Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract Background: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. Methods: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. Results: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI − 5.58, 5.82), BMI 0.08 kg/m2 (95% CI − 1.76, 1.92), FM − 0.08 kg (95% IC − 5.31, 5.14), and FFM − 2.08 kg (95% CI − 7.37, 3.21). Conclusion: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. Trial registration: PROSPERO code: CRD42020206949.

Effects of disease modifying antirheumatic drugs on lipid profile in patients with rheumatoid arthritis / 中国免疫学杂志

RA has been associated with a significantly increased risk of coronary heart disease compare to the general population because of dyslipidemia.Anti-rheumatic drugs have various effects on lipid profile,which in part appear pro-atherogenic.The aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid profil,so the cardiovascular safety for antirheumatic drugs would be valuable.

Cost-Minimization Analysis of Biologic Disease-Modifying Antirheumatic Drugs Administered by Subcutaneous Injections in Patients with Rheumatoid Arthritis

BACKGROUND: The subcutaneous formulation of biologic disease-modifying antirheumatic drugs (DMARDs) was preferred due to favored self-administration and would be an economical treatment option for patients with rheumatoid arthritis. This study was to compare the economic impact of biologic DMARDs administered by subcutaneous injection in patients with rheumatoid arthritis who had inadequate response to conventional DMARDs. METHODS: The cost-minimization analysis was conducted to estimate the lifetime health care costs of treatment sequences with subcutaneous biologic DMARDs as first-line therapy from a health care system perspective. The Markov model was developed to represent the transitions through treatment sequences based on American College of Rheumatology response rate and discontinuation rate. The health care costs comprised the cost of medications, administration, dispensing, outpatient visits, test/diagnostic examination, palliative therapy and treatment of serious infection. All costs were expressed in 2016 Korean Won (KRW) and discounted at 5%. RESULTS: The mean lifetime health care cost per patient was lowest in the etanercept sequence, which was estimated at KRW 63,441,679. The incremental costs of the treatment sequence started with adalimumab, golimumab, abatacept, and tocilizumab were KRW 7,985,730, KRW 4,064,669, KRW 2,869,947, and KRW 4,282,833, respectively, relative to etanercept sequence. These differences in costs mainly were attributable to medication costs. One-way and probabilistic sensitivity analyses confirmed that etanercept represented the option with the lowest cost compared with comparators. CONCLUSION: This study found that etanercept is likely a cost-saving treatment option among subcutaneous biologic DMARDs in patients with rheumatoid arthritis.

Comparative Effectiveness of Biologic DMARDs in Rheumatoid Arthritis Patients with Inadequate Response to conventional DMARDs: Using a Bayesian Network Meta-analysis

BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with insufficient response or intolerance to conventional DMARDs (cDMARDs). These agents have considerable efficacy compared with conventional DMARDs, but only a few head-to-head comparisons among these agents have been performed. The objective of this systematic review and network meta-analysis (NMA) was to compare the relative efficacy of Certolizumab with conventional DMARD to licensed bDMARD with cDMARD therapy for patients who failed to prior cDMARD treatment under the condition of the reimbursement coverage criteria in Korea. METHODS: A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 at six months. Bayesian outcomes were calculated as median of treatment effect, probability of the best, Odds Ratio (OR) and probability that OR was greater than one. RESULTS: Compared with other bDMARDs, Certolizumab were associated with higher or comparable ACR response rates; in ACR20, the OR (probability of OR>1) was 2.08 (92.6%) for Adalimumab, 1.86 (85.7%) for Etanercept, 1.89 (79.5%) for Golimumab, 2.36 (92.1%) for Infliximab, 1.79 (87.0%) for Abatacept, 1.74 (80.8%) for Rituximab and 1.82 (86.8%) for Tocilizaumab. In ACR50 and ACR70, the ORs did not present significant differences. CONCLUSION: Certolizaumab with cDMARD was more effective or comparable than other bDMARDs in patients who failed prior cDMARD treatment.

Treatment of juvenile rheumatoid arthritis / 소아과

The systematic approach to pharmacologic treatment is typically to begin with the safest, simplest, and most conservative measures. It has been realized that the more rapidly inflammation is under control, the less likely it is that there will be permanent sequelae. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of initial treatment for inflammation. In addition, the slow-acting antirheumatic drugs (SAARDs) and disease-modifying antirheumatic drugs (DMARDs) have efficacy of anti-inflammatory action in children with chronic arthritis. New therapeutic modalities for inflammation, such as etanercept and infliximab, promise even further improvements in the risk/benefit ratio of treatment. It is not typically possible at the onset of the disease to predict which children will recover and which will go on to have unremitting disease with lingering disability or enter adulthood with serious functional impairment. Therefore, the initial therapeutic approach must be vigorous in all children.

Medical Therapy for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis and damage of bone and cartilage. The major goals of therapy in RA are to relieve pain, swelling of joints; improve joint function; stop joint damage, and prevent disability and disease-related morbidity. The past decade has seen a major transformation in the treatment of RA in terms of approach and choice of drugs. The previous therapeutic approach, termed the therapeutic pyramid, penerally involved initial conservative management with non-steroidal anti-inflammatory drugs (NSAIDs) for several years; disease-modifying antirheumatic drugs (DMARDs) were withheld until clear evidence of erosions was seen. DMARDs were then added individually in slow succession as the disease progressed. This form of treatment has been supplanted by early initiation of DMARDs and combination DMARD therapy in patients with the potential for progressive disease. The idea of early intervention with DMARDs has been validated in several randomised trials. This paradigm shift partly resulted from unsatisfactory outcomes with the pyramid approach, and an increased awareness of the cost, lost productivity, morbidity, and decreased life expectancy associated with RA. These findings are the consequences of progressive disease, and have provided the impetus for development of more effective therapies to prevent joint destruction and maintain functional status. The continuing elucidation of pathophysiological pathways relevant in RA, coupled with advanced in biotechnology, offer substantial hopes for the development of potent and specific pharmacotherapy for RA.