Table 2.
Ongoing Clinical Trials on rheumatologic drugs in COVID-19 (last updated on the April 1, 2020).
| Compound | Approved indications for clinical practice in Rheumatology | Potential target viruses | Anti-viral mechanism of action |
|---|---|---|---|
| Glucocorticoids | Several including rheumatoid arthritis, systemic lupus erythematosus, vasculitis | H1N1 | Controversy. Low dose for short time (10 days) may improve acute respiratory distress syndrome. |
| Nonsteroidal anti-inflammatory drugs | Several | CMV, HCV, Flaviviridae, H7N9, H3N2, SARS-CoV | COX-2 inhibition impairs viral replication Spike protein of SARS-CoV inhibited by COX-2 via ERK/NF-kB and PI3K/JNK pathways Ibuprofen effect ACE2 receptor |
|
Chloroquine Hydroxychloroquine |
Rheumatoid arthritis Juvenile idiopathic arthritis Discoid lupus erythematosus Systemic lupus erythematosus |
HIV, HAV, Influenza, HcoV-OC43, FIPV, HcoV-229E, SARS-CoV, SARS-CoV-2 | Increases pH of host cell organelles, impairing enzymatic activity for virus antigen-binding, replication and pro-inflammatory cytokine production and secretion |
| Leflunomide (and teriflunomide) | Rheumatoid arthritis Psoriatic arthritis |
CMV, HSV-1, HSV-2, EBV (teriflunomide), HIV-1, Argentinian mammarenavirus, FMDV, EBOV, Influenza A, Polyomavirus, NDV, EV-A71, RSV | Tyrosine kinase inhibition Inhibition of pyrimidine de novo synthesis through the blockade of dihydroorotate dehydrogenase Possible reduction of IL-6 in vitro |
| Mycophenolate Mofetil | Severe Autoimmune disease (Systemic lupus erythematosus) | Influenza, ZKV, West Nile-virus, Chikungunya, smallpox virus, FMDV, PPRV, Junin virus, norovirus, Lassa's hemorrhagic fever, reovirus, rotavirus, HCV, MERS-CoV | Inhibition IMPDH and conversion of inosine monophosphate to guanosine monophosphate hampering lymphocyte proliferation Increased IFN-stimulated gene expression Synergizes the anti-viral effects penciclovir, lobucavir, 37-fluorodideoxyguanosine, diaminopurine dioxolane of through the depletion of the endogenous GTP pools |
| Methotrexate | ZKV | Inhibition of dihydrofolate reductase | |
| Colchicine | Gout treatment and prevention Acute and recurrent pericarditis Familial Mediterranean fever |
Flaviviridae, RSA59, M − CoV, RSV | Alters cytoskeleton organization via microtubules assembly inhibition Inhibition of the inflammasome Reduction of IL-1 and IL-6 Anti-neutrophilic action |
|
Anakinra Canakinumab Rilonacept |
Rheumatoid arthritis Cryopirin Associated Periodic Syndromes Systemic Juvenile idiopathic arthritis Adult onset Still's disease |
No evidence of direct anti-viral activity Indirect evidence on reduction of inflammatory response in infections by arthritogenic alphavirus and parainfluenza |
IL-1 receptor inhibitor (Anakinra), IL-1β inhibitor (Canakinumab), IL-1α/IL-1β inhibitor (Rilonacept), inhibition of the inflammasome |
| TNFα-inhibitors | Rheumatoid arthritis Juvenile idiopathic arthritis Non-radiographic axial spondyloarthritis Ankylosing spondylitis Psoriasis Psoriatic arthritis |
Rotavirus and indirect evidence on reduction of inflammatory response in infections by influenza viruses | Reduction of inflammatory response |
| Tocilizumab | Rheumatoid arthritis Juvenile idiopathic arthritis |
No evidence of direct anti-viral activity. Indirect evidence on reduction of inflammatory response in COVID-19 |
IL-6 inhibition, inhibition of the cytokine storm? |
| IVIg | Primary immunodeficiency syndromes with impaired antibody production Hypogammaglobulinemia Primary immune thrombocytopenia (ITP) Kawasaki disease |
HAV, HSV, CMV, VZV, EBV, measles, mumps, rubella, parvovirus B19, CMV, hMPV, ADV, RSV, HSV 2, Flaviviridae, HIV, Ebola, SARS-CoV | Direct action both on innate immune components (complement, monocytes, macrophages, natural killer, cells), and on adaptive immune cells (CD4 T-cells and B-cells) Saturate FcR |
| JAK inhibitors | Rheumatoid arthritis Psoriatic arthritis Ulcerative colitis |
No evidence of direct anti-viral activity SARS-CoV-2? Potential reduction of inflammatory response in ALI |
Inhibition of JAK/STAT pathway, reduction of pro-inflammatory cytokines Potential inhibition of AP2-associated protein kinase 1 (AAK1) by baricitinib that SARS-CoV-2 uses to infect lung cells through binding with ACE2 |
| GM-CSFi | Rheumatoid arthritis | Potential reduction of inflammatory response in ALI | GM-CSF neutralization effective in reducing the severity of inflammation |
List of abbreviations: HIV: Human Immunodeficiency Virus, HAV: Hepatitis A Virus, HcoV-OC43: Human coronavirus-OC43, FIPV: Feline infectious peritonitis virus, HcoV-229E: Human coronavirus, SARS-CoV: Severe acute respiratory syndrome-coronavirus, SARS-CoV-2: Severe acute respiratory syndrome-coronavirus-2, CMV: cytomegalovirus, HSV-1: Herpes Simplex Virus-1, HSV-2: Herpes Simplex Virus-2, EBV: Epstein-Barr Virus: FMDV: Foot-and-mouth disease virus, EBOV: Zaire Ebolavirus, NDV: Newcastle disease virus, EV-A71: Non-Polio Enterovirus, RSV: Respiratory Syncytial Virus, ZKV: Zika virus, RSA59: Neurotropic demyelinating strain of MHV, PPRV: peste des petits ruminants virus, HCV: Hepatitis C Virus, MERS-CoV: Middle East respiratory syndrome coronavirus, human metapneumovirus: hMPV, VZV: Varicella Zoster Virus, ADV: adenovirus: ADV; IMPDH: inosine monophosphate dehydrogenase, IFN: interferon, GTP: guanosine triphosphate, ACE2: Angiotensin-converting enzyme 2, interleukin: IL, FcR: Fc receptor, Acute lung injury: ALI