Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatological disorder in
childhood of unknown etiology and a major cause of functional disability. It has a prevalence
rate of about 1/1000 worldwide. The American College of Rheumatology (ACR) defines JIA as
inflammation in one or more joints of unknown etiology with onset prior to age 16 years and a
minimum of 6 weeks duration, following the exclusion of other known causes of synovitis. The
International League of Associations for Rheumatology criteria classifies JIA into several
different subgroups depending on the number of joints affected, presence of extra-articular
manifestations such as uveitis or glomerulonephritis, systemic symptoms, serology and genetic
factors. Peripheral arthritis is the common predominant clinical presentation among the
various types. The three main types of JIA are polyarticular, oligoarticular, and systemic
JIA. Therefore, diagnosis of JIA depends on physical findings, medical history, and the
exclusion of other diagnoses.
The main hallmark of JIA is joint inflammation with bone resorption and tissue destruction.
This chronic inflammation limits the daily activities and productivity of patients.
Interleukin-1 (IL-1), IL-6, IL-17, and tumor necrosis factor-α (TNF-α) are inflammatory
cytokines that play an important role in the pathogenesis, prognosis, disease activity, and
systemic features of JIA. Additionally, abnormal activation of T-cells, B-cells, natural
killer (NK) cells, dendritic cells (DC), macrophages and neutrophils contribute to the
pathogenesis of JIA.
All medications used to treat JIA including nonsteroidal anti-inflammatory drugs (NSAIDs),
corticosteroids, methotrexate, and biological agents have considerable adverse effects in
addition to the high cost of the biologics. Also, despite the success of these treatment
approaches, patients may still have active disease with other sequelae from chronic
inflammation and considerable morbidity that may negatively impact patients' quality of life.
Therefore, evaluating the potential benefit of alternative add-on anti-inflammatories and
antioxidants might be a promising area for further research.
Coenzyme Q10 (CoQ10) is a mitochondrial electron carrier and a powerful lipophilic
antioxidant located in almost all cell membranes and plasma lipoproteins. It can be found
naturally and acquired from the diet or synthesized in-vivo by all cells of the body. Various
in-vitro and animal studies have demonstrated the antioxidant and anti-inflammatory effect of
CoQ10.7 This has raised interest in its therapeutic potential against pathologies related to
mitochondrial dysfunction and enhanced oxidative stress such as systemic autoimmune diseases.
Several preclinical studies in animal models as well as clinical trials in patients with
rheumatoid arthritis (RA) have demonstrated the beneficial effects of CoQ10. Results show
that CoQ10 can reduce the oxidative and inflammatory status as well as clinical features that
characterize this systemic autoimmune disease.
In an attempt to understand the mechanisms by which CoQ10 exerts its anti-inflammatory and
immunomodulatory effect, Jhun et al conducted two studies on induced-arthritis mice models.
Their results showed that the mice that received CoQ10 showed significant decrease in RA
severity. Immunohistochemical analysis of synovial tissue showed that CoQ10 administration
lead to significantly lower levels of proinflammatory cytokines such as IL-21, IL-1, IL-6,
IL-17, TNF-α and vascular endothelial growth factor (VEGF). Also, oxidative stress markers
including nitrotyrosine and inducible nitric oxide synthase (iNOS) expression were
significantly reduced in mice treated with CoQ10. CoQ10 also exhibited immunomodulatory
effects on B and T-cells, such as down-regulating IL-17 expression and Th17 cells population
induced by inflammatory response.
Furthermore Bauerova et al. exhibited that the addition of CoQ10 to methotrexate (MTX), the
most commonly prescribed anti-rheumatic agent, suppressed the progression of RA in rats more
than MTX alone. The effect on oxidative stress and immunomodulation was shown through a
decrease in the plasma levels of MDA and IL-1, respectively.10 CoQ10 also proved that it has
a protective role against hepatotoxicity caused by methotrexate. This effect was shown in a
study by Tawfik et al. where liver function enzymes improved after the combination of CoQ10
with MTX in rats.
To further elucidate the effect of CoQ10 supplementation, two randomized clinical trials
tested its use in adult rheumatoid arthritis patients. Abdollahzad et al. focused on the
effect of CoQ10 on oxidative stress and inflammatory markers. They registered a significant
decrease in serum levels of MDA & TNF-α, and trending decrease in IL-6. Moreover, no adverse
drug events were observed confirming the safety and tolerability of CoQ10. With more focus on
disease activity, Nachvak et al reported significant decrease in Disease Activity Scores
(DAS-28), swollen joint count, tender joint count, and the visual analogue scale (VAS) scores
accompanied by a reduction in erythrocyte sedimentation rate (ESR) and matrix
metalloproteinase (MMP-3) levels.
Altogether, evidence supports the beneficial effect of CoQ10 supplementation not only on
inflammatory markers and oxidative stress but also on clinical features and presentation of
arthritis patients. Also, CoQ10 has been used in doses up to 20 mg/kg/day in children safely
and was well tolerated. Up to date, there is no published study to evaluate the use of CoQ10
in JIA. Thus, the investigators would like to evaluate the effect of CoQ10 oral
supplementation as adjuvant therapy on the clinical outcomes in pediatric JIA patients.
A prospective, randomized, controlled, single blind clinical trial will be conducted on 60
Juvenile Idiopathic Arthritis (JIA) patients at the Pediatric Allergy, Immunology,
Rheumatology Clinic, Children's Hospital, Ain Shams University.
At baseline, caregivers of patients who are eligible will be educated about the study
protocol and will be required to sign a written informed consent before enrollment in the
study.
Sixty patients will be recruited in the study and will be randomized to one of the following
groups:
A) Intervention (Coezyme Q10) Group (30 patients): will receive their JIA standard treatment
plus 100 mg Coenzyme Q10 capsules daily for 3 months.
B) Control Group (30 patients): will receive their standard JIA treatment plus placebo
Blood samples will be withdrawn from patients at baseline and at the end of the 3 months
trial period. After 3 months of CoQ10 supplementation, all the outcomes will be reassessed
and reported to determine the effect on CoQ10 supplementation.