Table 2.

Details of clinical trials, observational studies and dedicated case series reporting safety and efficacy of leflunomide and teriflunomide in COVID-19. (N.A. = not applicable).

S. No	Study design	Population	Intervention	Control	Co-interventions	Outcome	Comment	References
1	Open label Randomized controlled trial	Lab confirmed (RT-PCR) moderate COVID-19 patients (Moderate as per NHC, 2020; China),	Leflunomide 50 mgm 12 hourly three times daily than 20 mg every day for total 10 days. N = 5	Blank control N = 5	Arbidol, Lianhua qingwen capsule (traditional medicine), magnesium isoglycyrrhizinate & cefoperazone.	Time from leflunomide initiation to discharge, length of hospitalization, duration of viral shredding and safety.	2 patients in each group showed COVID-19 PCR negativity, however, there were obvious lung inflammatory opacities, so these four patients were excluded while calculating “viral shredding time analysis”.	(Ke et al., 2020)
2	Open label controlled study/Allocated as per patients' choice	PCR+, Radiologically confirmed COVID-19 cases positive for the virus for >28 days despite standard of care.	Leflunomide 30 mg/day in patients <64 years and 20 mg/day in patients ≥65 years N = 15	Standard of care N = 12	Standard of care was given to both the groups, which included antibiotics, antivirals, glucocorticoids and Lianhua capsules	Rate and time of SARS-CoCV-2 clearance, 14 and 30 day hospital discharge rate, flare incidence, Adverse event	The trial was initiated and registered as RCT (ChiCTR2000030058), but later the allocation to different groups were made on the basis of patients' choice.	Wang et al. (2020b)
3	Case series	COVI-19 positive multiple sclerosis patients on teriflunomide	6 Patients already on Teriflunomide for multiple sclerosis with mean duration 2.1 ± 1.6 years.	N.A.	N.A.	All the 6 cases had mild self-limiting disease.	None had other co-morbidities, PCR diagnosis in only three cases, rest three diagnosis was done based on typical symptomatology following a contact.	(Mantero et al., 2020b, p. 19, p. 19)
4	Case series	Multiple sclerosis patients on teriflunomide developing COVID-19	5 patients already on teriflunomide for multiple sclerosis.	N.A.	N.A.	In all 5 patients, disease was mild disease.	Symptoms ranged from mild fever to mild dyspnea. In 4 patients, there was no requirement of hospitalization, while the 5th patient developed the disease during hospitalization.	Mantero et al. (2020b)