Pharmacogenetics of Leflunomide in the Management of Rheumatoid Arthritis

NCT07388407 | Recruiting FDA Drug

• 1 other identifier: FUMCRCT3
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 2

Brief Summary

1. 1.Patients taking leflunomide as the only disease-modifying anti-rheumatic drug (DMARD) will be recruited after consent.
2. 2.Blood sample for DNA extraction will be taken The patient will be followed up till two visits 3 months apart, and efficacy and toxicity will be checked using DAS28, ultrasonography, and blood tests for ESR, CRP, anti-CCP, liver function tests, etc. The data form for toxicity will be filled.
3. 3.DNA will be extracted in the laboratory, and SNP will be identified.
4. 4.The efficacy and toxicity data will be studied against the SNPs found
5. 5.An algorithm will be constructed for Pakistani RA patients taking leflunomide.

Conditions

Rhematoid Arthritis

Keywords

RA; SNP; Leflunomide

Outcome Measures

Primary Outcomes (1)

• DAS Score Measurement

  The Disease Activity Score (DAS28) is calculated by assessing 28 tender/swollen joints, blood inflammatory markers (ESR or CRP), and patient global health (VAS), with scores \<2.6 indicating remission and \>5.1 indicating high disease activity. It is primarily computed using specialised calculators for Rheumatoid Arthritis. We will take this score at the start of leflunomide therapy, at three-month intervals and at 6 months. The significant outcome will be a 10% decrease from the baseline and will be correlated with the SNP identified.

  2 years

Secondary Outcomes (2)

• SNP identification in DHOD gene

  2 years

• Measurement of Hepatotoxicity of Leflunomide

  2 years

Study Arms (1)

RA patients taking Leflunomide

RA patients in Pakistani population taking Leflunomide as a single DMARD

Drug: Study for the correlation of SNPs with efficacy and toxicity of Leflunomide in RA patients

Interventions

Study for the correlation of SNPs with efficacy and toxicity of Leflunomide in RA patients DRUG

Study for the correlation of SNPs with efficacy and toxicity of Leflunomide in RA patients

RA patients taking Leflunomide

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient of RA taking Leflunomide

You may qualify if:

• At baseline, all patients should fulfill the revised ACR/EULAR criteria for RA10
• Pakistani individuals
• between ages of 20-75 years
• New cases started on Leflunomide/ those already taking for less than a month and their biochemical and clinical data is available

You may not qualify if:

• Patients not willing to participate/ consent not given
• Patients below the age of 20
• Non- Pakistani origin
• Taking another DMARD simultaneously
• Compromised renal and hepatic functions
• Cognitive impairment, neurological disease
• Pregnant/ lactating patients
• Patients having inflammatory bowel disease/ Irritable bowel syndrome
• Patients with active infective diseases -Patients who fail to complete 3 months of leflunomide therapy-

Sponsors & Collaborators

• Shifa Tameer-e-Millat University: collaborator
• Foundation University Islamabad: lead

Study Sites (2)

Shifa International Hospital

Islamabad, Punjab Province, 44000, Pakistan

COMPLETED

Fauji Foundation Hospital, Rawalpindi

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

Related Publications (12)

• The association of DHODH, CYP1A2, and ABCG2 gene polymorphism on efficacy and toxicity of leflunomide in the management of rheumatoid arthritis concentrations is associated with leflunomide cessation in rheumatoid arthritis. British Journal of Clinical Pharmacology, 81, 113-123.

  BACKGROUND

• HOPKINS, A. M., WIESE, M. D., PROUDMAN, S. M., O'DOHERTY, C. E., UPTON, R. N. & FOSTER, D. J. R. 2016. Genetic polymorphism of CYP1A2 but not total or free teriflunomide 17

  BACKGROUND

• HOCK, E. S., MARTYN-ST JAMES, M., WAILOO, A., SCOTT, D. L., STEVENSON, M., RAWDIN, A., SIMPSON, E. L., DRACUP, N. & YOUNG, A. 2021. Treat-to-Target Strategies in Rheumatoid Arthritis: a Systematic Review and Cost-Effectiveness Analysis. SN Comprehensive Clinical Medicine, 3, 838-854.

  BACKGROUND

• GRABAR, P. B., ROZMAN, B., LOGAR, D., PRAPROTNIK, S. & DOLŽAN, V. 2009. Dihydroorotate dehydrogenase polymorphism influences the toxicity of leflunomide treatment in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases, 68, 1367-1368.

  BACKGROUND

• FLEISS, J. L., LEVIN, B. & PAIK, M. C. 2013. Statistical Methods for Rates and Proportions, Wiley. GAUTHIER, M. 2007. Simulation of polymer translocation through small channels: A molecular dynamics study and a new Monte Carlo approach.

  BACKGROUND

• DEVARBHAVI, H., GHABRIL, M., BARNHART, H., PATIL, M., RAJ, S., GU, J., CHALASANI, N. & BONKOVSKY, H. L. 2022. Leflunomide-induced liver injury: Differences in characteristics and outcomes in Indian and US registries. Liver Int, 42, 1323-1329.

  BACKGROUND

• DAVILA, L. & RANGANATHAN, P. 2011. Pharmacogenetics: implications for therapy in rheumatic diseases. Nature Reviews Rheumatology, 7, 537-550.

  BACKGROUND

• BOHANEC GRABAR, P., ROZMAN, B., TOMŠIČ, M., ŠUPUT, D., LOGAR, D. & DOLŽAN, V. 2008. Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients. European Journal of Clinical Pharmacology, 64, 871 876.

  BACKGROUND

• BOHANEC GRABAR, P., GRABNAR, I., ROZMAN, B., LOGAR, D., TOMSIC, M., SUPUT, D., TRDAN, T., PETERLIN MASIC, L., MRHAR, A. & DOLZAN, V. 2009. Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2-Cyano-3-hydroxy-N-[4 (trifluoromethyl)phenyl]-2-butenamide (A77 1726) pharmacokinetics in leflunomide treated patients with rheumatoid arthritis. Drug Metab Dispos, 37, 2061-8.

  BACKGROUND

• ASLAM MM, J. F., JOHN P, FAN K-H, BHATTI A, FEINGOLD E, ET AL. 2020. A sequencing study of CTLA4 in Pakistani rheumatoid arthritis cases. PLoS ONE, 15, e 0239426. BABIKER-MOHAMED, M. H., BHANDARI, S. & RANGANATHAN, P. 2024. Pharmacogenetics of therapies in rheumatoid arthritis: An update. Best Practice & Research Clinical Rheumatology, 101974.

  BACKGROUND

• ALMUTAIRI, K., NOSSENT, J., PREEN, D., KEEN, H. & INDERJEETH, C. 2021. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatology International, 41, 863-877.

  BACKGROUND

• ALETAHA, D., NEOGI, T., SILMAN, A. J., FUNOVITS, J., FELSON, D. T., BINGHAM, C. O., 3RD, BIRNBAUM, N. S., BURMESTER, G. R., BYKERK, V. P., COHEN, M. D., COMBE, B., COSTENBADER, K. H., DOUGADOS, M., EMERY, P., FERRACCIOLI, G., HAZES, J. M., HOBBS, K., HUIZINGA, T. W., KAVANAUGH, A., KAY, J., KVIEN, T. K., LAING, T., MEASE, P., MÉNARD, H. A., MORELAND, L. W., NADEN, R. L., PINCUS, T., SMOLEN, J. S., STANISLAWSKA-BIERNAT, E., SYMMONS, D., TAK, P. P., UPCHURCH, K. S., VENCOVSKÝ, J., WOLFE, F. & HAWKER, G. 2010. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum, 62, 2569-81.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

5ml blood after recruitment of subjects

Study Officials

• Prof Muzammil Hassan Najmi

  Foundation University Islamabad

  STUDY DIRECTOR

Central Study Contacts

Dr. Zarafshan Bader, MPhil, MBBS

CONTACT

0923005177254; zarafshan.bader@fui.edu.pk

Dr Abida Shaheen, PHD, MBBS, FAIMER FELLOW

CONTACT

abida.scm@stmu.edu.pk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2026
• First Posted: February 5, 2026
• Study Start: September 1, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

PA (2)