A randomized controlled interventional study to evaluate the efficacy and safety of nicotinamide supplementation in rheumatoid arthritis patients receiving conventional synthetic disease modifying anti-rheumatic drugs.

Study design:

A prospective randomized controlled interventional parallel open label study.

Patient randomization:

All patients fulfilling the inclusion criteria will be randomly assigned by simple randomization into either nicotinamide group or control group as follows:

• Nicotinamide group: consists of thirty-five patients who will receive nicotinamide 1000mg tablet once daily.in addition to their conventional therapy.
• Control group: consists of thirty-five patients who will receive their conventional therapy only.

Methodology:

At baseline, the following will be obtained through patients' interview:

1. Demographic data.
2. Medical history and comorbidities.
3. The disease activity; identified through patients' physical examination and serum C-Reactive Protein (CRP) levels as prerequisites for Disease Activity Score-28 (DAS-28-CRP).
4. The disease duration.
5. Current medications history.

Evaluation of the efficacy and safety of nicotinamide will be assessed at baseline and after three months through:

1. Blood sampling will be collected from patients for serum CRP , Erythrocyte sedimentation rate (ESR) and analysis of Interleukin-10 .These samples will be directly centrifuged at 1000 x g for fifteen minutes and then plasma will be separated and collected in capped test tubes, then will be stored at -80 °C until analysis.

   Interleukin-10 serum level will be measured using an Enzyme Linked Immunosorbent Assay (ELISA) technique.

2. Disease Activity will be calculated based on tender joint count (TJC) and swollen joint count (SJC) following the assessment of twenty-eight joints, serum CRP level, and the patient's global health assessment (PGA) on a scale from zero to one hundred. The score will be calculated using the following equation:

   DAS-28-CRP = 0.56* √(TJC28) + 0.28* √(SJC28) + 0.36*ln (CRP + 1) +0.014*(PGA) + 0.96

3. Patient's QOL will be assessed by using the Health Assessment Questionnaire-Disability Index (HAQ-DI)

4. Patients will be educated about the side effects and/or adverse effects of nicotinamide, where, safety and tolerability will be monitored by reporting the incidence of any side effect and /or adverse effect such as stomach upset, flatulence, dizziness, headache, and rash.

Blood samples will be collected for complete blood count (CBC), alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (Scr.) levels analysis to monitor adverse effects of conventional synthetic disease-modified antirheumatic (csDMARDs) drugs and nicotinamide.

Inclusion Criteria:

• Adult patients (18-65 years).
• Patients with a diagnosis of established rheumatoid arthritis.
• Patients presenting with moderate to high disease activity identified as disease activity score-28 based on C-reactive protein levels (DAS-28-CRP) >3.2.
• Receiving stable regimen of one or more conventional disease modifying antirheumatic drugs for at least the past three months.
• Patients willing to sign an informed consent.

Exclusion Criteria:

• Patients with a known history of hypersensitivity or drug allergies to nicotinamide
• Patients receiving nicotinamide for any other indications.
• Receiving any dosage forms/ dosage regimen of vitamin B3 supplementation
• Receiving biologic disease modified antirheumatic drugs therapy.
• Impaired liver functions (liver transaminases level ≥ three times upper normal limits).
• Impaired kidney functions (estimated glomerular filtration rate (eGFR) < 30 ml/min)
• Pregnancy and lactation.
• Patients with other auto-immune diseases.