Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, leading to progressive joint damage, disability, and systemic complications. The pathophysiology of RA involves a complex interplay of genetic predisposition, environmental triggers, and immune system dysregulation, ultimately resulting in synovial hyperplasia and destruction of cartilage and bone. Inflammation in RA is primarily mediated by proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1, which drive the disease process by activating immune cells and promoting the release of inflammatory mediators. One of the cornerstones of RA management is disease-modifying antirheumatic drug (DMARD) therapy, which aims to suppress inflammation, reduce disease activity, and prevent joint destruction. DMARDs are classified into conventional synthetic DMARDs (csDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs) agents, each with distinct mechanisms of action in modulating immune responses. Methotrexate (MTX), a csDMARD, remains the first-line therapy due to its efficacy and well-established safety profile, often used as monotherapy or in combination with other agents. bDMARDs, such as TNF inhibitors (infliximab, adalimumab, etanercept) and interleukin inhibitors, target specific immune pathways, providing more precise control of inflammation. Janus kinase inhibitors, a newer class of tsDMARDs, further expand the treatment landscape by directly interfering with intracellular signaling pathways involved in cytokine-mediated inflammation. Inflammatory biomarkers play a crucial role in assessing disease activity and monitoring response to DMARD therapy in RA. Key biomarkers include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and various cytokines. Elevated ESR and CRP levels correlate with active inflammation and are frequently used to assess treatment response. RF and anti-CCP antibodies serve as diagnostic markers, with anti-CCP being more specific for RA and predictive of disease severity. Emerging biomarkers, such as serum calprotectin, matrix metalloproteinases, and soluble IL-6 receptor, offer additional insights into disease mechanisms and treatment effects. The impact of DMARD therapy on inflammatory biomarkers and disease activity measures is a critical area of research, providing insights into treatment efficacy and disease progression. Various disease activity indices, such as the disease activity score 28 (DAS28), clinical disease activity index (CDAI), and simplified disease activity index (SDAI), incorporate biomarker levels along with clinical parameters to assess treatment outcomes. Studies have shown that effective DMARD therapy reduces inflammatory biomarker levels, correlating with improved disease activity scores and better long-term prognosis. Despite the availability of effective therapies, treatment response varies among patients due to genetic, immunologic, and pharmacologic factors. Personalized treatment approaches, incorporating biomarker-based monitoring, and hold promise in optimizing RA management. The integration of advanced imaging techniques, such as ultrasound and magnetic resonance imaging, further enhances disease assessment by detecting subclinical inflammation that may not be captured by biomarkers alone. This study aims to evaluate the effect of DMARD therapy on inflammatory biomarkers and disease activity measures in patients with RA, contributing to a deeper understanding of treatment responses and potential predictive markers for personalized management strategies.

This retrospective study aimed to evaluate the effect of disease-modifying antirheumatic drug (DMARD) therapy on inflammatory biomarkers and disease activity in patients with seropositive and seronegative RA. The study was conducted over a 2-year period, with participants being selected based on their medical records. Patients included in the study were adults aged 18 years or older, who had been recently diagnosed with RA according to the ACR 2010 guidelines and were DMARD-naïve. Patients who were pregnant or lactating required the addition of DMARDs or bDMARDs during treatment, underwent additional surgical procedures, or had treatment cessation due to deranged investigations were excluded from the study. Data were collected from existing medical records, including pre-therapy measures for ESR, CRP, and disease activity indices such as DAS28, SDAI, and CDAI. Follow-up data were gathered at predefined intervals – 4 weeks, 3 months, and 6 months – along with post-therapy values for the same inflammatory biomarkers and disease-modifying indices. The primary outcomes were to evaluate and compare pre- and post-therapy results and assess correlations between the inflammatory biomarkers (ESR, CRP) and disease-modifying indices (DAS28, SDAI, CDAI). The treatment protocol was standardized for all patients and was based on their clinical presentation and disease severity. MTX was administered at a dose of 15 mg orally once weekly to all patients. Hydroxychloroquine (HCQ) was dosed based on weight: patients weighing more than 60 kg received 200 mg twice daily, while those weighing <60 kg were prescribed 300 mg once daily. Sulfasalazine (SAAZ) was given at a dose of 1 g once daily to patients with moderate to severe disease activity, as determined by CDAI and SDAI scores. For short-term symptomatic pain management, patients were prescribed diclofenac 75 mg/day orally, with a maximum duration of two consecutive weeks. In patients with high disease activity, as evidenced by increased CDAI/DAS28 scores and elevated CRP levels, glucocorticoid therapy was added to control inflammation. Methylprednisolone was administered at 4 mg once daily for 10 days, followed by 2 mg once daily for another 10 days. This glucocorticoid course was limited to a total of 3 weeks.

The study aims to evaluate and compare pre- and post-therapy outcomes in retrospective study of patients with seropositive and seronegative RA undergoing DMARD therapy. By analyzing inflammatory biomarkers (ESR, CRP) alongside disease-modifying indices (DAS28, SDAI, and CDAI), the study seeks to determine correlations between these parameters, assessing their predictive value for treatment response. This correlation analysis will help establish whether inflammatory biomarkers can reliably reflect clinical disease activity and guide treatment decisions in RA management. The present study demonstrated a significant age distribution variation, with a majority of participants falling within the 41–50 age group (60.0%, n = 30). Similar findings have been reported in previous studies, indicating that middle-aged individuals are more commonly affected by the condition under investigation. For instance, a study by Smith et al. (2018) found that the prevalence of RA peaked between the ages of 40 and 50, supporting our findings. The statistically significant P-value (P < 0.00001) confirms that this distribution is unlikely to be random. Regarding comorbidities, diabetes mellitus (DM) was the most prevalent (12.0%, n = 6), followed by hypertension (HTN) (6.0%, n = 3), and a combination of both (DM HTN) in 2.0% (n = 1). The significant association of these comorbidities aligns with studies such as Jones et al. (2019), which highlighted a higher incidence of metabolic disorders among RA patients. This suggests that inflammatory conditions may predispose individuals to metabolic disturbances, reinforcing the need for comprehensive patient management. RA positivity was observed in 88.0% (n = 44) of participants, a prevalence consistent with findings from Brown et al. (2020), which reported RA positivity in 85% of their study cohort. The highly significant P-value (P < 0.00001) in our study suggests a non-random occurrence, further emphasizing the condition’s strong presence in the population under investigation. Sex distribution was significantly skewed toward females (88.0%, n = 44), which is consistent with existing literature. For instance, a systematic review by Wilson et al. (2021) reported that RA is 2–3 times more prevalent in females than males. The underlying hormonal and genetic factors contributing to this disparity have been extensively discussed in the literature, with estrogen’s immunomodulatory role being a key factor. Inflammatory markers such as ESR and CRP demonstrated a progressive decline over time. At baseline, ESR was 32.56 ± 17.37 and CRP was 12.19 ± 9.32, both of which significantly decreased by 6 months. This trend mirrors findings by Patel et al. (2022), where ESR and CRP levels were markedly reduced following targeted disease-modifying therapy, reinforcing their role as key biomarkers for treatment efficacy monitoring. Clinical indices such as the Clinical disease activity index (CDAI), SDAI, and DAS28 showed significant improvements over the study period. Similar reductions were observed in studies like that of Thompson et al. (2017), which reported a mean decrease in DAS28 from 5.3 to 2.1 after 6 months of biologic therapy. These findings highlight the effectiveness of intervention strategies in reducing disease activity and improving patient outcomes. Pain assessment using the visual analog scale (VAS) also showed a marked reduction, from 5.14 ± 1.85 at baseline to 0.60 ± 0.57 at 6 months. These results align with the work of Anderson et al. (2016), who found that targeted therapy led to a 75% reduction in VAS scores within a similar timeframe. Overall, the findings of this study are consistent with existing literature, further validating the observed trends in disease activity, inflammatory markers, and pain relief. The significant P-values associated with these outcomes reinforce the reliability of our findings, highlighting the effectiveness of the treatment approaches utilized. The addition of Glucocorticoids and Diclofenac in the initial phase of treatment was necessary for symptomatic relief and reduction of inflammatory markers. However, it is important to acknowledge that their use introduces a potential confounding effect in the short term. The anti-inflammatory effects of steroids and NSAIDs may temporarily lower clinical scores and inflammatory markers, thereby influencing early assessments of disease activity. Despite this initial impact, the final results of the study were assessed at the 6-month follow-up was primarily reflect the efficacy of DMARD therapy. Since glucocorticoid was only administered for a short duration (3 weeks), their influence was not persisting throughout the study period. By the time of the final assessment, disease control was attributed to the long-term action of MTX, HCQ, and SAAZ, thereby ensuring that the study outcomes are a true reflection of DMARD efficacy rather than short-term symptomatic interventions.

Statistical analysis

Data were entered into Excel and analyzed using Statistical Package for the Social Sciences and Graph Pad Prism. Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests were used to compare independent groups, while paired t-tests accounted for correlations in paired data. Chi-square tests (including Fisher’s exact test for small sample sizes) were used for categorical data comparisons. P ≤ 0.05 were considered statistically significant. The age distribution of participants in our study demonstrated a statistically significant variation (P < 0.00001). The majority of participants belonged to the 41–50 age group (60.0%, n = 30), followed by the 51–60 age group (18.0%, n = 9), the 21–30 age group (14.0%, n = 7), and the 31–40 age group (8.0%, n = 4). The highly significant P-value suggests that the observed distribution is unlikely to be due to random variation, highlighting the predominance of middle-aged individuals in the study population. The mean age of the sample population is 42.7 ± 8.82 years, indicating that most individuals’ ages fall within this range around the mean. The sex distribution in the study population was highly significant (P < 0.00001), with a predominant representation of females (88.0%, n = 44) compared to males (12.0%, n = 6). This significant difference suggests a strong female predominance in the study cohort, which may reflect the known higher prevalence of the condition under investigation among females. The distribution of comorbidities among study participants was statistically significant (P < 0.00001). DM was the most prevalent comorbidity, observed in 12.0% (n = 6) of participants, followed by HTN in 6.0% (n = 3) and a combination of DM and HTN in 2.0% (n = 1). The highly significant P-value indicates that the occurrence of comorbid conditions was not random, suggesting a potential association with the study variables. The distribution of RF positivity among participants was highly significant (P < 0.00001). A majority of the study population tested positive for RA (88.0%, n = 44), while only a small proportion was RA-negative (12.0%, n = 6). The highly significant P-value suggests that the observed distribution is unlikely due to chance, indicating a strong prevalence of RA positivity in the study cohort (Table 1).

The ESR showed a progressive decline over time (Fig. 1). At baseline (0 weeks), the ESR was 32.56 ± 17.37. By 4 weeks, it decreased to 28.04 ± 16.90, followed by a further reduction to 21.78 ± 11.68 at 12 weeks. At 6 months, the ESR reached 13.66 ± 5.79, indicating a consistent downward trend over the study period. (Table 2) The CRP levels showed a gradual decline over time. (Fig. 2) At baseline (0 weeks), the CRP level was 12.19 ± 9.32. By 4 weeks, it decreased to 8.56 ± 7.43, followed by a further reduction to 7.34 ± 5.90 at 12 weeks. At 6 months, the CRP level reached 4.18 ± 2.90, indicating a steady reduction in inflammation over the study period (Table 3). The CDAI showed a progressive decline over time (Fig. 3). At baseline (0 weeks), the CDAI was 13.32 ± 3.57. By 4 weeks, it reduced to 10.70 ± 3.18, followed by a further decrease to 7.64 ± 1.37 at 12 weeks. At 6 months, the CDAI reached 5.82 ± 1.37, indicating a significant improvement in disease activity over the study period (Table 4). The SDAI demonstrated a gradual reduction over time. At baseline (0 weeks), the SDAI was 22.28 ± 2.10. By 4 weeks, it decreased to 17.10 ± 4.43, followed by a further decline to 15.64 ± 2.15 at 12 weeks. At 6 months, the SDAI reached 13.22 ± 2.24, indicating a steady improvement in disease activity over the study period (Table 5). The DAS28 showed a significant reduction over time (Fig. 4). At baseline (0 weeks), the DAS28 was 5.20 ± 0.16. By 4 weeks, it decreased to 3.87 ± 0.51, followed by a further decline to 3.09 ± 0.45 at 12 weeks. At 6 months, the DAS28 reached 2.24 ± 0.25, indicating a consistent improvement in disease activity over the study period (Table 6). The VAS scores showed a marked reduction over time. At baseline (0 weeks), the VAS score was 5.14 ± 1.85. By 4 weeks, it decreased to 4.10 ± 1.36, followed by a further decline to 2.48 ± 0.95 at 12 weeks. At 6 months, the VAS score reached 0.60 ± 0.57, indicating significant pain relief and improvement over the study period (Table 7).

This study highlights the significant impact of disease-modifying anti-rheumatic drug (DMARD) therapy in reducing inflammation, disease activity, and pain in patients with RA. The observed decline in inflammatory biomarkers, including ESR and CRP, strongly correlated with improvements in disease activity indices such as the DAS28, CDAI, and SDAI. These findings emphasize the critical role of DMARD therapy in controlling systemic inflammation, preventing disease progression, and improving patient-reported outcomes, including pain relief as measured by the VAS. Importantly, the study reinforces the utility of inflammatory biomarkers in guiding treatment response, providing clinicians with objective measures to assess disease control. While the short-term impact of glucocorticoid therapy and NSAIDs may have contributed to initial symptom relief, the sustained reduction in biomarkers and disease activity over 6 months reflects the long-term efficacy of DMARDs, particularly MTX, HCQ, and SAAZ. Despite its strengths, the study has its limitations. Its retrospective design, relatively short follow-up period, absence of a control group, and limited biomarker assessment restrict its generalizability. The lack of radiographic evaluation also limits insights into structural disease progression and joint preservation. To build on these findings, future research should include randomized controlled trials with extended follow-up, larger sample sizes, detailed subgroup analysis (e.g., seropositive vs. seronegative RA), and imaging modalities to assess disease activity more comprehensively. Overall, the study supports the continued use of DMARDs as the cornerstone of RA management and underscores the need for personalized treatment strategies based on biomarker-driven monitoring. As RA treatment evolves, integrating novel biomarkers, genetic profiling, and advanced imaging techniques may further enhance individualized care, improving long-term patient outcomes and achieving sustained remission.

This study underscores the effectiveness of DMARDs in reducing both inflammatory biomarkers and disease activity in patients with RA. Significant reductions in ESR, CRP, and disease activity indices such as DAS28, CDAI, and SDAI were observed over a 6-month period, highlighting the therapeutic benefit of DMARD therapy. These improvements correlate with better clinical outcomes, including reduced pain levels as reflected by the VAS score. The findings emphasize the potential of DMARDs to control systemic inflammation and slow disease progression, ultimately enhancing the quality of life for RA patients. Clinicians should consider these markers when assessing treatment efficacy and guiding therapy decisions. Further long-term studies are needed to confirm these results and explore personalized treatment approaches.