A correct understanding of "hydroxychloroquine" rheumatism immunity is its use!

Text . . . Johnson's june 4, 2020, previously published in the Lancet on hydroxychloroquine research paper was withdrawn, the momentary public opinion directly pointed to Surgisphere company suspected of falsifying data; The author believes that in the new crown is still raging around the global background, in the search for effective drugs at the same time, it is more important to scientific rational understanding of drugs, especially this for antimalarial, rheumatic immune direction for nearly 65 years of good medicine! 1 hydroxychloroquine and drug introduction hydroxychloroquine (hydroxychloroquine, HCQ), structurally belongs to 4-aminoquinasiase A2 inhibitor, is a traditional antimalarial drug, in 1955 in the United States FDA approved the market, clinically used for the treatment of malaria acute onset and control, disc lupus, systemic lupus, acute chronic rheumatoid arthritis, etc.
2007-2017, the species ranked among the top 200 most commonly used prescription drugs in the United States, with an average annual prescription volume of more than 5 million, and on March 28, 2020, the FDA issued an Emergency Use Authorization (EUA) to allow oxyphymesulin sulfate to be used to treat certain hospitalized COVID-19 patients.
Figure 1.1: chloroquine/hydroxychloroquine/Miparin chemical structure (Photo source: doi: 10.1038/nrrheum.2012.106) 2 Development process. "From golden chicken to hydroxychloroquine" hydroxychloroquine, the earliest antimalarial drug... The antimalarial drug originated in Peru's golden chicken bark and was globally distributed in the 1630s, when the Spanish Governor-General and Countess in Peru cured malaria by using the bark of the golden chicken, and then followed by a mission to Europe; Two famous pharmacologists successfully extracted alkaloid "quinin" and "sincorn" from the bark of Jinjina, thus the world's first synthetic antimalarial drug was born; During World War II, the world began to develop new antimalarial drugs, best known as the yellow "American Miparin", which was used by the military to prevent malaria and was found to significantly improve the level of rheumatoid rashes and arthritis; 35 cases of pythemutoxatosus, mainly to relieve the symptoms of lupus light allergy, in 1949, scientists developed a new generation of antimalarial drug "chlorpyrifos" to market, and gradually replaced the quinine, but with the widespread use, drug resistance began to appear, And regardless of malaria or rheumatism, the treatment window is obviously very narrow, and the existence of the most destructive irreversible "cow's eye"-like retinopathy; Similarly, the difference is only that ethyl in the chloroquine structure is modified as hydroxyethyl, and its risk of "retinal lesions" is much lower than chloroquine, and is widely used in various rheumatoid immune diseases;
Figure 2.1: Antimalarial Drug Development and Important Timeline (Photo Source: s41584-020-0372-x) 3 hydroxychloroquine and autoimmune mechanisms and cellular effects Nature Review reports on the role of hydroxychloroquine in the direction of autoimmune diseases Mechanism: It can enter the lysosome along the pH gradient, and form a accumulation, and with the accumulation of quantity, will change the pH state of the lysosome, thus changing the activity of the enzyme;
in addition to the above mechanism, hydroxychloroquine can also accumulate in the body and bind to double-stranded DNA, also by changing the body's pH, and to prevent the activation of TLR7 and TLR9 to inhibit toll-like receptor signal conduction;
Figure 3.1: Hydroxychloroquine and autoimmune mechanism (photo source: s41584-020-0372-x) Based on the above mechanism of action, hydroxychloroquine can also inhibit antigen activation in B cells The process is transmitted to a lower level of T cells, thereby preventing The activation of T cells and the differentiation and expression of co-stimulated molecules such as CD154, and reducing the production of cytokines (e.g. IL-1, IL-6, and TNF) in T-cells and B cells.
Figure 3.2: Hydroxychloroquine and autoimmune cell effects (Image source: s41584-020-0372-x) 4 hydroxychlorochloroquine and clinicaluse for a variety of "severe diseases" hydroxychloroquinyl In addition to the textbook as a typical case of antimalarial drugs, in most hospitals, the highest frequency of the department is "rheumatic immunity", in this department, the doctor's use of the drug, similar to the ordinary family often prepared cold fever medicine, the occurrence of a very high frequency! At present, hydroxychloroquine has been used in a number of clinical indications, such as systemic lupus lupus, interstitial pneumonia, rheumatoid arthritis, aggressive spinabitis, antiphospholipid syndrome, nephropathy syndrome, recurrent rheumatism, eosinophilis, dermatitis, dry syndrome and other "serious diseases", with good safety and reliable efficacy! The following focuses on the use of some diseases.
NO1 - Systemic lupus systemic lupus erythematosus (SLE) is a diffuse connective tissue disease characterized by immune inflammation, which is a multi-system system in the whole body and has a variety of autoantibodies in the serum.
in sLE activity and the more serious disease, hormone shock combined immunosuppressant treatment, the disease induced after the relief, then receive maintenance therapy.
maintenance treatment mainly depends on oral glucocorticoids, and the long-term application of hormones may cause blood sugar, blood lipid metabolism abnormalities and electrolyte disorders, sodium water storage, osteoporosis and other side effects.
hydroxychloroquine as the basic drug for the treatment of SLE, is now widely used in clinical practice.
Figure 4.1: Lupus-TLR-mediated congenital immunosuppressive effect NO2-interstitial pneumonia (ILD) ILD is a basic pathological change with diffuse alplicosis, pulmonary substance and interstitial fibrosis, with active breathing difficulties, restrictive ventilation disorders, hypoxemia as the main clinical manifestations.
there is no specific treatment, the preferred drug in clinical treatment is immunosuppressant glucocorticoids.
1984-2013, foreign scholars reported a total of 85 cases of CQ and HCQ, or other drugs used in the treatment of ILD patients;
at the same time, a summary of the treatment of HCQ use in several cases of SFTPC gene mutation-caused ILD, found that 12 patients with HCQ alone had good results, no adverse drug reactions were found during treatment or were not mentioned due to minor adverse reactions;
NO3-antiphospholipid syndrome (APS) APS is a group of autoimmune diseases associated with antiphospholipid antibodies, mainly clinically manifested as recurrent arterial or venous thrombosis and pathological pregnancy (early pregnancy abortion, mid- to late stillbirth, etc.) and platelet reduction, the incidence rate of women is significantly higher than men.
at the 13th International Symposium on Antiphospholipid Syndrome, the proposal to give APS combined thrombosis patients hydroxychloroquine supplementary treatment can improve the outcome of pregnancy.
clinical studies show that HCQ has immunomodulation function, can be combined with conventional anticoagulant therapy to improve the pregnancy outcome of patients with refractory APS, effectively reduce the rate of early abortion, and HCQ toxic side effects are small, better tolerance, HCQ can also prevent osteoporosis in patients, can be coordinated with low-molecular heagulin anticoagulant effect.
NO4 - Refractor Nephropathy Syndrome (RNS) RNS is a common clinical kidney disease, high incidence, and high clinical recurrence rate, long-term incurable treatment may lead to patients with acute renal failure, severe infection, thromboembolism syndrome and other fatal complications, which become chronic renal failure after life-threatening.
the current clinical treatment of the disease is mostly using immunosuppressant combination hormone therapy.
clinical studies show that cyclophosphamide combined with HCQ and hormone administration can reduce the patient's urine protein quantification, glutamate transaminase, increase albumin, reduce the occurrence of adverse reactions.
, both HCQ and immunosuppressant leflunometus have immunomodulation function, in the treatment of RNS patients, the use of HCQ combined to fluoromete can play a synergy, the incidence of later adverse reactions in patients significantly reduced.
5 hydroxychloroquine and domestic market registration declaration due to the variety has been listed for decades, regardless of domestic and foreign, has been a mature variety.
domestic aspects, in addition to the original Sino-Nonfi (Seneng) to obtain domestic import approval, the domestic pharmaceutical company Shanghai Pharmaceuticals China and the West Pharmaceuticals (Yule), Chongqing Fu'an Pharmaceutical, Wuhan Wu pharmaceutical, Jiangsu Shenhua Pharmaceuticals, Suzhou Long March-Xinkai Pharmaceuticals and other enterprises for the declaration of the variety, have received production approval.
but on the whole, whether hospitals or pharmacies, for the variety of favor, mainly concentrated in the original study of "Sai Neng", as well as imitation of the "joy".
and drug prices, the original Study Sanofi products "Seneng" (200mg x 10) price in 50-60 yuan / box or so;
summary since the outbreak of the new crown, hydroxychloroquine has been used in clinical trials, the author has been very worried, very worried about the drug market out of stock situation, after all, this drug for rheumatic immune department patients, too important! Rheumatic immunology drugs, multi-system treatment, complex drug use, the use of hydroxychloroquine, can greatly reduce the use of hormones and some immunosuppressants do notage, and at the same time stress edified that this is a good medicine, because even if the patient is pregnant, can also take! Therefore, hydroxychloroquine is very important for rheumatoid immunity treatment! At the same time, however, there is great concern about "abuse" due to the epidemic, as the long-term use of hydroxychloroquine will significantly increase the risk of damage to the bottom of the eye, with accumulation and dose dependence.
therefore, the author of the variety of its most extensive clinical use of the introduction, in order to hope that we can objectively and scientifically look at this decades of verification of the "good medicine"! Reference 1. Nat. Rev. Rheumatol. online advance publication 17 July 2012. doi: 10.1038/nrrheum.2012.1062. Nature Reviews Rheumatology.s41584-020-0372-x3. Back to Park: Did the political leanings of scientists influence clinical studies of hydroxychloroquine? 》4. Progress of hydroxychloroquine in the treatment of systemic lupus. CNKI5. Advances in the Clinical Application of Hydroxychloroquine. CNKI6. The Journey of Hydroxychloroquine against Rheumatism 7. Drug data.