Autoimmune diseases increasingly are treated with agents that block tumor necrosis factor-α (TNF) through various mechanisms. One of these agents, infliximab (Remicade), carries a substantial risk for reactivating tuberculosis in people with latent disease. This tendency was not found during clinical trials of a second TNF-blocking agent, etanercept (Enbrel), but FDA researchers received 25 reports of etanercept-associated reactivated TB in the first 40 months after the drug was marketed.

Most patients (age range, 9-84) had taken etanercept for rheumatoid arthritis, and 21 of 25 were taking other immunosuppressants (most commonly, methotrexate, steroids, or both) at the same time. Tuberculosis developed at a median of 11.5 months after etanercept initiation (range, 1-20 months). Most patients had extrapulmonary involvement, including lymphatic, meningeal, and disseminated disease. Two patients died, one from tuberculosis directly.

In a voluntary reporting program for TNF-antagonist-associated TB in California, researchers received reports of 11 TB cases associated with infliximab and of 1 case associated with etanercept during 19 months. All patients except 1 were born outside the U.S. or had other risk factors for TB; only 5 underwent tuberculin testing before beginning TNF-antagonist therapy.

Comment: Voluntary reporting data do not allow precise calculation of the relative risks of TB reactivation with these drugs. Clearly, patients who are considered for either therapy must be screened rigorously for the presence of latent TB; a convincing history of TB exposure could be grounds for prophylaxis, even in the absence of a positive skin test. Some experts suggest postponing TNF-antagonist treatment until TB prophylaxis is complete. The same cautions probably apply to adalimumab (Humira), the newest TNF-blocker on the block.

— Abigail Zuger, MD

Published in Journal Watch General Medicine September 3, 2004

所以病人使用TNF抗體前必須檢查胸部X光，確定沒有肺結核。再做二次PPD Test，如果陽性反應則給予9個月預防治療，投藥二週後即可給TNF抗體。如果陰性即可給予TNF抗體。

回到主題，為何不行？

其實已經有人針對這一點寫了專文，在The Journal of Rheumatology 2005;32 Suppl 74:35-39

標題為Why Does Tumor Necrosis Factor Targeted Therapy Reactivate Tuberculosis，有興趣可以參考看看。

如果你很不想看英文，我寫了點簡單的病理說明：

腫瘤壞死因子雖然可以活化單核球去吞噬身體裡面的細菌等侵入物，但是也會促進體內的肉芽組織生成，此時就會將結核菌包在裡面，無法擴散，成形肺結核或是肺外結合。但是當使用腫瘤壞死因子抑制劑以後，會將原先形成的肉芽組織破壞，也會讓後來的肉芽組織無法形成，使結核菌往外擴散，造成大範圍或是全身性的結核症。

在歐美等國家，因為結核病患本來就比例較少，但是卻因為注射了TNFα抑制劑之後有明顯增加的趨勢，尤其是infliximab案件最多，所以在歐美等國家，要使用TNFα抑制劑之前，必須先對患者進行結核菌皮下試驗或是Quantiferon，如果結核菌皮下試驗反應結果超過5mm，則表示為潛在的結核病患，必須先進行一個月以上的結核病治療，才可以開始使用TNFα抑制劑。