慢性疼痛：腰痛・変形性膝・股関節症へのオピオイド処方は非オピオイド比較して有効とは言えない

Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain
The SPACE Randomized Clinical Trial
Erin E. Krebs,  et al.
JAMA. 2018;319(9):872-882. doi:10.1001/jama.2018.0899
https://jamanetwork.com/journals/jama/article-abstract/2673971

慢性腰痛、股部・膝変形性関節症の中等度以上重症疼痛患者に対して、オピオイド系 vs 非オピオイド処方の疼痛関連機能改善効果の比較

RCT、240名

Nonopioid Prescribing Strategy

• Step 1 was acetamino- phen (paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs).
• Step 2 included adjuvant oral medications (ie, nortriptyline, amitriptyline, gabapentin) and topical analgesics (ie, capsaicin, lidocaine). 
• Step 3 included drugs requiring prior authorization from the VA clinic (ie, pregabalin, duloxetine) and tramadol. 

Patients were initially prescribed a step 1 medication, unless all were clinically inap- propriate. Subsequent changes included titrating, replacing, or adding medications.

Opioid Prescribing Strategy

Per protocol, patients in the opioid group started taking immediate-release (IR) opioids.

• Step 1 was morphine IRhydrocodone/acetaminophen, and oxycodone IR. 
• Step 2 was morphine sustained-action (SA) and oxycodone SA. 
• Step 3 was transdermal fentanyl. 

Single-opioid therapy was preferred, but dual therapy with a scheduled SA opioid and as-needed IR opioid was considered based on patient needs and preferences.
Opioids were titrated to a maximum daily dosage of 100 morphine-equivalent (ME) mg.
If dosages were titrated to 60 ME mg/d without a response, rotation to another opioid was considered before dosage escalation.

プライマリアウトカム:12ヶ月時点での疼痛関連機能　 (Brief Pain Inventory [BPI] interference scale) :1ポイント改善で臨床的意義
www.npcrc.org/files/news/briefpain_short.pdf
プライマリ・副作用アウトカム:薬品関連症状(患者報告チェックリスト:range 0-19)

平均年齢 58.3歳、女性　32(13.0%)、トライアル完遂 234 (97.5%)
疼痛関連機能について群間差１２ヶ月時点で認めない 、全体 P = 0.58
平均１２ヶ月BPI interferenceは　オピオイド群 3.4 、非オピオイド 3.3 (差 0.1 ,95% cI, -0.5 to 0.7)
疼痛強度は12ヶ月間、非オピオイド群で有意に良好  (overall P = .03); mean 12-month BPI 重症度 オピオイド群 4.0 vs 非オピオイド群  3.5  (差, 0.5 [95% CI, 0.0 to 1.0])

薬剤副作用症状はオピオイド群が12ヶ月間常に多い  (overall P = .03); 平均薬剤関連症状 オピオイド群 1.8 、非オピオイド群 0.9  (差, 0.9 [95% CI, 0.3 to 1.5])

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オピオイド系薬剤使いすぎじゃないかと思われるケースを散見する


NSAIDsによる心血管疾患イベント増加、腎障害、いわゆるアスピリン喘息などを考えると、NSAIDｓ忌避傾向は当然なのかもしれない

だが、オピオイド系が安全というわけでもない
さらに、有効性も今ひとつとなると、オピオイド薬剤のbenefit/harmバランス再考必要