Clinical study evaluating the efficacy and safety of Cilostazol as an adjuvant therapy to methotrexate on patients with rheumatoid arthritis.

Objective: This study aims to assess the safety as well as effectiveness of Cilostazol as a complementary therapy to methotrexate among individuals with active rheumatoid arthritis.

Method: This study was a randomly allocated, double-blind, placebo-controlled parallel design involving 70 patients who were diagnosed with active rheumatoid arthritis. Participants were randomly assigned to two sets: the control group (n = 35) which received methotrexate "MTX" (7.5 mg IM weekly) plus placebo tablets twice daily and the Cilostazol group (n = 35), which received the same MTX" dose plus Cilostazol 50 mg twice daily for 3 months. Patients were assessed to determine the serum levels of C-reactive protein (CRP) nuclear factor kappa B (NF-κB), hemoxygenase-1 (HO-1), and cyclic adenosine monophosphate (cAMP). Disease Activity Score (DAS28-CRP), Multidimensional Health Assessment Score (MDHAQ), and morning stiffness duration were also assessed.

Results: The Cilostazol group produced a significant improvement in cAMP level as compared to the control group (P = 0.001). cAMP level showed a significant inverse correlation with DAS28-CRP (r = -0.336; P = 0.004). However, Cilostazol group produced non-significant improvements in the serum levels of the other biological markers (CRP, NF-κB, and HO-1), DAS28-CRP score, MDHAQ score, and morning stiffness duration as compared to the control group (P > 0.05). The implication of Cilostazol for patients with rheumatoid arthritis was tolerable and safe.

Conclusion: The beneficial effect of Cilostazol on cAMP and the negative correlation between cAMP and DAS28-CRP could support its impact on the disease activity. Further research seems necessary to elucidate the mechanisms underlying the link between cAMP and disease activity.

Trial registration: Clinical Trials.gov identifier: NCT05594680, The date of registration is: 30/10/2022.