This study aims to evaluate the effect of l-carnitine as add- on therapy for improving the outcome in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that affects joints of hand, wrist and foot. Its epidemiology is more pronounced in female to male in ratio 3:1 . Etiology of the disease is related to genetics and environmental factors that lead to formation of epitopes initiating autoimmune response . It is characterized by symmetrical polyarthritis in equal or more than 5 joints and it is known that long term inflammation leads to bone deformities, cartilage damage and synovitis. signs and symptoms include pain and tenderness of joints, morning stiffness for more than 30 minutes, fever, fatigue and weight loss . Also, there are extra-articular manifestations like rheumatoid nodules , interstitial lung disease and ocular manifestations like scleritis . Many treatment approaches in RA are based on anti- inflammatory, anti-oxidant and immune suppressive drugs mainly DMARDs. Up till now, there is no anti-inflammatory agent that is both safe and effective equivalent to DMARDs which are first line of treatment and that can be a scientific gap that should be filled in future research prespectives.

L-Carnitine is a nutritional supplement that is used for enhancing performance in

exercises, valproic acid toxicity, Rett syndrome and in case of secondary carnitine deficiency like in end stage renal disease (ESRD). Physiologically, it is synthesized from lysine and methionine. It is involved in energy production by assisting in transportation of long chain fatty acid into the mitochondria where they undergo beta oxidation for ATP production. Several studies have successfully proven that it has antioxidant effect by activating PPAR gamma which is transcription factor that directly increases expression of antioxidant enzymes like super oxide dismutase (SOD) . LC also have anti-inflammatory effect by acting on PPAR gamma that also inhibits Nf-KB pathway, thus decreasing release of inflammatory mediators. That was mentioned in literature done on inflammatory diseases like coronary artery disease and sepsis . The need for an add on therapy in RA increases to improve response to treatment and provide cost effectiveness benefit that opens the door for repurposing trials.

Inclusion Criteria:

• age between 18-60 years old
• diagnosed of rheumatoid arthritis according to 2010 American College of Rheumatology/European League Against Rheumatism criteria for at least 6 months
• enrolled patients treated with one of more of conventional DMARDs for ≥ 6 months with stable dose for ≥ 1 month before start of the study
• active RA despite conventional DMARDs treatment (DAS28 ESR more than or equal 3.2)
• patient or legal representative should sign informed consent

Exclusion Criteria:

• pregnant or lactating female
• patients with liver dysfunction (>1.5x the upper limit of normal value for ALT & AST)
• Patients with kidney dysfunction (serum creatinine more than 1.2 mg/dl)
• Patients with any active infection or concurrent malignancy
• patients with uncontrolled medical conditions or other rheumatic diseases
• patients currently taking drugs that could interact with carnitine like: warfarin