Cost-Utility Analysis of TNF-α Inhibitors, B Cell Inhibitors, and JAK Inhibitors Versus csDMARDs for Rheumatoid Arthritis Treatment.

INTRODUCTION: Rheumatoid arthritis (RA) is a progressive and debilitating disease, causing persistent joint pain that limits daily activities requiring long-term treatment. Newer targeted therapies expand RA treatment options, but their high cost necessitates a focus on cost effectiveness. To address this, we aim to conduct a cost-utility analysis of these newer RA pharmacotherapies to support evidence-based policy decision-making. METHODS: We analyzed the cost-utility of sequential treatment with TNF-α, B cell and JAK-inhibitors compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for RA treatment in methotrexate (MTX) nonresponders. We used a Markov model with lifetime horizon and 6-month cycles from an Indian health system perspective. Costs (INR 2022) and quality-adjusted life years (QALYs) were used to determine the incremental cost-effectiveness ratios (ICERs) at a cost-effectiveness threshold of India's gross domestic product (GDP) per capita (2022). We assessed uncertainty using univariate, probabilistic sensitivity, and scenario analyses. RESULTS: Despite additional QALYs, TNF-α, B cell, and JAK inhibitors were not cost-effective for treating moderate-to-severe patients with RA unresponsive to csDMARDs (including MTX) in India, as increased costs outweighed their clinical benefits. ICERs ranged from 10,46,206 to 31,09,207 Indian Rupees in the base case analysis, exceeding three times India's GDP per-capita [approximately USD $13,287 to $39,487 and GBP £10,776 to £32,025]. Sensitivity analyses confirmed the results' robustness. Scenario analysis suggested that a cost reduction of over 75% in drug prices could make most of the interventions cost effective compared with csDMARDs. CONCLUSIONS: TNF-α, B cell, and JAK-inhibitors are not cost-effective compared with csDMARDs for patients with RA who have not responded to MTX in India at the current prices. Cost-effectiveness estimates were highly influenced by drug pricing variations. Therefore, reducing the prices of these interventions could enhance affordability, potentially leading to their inclusion in publicly funded health programs.

Household catastrophic health expenditures for rheumatoid arthritis: a single centre study from South India.

Rheumatoid arthritis (RA) not only has a physical and emotional toll but also has a substantial economic impact. This study aims to estimate the burden of catastrophic health expenditure (CHE) on households due to RA in Tamil Nadu, India. We conducted cross-sectional descriptive hospital-based single-centre study at a tertiary care private multispecialty hospital in Tamil Nadu, India. The study comprised 320 RA patients who visited the outpatient clinic from April to October 2022. Demographic and baseline descriptive characteristics were reported. Multivariable logistic regression analyses were performed to identify major determinants associated with CHE. We also examined the inequality in household annual income and CHE. Most study participants were females (88.1%) with a mean age (SD) of 55.57 ± 12.29 years. About 93% of RA patients were from urban areas, and 89.4% were literate. Only 8.1% of respondents reported having health insurance. Households experiencing CHE owing to RA were 51.4% (n = 162). The mean (95% CI) annual health expenditure for treating RA is ₹44,700 (₹41,710 to 47,690) with a median (IQR) of ₹39,210 (₹25,500) [$476 ($310)]. The corresponding mean (95% CI) and median (IQR) Out of pocket expenditure among RA patients per household were ₹40,698 (₹38,249 to 43,148) [$494 ($464 to $524)] and ₹36,450 (23,070) [$442 ($280)] respectively. Nearly half of the households with RA patients had a financial catastrophe due to healthcare costs being paid out-of-pocket and limited health insurance coverage. The results underscore the need for comprehensive approaches to strengthening public health policies along with financial risk protection and quality care in India.

Cost-effectiveness of janus kinase inhibitors for rheumatoid arthritis: A systematic review and meta-analysis of cost-utility studies.

Introduction: Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports. Methods: Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger's test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented. Results: We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95% CI, 1,635 to 38,137) but with considerable heterogeneity (I2 = 99.14). As a second-line treatment for csDMARD failed RA, JAK-i is cost-effective than csDMARD/bDMARD with a pooled INB of $23,144 (74.1-46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp $26,157 (-7,284 to 59,598). Conclusion: Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD42021222541.

Adipokine interactions promote the pathogenesis of systemic lupus erythematosus.

BACKGROUND: Adipokines are chemical mediators released from adipose tissue involved in regulation of appetite, insulin sensitivity, immune system and inflammatory responses. Adipokines contributes to low grade inflammatory response in autoimmune disease like Systemic Lupus Erythematosus (SLE) but the pathophysiology is yet not clear. The aim of this study is to understand role of adipokine interactions in SLE disease pathogenesis. METHODS: Sixty newly diagnosed treatment naïve SLE patients fulfilling the ACR criteria and forty age-sex matched healthy subjects were enrolled in thiscase-control study. Disease activity in SLE patients was evaluated using SELENA-SLEDAI. Array of adipokines, C1q circulating immune complexes (C1q-CIC), anti-C1q, anti-ribososmal P0 (anti-RibP0) and anti-mitochondrial antibodies (AMA) levels were detected by ELISA. Antinuclear antibodies (ANA) and anti-dsDNA autoantibodieswere detected by Indirect Immunofluorescence (IIF), while antigen specificities were detected by Immunoassay blot. Serum levels of C3 and C4 complement factors were assessed by nephlometer. RESULTS: Statistically significant elevation in progranulin, adipsin and resistin levels was seen among SLE patients when compared to healthy controls (p < 0.0001). Leptin and omentin levels were significantly reduced in SLE patients (p < 0.0001). There was no statistically significant difference in serum adiponectin, chemerin and visfatin levels when these two groups were compared (p > 0.05). Adiponectin, adipsin and resistin levels were elevated in SLE patients with renal manifestations (p < 0.05). Reduced leptin levels were significantly associated with presence of renal manifestations (p < 0.05). Adiponectin levels positively correlated with disease activity (r = 0.294, p = 0.027) whereas negatively correlated with C3 levels (r = -0.439, p = 0.0007). A positive correlation was observed between hypocomplementemia and leptin levels (p < 0.05). Leptin levels were negatively correlated with disease activity, anti-dsDNA, C1q-CIC and anti-C1q levels (p < 0.05). A significant positive correlation was observed between progranulin levels and anti-ribosomal P0 antibodies (r = 0.499, p < 0.0001). CONCLUSION: Adipokines levels and associated clinical manifestations suggest involvement of adipokines in disease pathogenesis of SLE. SLE disease activity and complement components may suggest regulatory effect of adipokines (adiponectin and leptin) on disease pathogenesis. Further studies on adipokines in SLE patients with renal manifestations may propose them as prognostic markers in renal damage. TRIAL REGISTRATION: NA.

State of knowledge of coastal and marine biodiversity of Indian Ocean countries.

The Indian Ocean (IO) extends over 30% of the global ocean area and is rimmed by 36 littoral and 11 hinterland nations sustaining about 30% of the world's population. The landlocked character of the ocean along its northern boundary and the resultant seasonally reversing wind and sea surface circulation patterns are features unique to the IO. The IO also accounts for 30% of the global coral reef cover, 40,000 km² of mangroves,some of the world's largest estuaries, and 9 large marine ecosystems. Numerous expeditions and institutional efforts in the last two centuries have contributed greatly to our knowledge of coastal and marine biodiversity within the IO. The current inventory, as seen from the Ocean Biogeographic Information System, stands at 34,989 species, but the status of knowledge is not uniform among countries. Lack of human, institutional, and technical capabilities in some IO countries is the main cause for the heterogeneous level of growth in our understanding of the biodiversity of the IO. The gaps in knowledge extend to several smaller taxa and to large parts of the shelf and deep-sea ecosystems, including seamounts. Habitat loss, uncontrolled developmental activities in the coastal zone, over extraction of resources, and coastal pollution are serious constraints on maintenance of highly diverse biota, especially in countries like those of the IO, where environmental regulations are weak.