adalimumab藥物值以及antiadalimumab抗體值,要價250.00美元。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=7038&x_classno=0&x_chkdelpoint=Y
  

Rheumatoid Arthritis: Target Adalimumab Level Determined

By Janis C. Kelly
Medscape Medical News

Adalimumab (Humira, AbbVie Inc) blood levels of 5 to 8 μg/mL had the greatest effect on rheumatoid arthritis (RA) disease activity, Dutch researchers report in an article published online December 10 in the Annals of the Rheumatic Diseases. Patients taking concomitant methotrexate (MTX) reached the recommended blood levels at lower doses of adalimumab.

Adalimumab trough levels greater than 8 μg/mL had no additional beneficial effect on disease activity, according to Gertjan Wolbink, MD, from the Jan van Breemen Research Institute/Reade and the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.

The researchers' goal was to determine the concentration–effect curve of adalimumab in RA to identify a therapeutic range and facilitate the most cost-effective use of this drug, which US researchers have estimated costs $16,978 per patient with RA per year.

The prospective observational cohort study examined clinical efficacy and weekly adalimumab trough levels in 221 consecutive patients treated with 40 mg adalimumab subcutaneously every other week for 28 weeks. Patients were stratified according to whether or not they were taking MTX. Disease activity was measured using the disease activity score in 28 joints, and patients were categorized as good responders, nonresponders, or moderate responders using European League Against Rheumatism response criteria.

"Adalimumab trough levels in a range of 5–8 μg/mL are sufficient to reach adequate clinical response. These levels are influenced substantially by concomitant MTX use," the authors write.

Mean adalimumab levels at 28 weeks of follow-up were 4.1 μg/mL in patients receiving adalimumab monotherapy and 7.4 μg/mL in patients who were also receiving MTX (P < .001).

The researchers suggested that MTX might contribute to increasing adalimumab blood levels by reducing inflammation and lowering the number of targets for adalimumab to bind to. "Therefore, we can conclude that even the use of a low concomitant MTX dose aids in optimising treatment with adalimumab, at least during the first 6 months of treatment, since patients taking MTX might need a lower dose of adalimumab to obtain an effective concentration with maximal clinical benefits," the authors write.

Dr. Wolbink told Medscape Medical News that laboratory tests for measuring adalimumab blood levels are readily available for clinical use. "I would recommend testing the adalimumab blood level at least once at 6 months or when therapy is not effective enough," he said. "The results of our study answer one important question [What is the therapeutic range for adalimumab in RA?] and raise the question of why we do not test the level routinely."

Eric L. Matteson, MD, MPH, told Medscape Medical News that applying the proposed monitoring will require that tests be inexpensive and that there be a change in how adalimumab is marketed.

"If the monitoring is cheap, it could be something to consider if it makes it possible to reduce the dose of the drug. The drug would have to be available in flexible dosing aliquots, which currently it is not. From a practical point of view, since the levels are summary data, we don't know which patients will be the ones who will be able to get by on these levels, and which won't, so drug prescription decisions will still be driven by doctor and patient assessments of clinical response," said Dr. Matteson, who is chair of the Division of Rheumatology at the Mayo Clinic, Rochester, Minnesota, and who was not involved in this study.

Tests for adalimumab levels are currently available from Sanquin Diagnostic Services in the Netherlands and from Prometheus Laboratories, San Diego, California, which markets the Anser ADA test for monitoring of adalimumab drug levels and antiadalimumab antibody levels in patients with inflammatory bowel disease, at a cost of $250.00.

The study was funded by an unrestricted grant of Wyeth Pharmaceuticals. One coauthor has received consultancy fees from Abbott, Roche, Pfizer, MSD, UCB, BMS, and Wyeth and payment for lectures from Abbott, Roche, and Pfizer. One coauthor has received honoraria for lectures from Pfizer and AbbVie. One coauthor has received honoraria for lectures from Abbott, Roche, and Pfizer. One coauthor has received honoraria for lectures from Pfizer, AbbVie, and UCB. Dr. Wolbink has received a research grant from Wyeth Pharmaceuticals and honoraria for lectures from Amgen, UCB, BMS, AbbVie, and Pfizer. Dr. Matteson has disclosed no relevant financial relationships.

Ann Rheum Dis. Published online December 10, 2013.

    
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