Abstract

Cyclophosphamide in a cohort of biologic naïve rheumatoid arthritis patients resistant to conventional DMARDs

Author(s): Howaida E Mansour, Khaled F Elhassanein, Maha A El Serwy, Marwa A Nassef, Asmaa M Abdallah & Noran O El-Azizi

Background: Rheumatoid Arthritis (RA) poses a significant economic burden in health services worldwide. The most important factor influences poor outcome in RA patients is the lack of drug adherence that is mainly due to financial cost and poor patient education. There is a significant number of RA patients fail to respond or show poor response to conventional DMARDs and they can’t afford the high cost of biologic therapy. Cyclophosphamide (CYC) is an immunosuppressive drug that inhibit the actively dividing inflammatory cells, suppressing the inflammatory cytokines and stops inflammation induced joint erosions in RA patients. To evaluate the efficacy of IV pulse methylprednisolone (MP) and Cyclophosphamide (CYC) in induction of remission in a cohort biologic naïve aggressive RA patients resistant to different combinations of conventional Disease-Modifying Anti Rheumatic Drugs (DMARDs). Methods and Findings: A prospective observational study performed on 30 RA patients diagnosed according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, who fail to respond to different combinations of conventional DMARDs for at least two years. All patients subjected to history taking, rheumatological examination, assessment of RA disease activity, laboratory investigations; Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide antibody (ACCP) recorded at baseline and after 6 months (study endpoint). All RA patients have been treated with monthly IV pulse 1 g MP and CYC at a dose 500 mg/m² surface area for 6 months. On comparing baseline to endpoint data there was a significant reduction in all disease activity parameters: number of tender and swollen joints, disease activity scores 28 (DAS28), Health Assessment Questionnaire (HAQ), Visual Analog Scale (VAS), ESR, CRP and platelet (PLT) level, with increase in haemoglobin in all treated patients at the study endpoint. No significant difference between RF, ACCP seropositivity and different disease activity markers, except for increased haemoglobin in RF positive and reduction of PLT count in positive ACCP patients’ post-treatment. High CRP at baseline indicates poor prognosis, response to pulse CYC therapy and high VAS at the study endpoint. Conclusions: Pulse MP and CYC monthly for 6 months significantly benefit in induction of remission in a biologic naïve aggressive RA patients resistant to different combinations of conventional DMARDs.