THREAD 1/X Data available from NEW Chinese #Hydroxychloroquine #SARSCoV2 study conflicts with recent French #Hydroxychloroquine (and #Azithromycin) study touted by US politician. zjujournals.com/med/article/20… and mediterranee-infection.com/wp-content/upl… My thoughts:
2/X Both are small pilot studies and REQUIRE FURTHER VALIDATION. Viral load is the endpoint (not clinical outcome). This is important regardless because decrease shedding duration may have important #publichealth implications, and viral burden could impact cytokine storm risk
3/X French study is non-randomized, new Chinese study is randomized. This resulting imbalance in patient characteristics/disposition in French study raises lots of questions. Chinese study only published abstract, so more info is needed, but would tend to have more faith in it
4/X In French study, there was REAL trend toward negative viral load in hydroxychloroquine (HCQ) arm vs untreated comparator even accounting for lost patients not included in analysis. Subset of HCQ treated with azithromycin for BACTERIAL prophylaxis, and had better clearance
5/X in Chinese randomized study, no difference between #Hydroxychloroquine vs control arm in viral load. This is disappointing data. However, devil is in the details and highlights the importance of NOT MAKING CROSS STUDY COMPARISONS.
6/X in China "failed" study patients receive "400 mg per day" per abstract; this suggests once daily but need to see details. French "successful" study received 200 mg three times daily (600 mg daily). So French used higher dose. Also...
7/X The more frequent 3x daily dose in French "successful" study may keep #Hydroxychloroquine levels at therapeutic concentrations compared to "failed" China study using once daily dosing. PK/PD study looking at optimal HCQ dose: academic.oup.com/cid/advance-ar…
8/X The "successful" French study also treated patients longer (14 days) compared to China study (5 days). In French study difference vs control seen as early as 3-6 days so not sure how important these differences in protocols are for viral load. However....
9/X Longer durations of treatment of #Hydroxychloroquine are thought to be better due to intracellular accumulation of drug over time, so perhaps longer therapies could have benefit over short duration. This needs to be studied
10/X #Hydroxychloroquine as high/higher in vitro potency nature.com/articles/s4142… compared to other available drugs like remdesivir nature.com/articles/s4142… and....
11/X #Hydroxychloroquine may have dual indirect antiviral (interfering with steps needed for viral entry) and immunologic (via IL6 inhibition) benefit nature.com/articles/s4158…
12/X Bottom line: at this point: NO CONCLUSIONS CAN BE DRAWN AT THIS POINT BUT despite the conflicting data, #Hydroxychloroquine (w/ or w/o #azithromycin) remains promising given the totality of data (in vitro and clinical). I look forward to seeing more data
13/X Need to re-emphasize, these small studies were evaluating viral load (VL) and NOT clinical outcome (CO). But that's ok in a pilot study. Larger studies will need to look at CO (ie morbidity and mortality). But VL is important for proof of principle, shedding/public health
