|Ahead of print publication
Correlation of disease activity score using erythrocyte sedimentation rate and C-reactive protein with clinical disease activity index in rheumatoid arthritis patients
Viraj Panchal1, Puja Srivastava2, Dhaiwat Shukla2, Devang Rana3, Supriya Malhotra3, Sapan Pandya2
1 Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India
2 Department of Medicine, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India
3 Department of Pharmacology, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India
Department of Medicine, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat
Source of Support: None, Conflict of Interest: None
Background: Most patients coming to government hospital are from lower socioeconomic class and do not always get investigations done like ESR or CRP. A purely clinical index like CDAI would be a useful measure in such resource poor settings. Also there is scarce data on patterns of DMARD use from our country.
Objectives: To compare Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) and Disease Activity Score 28 using C-reactive protein (DAS28-CRP) with CDAI (Clinical Disease activity index) as measures of disease activity of RA and to analyze prescription patterns in RA patients.
Methods: Ours was a cross-sectional study of 4 months' duration. DAS28-ESR, DAS28-CRP and CDAI were calculated. The details of DMARDs used were recorded in proformas. Correlation was done using Spearman's Correlation Coefficient Test. To assess agreement between scores Cohen's kappa value was also evaluated. P value obtained <0.05 was considered significant.
Results: We evaluated a total of 104 patients most of them being females with a mean age of 45 years. The mean DAS28-ESR was 4.59 ± 1.36, mean DAS28-CRP was 3.86 ± 1.25 and mean CDAI was 16.9 ± 9.26 . The correlation coefficients of DAS28-ESR with DAS28-CRP was 0.894, DAS28-ESR with CDAI was 0.886 and DAS28-CRP with CDAI was 0.910. Methotrexate was the most prescribed drug as a mono therapy or in a combination with Hydroxychloroquine followed by Leflunomide, Sulfasalazine, and Prednisolone in that order.
Conclusion: The CDAI can substitute for SDAI or DAS 28 ESR/CRP and this would be very useful in a resource poor setting. Methotrexate was the most prescribed drug in our set up as mono or combination therapy.
Keywords: Clinical Disease Activity Index, disease activity, Disease Activity Score employing 28 joint count-C-reactive protein, Disease Activity Score employing 28 joint count-erythrocyte sedimentation rate, rheumatoid arthritis
|How to cite this URL:|
Panchal V, Srivastava P, Shukla D, Rana D, Malhotra S, Pandya S. Correlation of disease activity score using erythrocyte sedimentation rate and C-reactive protein with clinical disease activity index in rheumatoid arthritis patients. Indian J Rheumatol [Epub ahead of print] [cited 2019 Oct 22]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=266935
| Introduction|| |
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized with disabling inflammatory arthritis and some extra-articular involvement. Etiology of RA is unknown; however, role of inflammation and cytokines released with help of CD4+ T-cells and antibodies against self-antigens results in progressive joint destruction by the proliferation of synovial cells leading to synovitis and pannus formation, ultimately causing the destruction of the cartilage and ankylosis of the joint.
Disease activity in the patients can be calculated by different scales such as Disease Activity Score employing 28 joint count (DAS28) and Clinical Disease Activity Index (CDAI). However, DAS28 scale includes acute phase reactants in its calculations such as the use of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). ESR is being used broadly, although it can be affected by other factors such as age, gender, serum fibrinogen level, immunoglobulins, and rheumatoid factor. While CRP is a good indicator of inflammation than ESR and can show short-term changes, and usually, it is not affected by other conditions. Furthermore, calculating DAS28 score is time-consuming, as it requires laboratory tests done by the patient, and an online calculator or an app to calculate the scores., While a purely clinical tool like CDAI does not need any of the above-mentioned laboratory tests and can also prove useful.,
Moreover, most patients coming to government hospital are from lower socioeconomic class and do not always get investigations done. A purely clinical index like CDAI would be a useful measure in such resource-poor settings. Furthermore, there are scarce data on the patterns of use of disease modifying anti-rheumatic drugs (DMARDs) from our country.
The main objectives are as follows:
- To compare DAS28 using ESR and CRP with CDAI as measures of disease activity of RA
- To analyze prescription patterns in patients of RA.
| Methodology|| |
The NHL Institutional Review Board permission was taken on February 26, 2018. The study protocol including informed consent form, Morisky 8-item Medication Adherence questionnaire, and case record form documents were submitted to the board. Written informed consent was obtained from the patients. This was a cross-sectional study for duration of 4 months from March 2018 to June 2018 carried out on the patients visiting the Rheumatology Outpatient Department (OPD) at a City Municipal Hospital.
Patients with age >18 years, fulfilling the 2010 ACR and EULAR RA classification criteria, who had their blood ESR and CRP values were recruited. Patients having any other condition from which ESR and CRP levels could be affected (e. g., infections) were excluded from the study.
The patients' baseline data such as demographic details, presenting complaints, past, personal and family history, diagnosis, and detailed prescription were recorded in a case record form. Values of DAS28-ESR, DAS28-CRP, and CDAI were calculated and were labeled using defined cutoff points as remission, low, moderate, and high activity.,,
Data were entered into MS Excel 2016. Correlation of variable was done using Spearman's correlation coefficient test. To assess agreement between scores Cohen's kappa value was evaluated. P < 0.05 was considered statistically significant. Analysis was done using Statistical Package for the Social Sciences (SPSS) software version 23.0.
| Results|| |
A total of 104 patients were enrolled in the study. The sociodemographic and clinical characteristics of patients enrolled in the study are mentioned in [Table 1], it showed female predominance in this study with 89.42% with a mean age of 45.44 ± 13 years, and hypertension was the most common comorbidity.
|Table 1: Sociodemographic and clinical characteristics of rheumatoid arthritis patients (n=104)|
Click here to view
Disease activity in individual patients was calculated using three different scores, namely DAS28-ESR, DAS28-CRP, and CDAI. Most patients were in the moderate disease activity range. Spearman's correlation coefficient was evaluated for DAS28-ESR, DAS28-CRP, and CDAI. It was positive and ranged from 0.886 to 0.910, and correlation was extremely significant at all levels with P < 0.0001.
DAS28-ESR and DAS28-CRP correlated with r = 0.894, P < 0.0001. DAS28-CRP and CDAI correlated with r = 0.910, P < 0.0001. DAS28-ESR and CDAI correlated with r = 0.886, P < 0.0001. Correlation among the scores is shown in [Figure 1], [Figure 2], [Figure 3]. DAS28-CRP and CDAI had higher coefficient values than DAS28-ESR, and DAS-CRP which implies that DAS28-CRP correlated better with CDAI. To assess agreement between the measured scores, Cohen's kappa value was evaluated, which showed values of 0.378 with DAS28-ESR and DAS28-CRP, 0.517 with DAS28-CRP and CDAI, and 0.303 with DAS28-ESR and CDAI. Further, each score was cross-classified into different strata of disease activity using the predefined cutoff, shown in [Table 2], [Table 3], [Table 4]. It was seen from [Table 2] that when CDAI was compared with DAS28-ESR, a higher number of patients were in low and moderate activity using CDAI. At the same time, CDAI showed fewer patients in remission and high activity when compared to DAS28-ESR. Thus, overestimation of low disease activity (16 patients) and moderate activity (3 patients) was found in CDAI as compared to DAS28-ESR.
|Table 2: Cross comparison among number of patients in Disease Activity Score 28-erythrocyte sedimentation rate andClinical Disease Activity Index scores with disease activity in them (n=104)|
Click here to view
|Table 3: Cross comparison among number of patients in Disease Aactivity Score 28-C-reactive protein and Clinical Disease Activity Index scores with disease activity in them (n=104)|
Click here to view
|Table 4: Cross-comparison among number of patients in Disease Activity Score 28-erythrocyte sedimentation rate andDisease Activity Score 28-C-reactive protein scores with disease activity in them (n=104)|
Click here to view
|Figure 1: Scatter diagram showing the correlation between Disease Activity Score employing 28 joint count-C-reactive protein and Disease Activity Score employing 28 joint count-erythrocyte sedimentation rate. The disease activity values obtained with Disease Activity Score employing 28 joint count-C-reactive protein is positively correlated with disease activity values obtained with disease activity score employing 28 joint count-erythrocyte sedimentation rate. (r = 0.894,P < 0.0001, n = 104)|
Click here to view
|Figure 2: Scatter diagram showing the correlation between clinical Disease Activity Index and Disease Activity Score employing 28 joint count-C-reactive protein. The disease activity values obtained with the Clinical Disease Activity Index is positively correlated with disease activity values obtained with Disease Activity Score employing 28 joint count-C-reactive protein. (r = 0.910,P < 0.0001, n = 104)|
Click here to view
|Figure 3: Scatter diagram showing the correlation between clinical Disease Activity Index and Disease Activity Score employing 28 joint count-erythrocyte sedimentation rate. The disease activity values obtained with the Clinical Disease Activity index is positively correlated with disease activity values obtained with Disease Activity Score employing 28 joint count-erythrocyte sedimentation rate. (r = 0.886,P < 0.0001, n = 104)|
Click here to view
From [Table 3], CDAI showed higher number of patients in low activity (11 patients) and high activity (7 patients) when compared with DAS28-CRP. When DAS28-ESR was compared with DAS28-CRP in [Table 4], it was found that DAS28-CRP showed a considerable high number of patients in remission, low activity, and moderate activity compared to DAS28-ESR.
Methotrexate (MTX) was prescribed in 100 (96.15%) patients followed by hydroxychloroquine (HCQ) in 88 (84.61%) patients as monotherapy or in combination. Other drugs which were prescribed were leflunomide in 9 (8.65%) patients, prednisolone in 7 (6.73%) patients, and sulfasalazine in 3 (2.88%) patients. As monotherapy, MTX was prescribed in 15 (14.42%) patients and as combination in 87 (83.65%) patients. A total of 14 patients received three or more drugs in a combination as shown in [Table 5]. MTX was prescribed in a dose range of 7.5–25 mg once weekly, followed by HCQ given in varying dose range of 200–400 mg/day. Leflunomide was prescribed in the dose of 10–20 mg/day and prednisolone in the dose of 2.5–10 mg/day. Sulfasalazine was prescribed in a dose range of 1–3 g/day.
| Discussion|| |
Most RA patients are now treated as per the treat-to-target protocol, and for the same disease activity needs to be measured by validated scores. DAS28 ESR and DAS28 CRPs are easy to perform in day-to-day OPD, but one peculiar problem in countries such as India is that many patients do not get these done out of financial or other constraints, and hence, we need measures that can be clinically scored without the need for laboratory tests. CDAI is one such measure, and hence, we decided to test it and correlate it with the DAS28 ESR and CRP scores to see if they correlate. Our results confirm that they correlate well and that CDAI correlates better with DAS28 CRP than DAS28 ESR. Our results also showed that MTX and HCQ were the most commonly prescribed DMARDs.
As regard the correlation of disease activity measures, similar correlation was seen in a study done by Slama et al. on Moroccan population. Another study by Hamdi et al. showed similar results. A study was done in the eastern part of India by Ghosh et al. showed a strong correlation between DAS28-CRP and CDAI (correlation of 0.904 and 0.878 on two occasions, P < 0.001). Thus, for the selection of Disease Activity Index in a RA patient, any score can be used as per the characteristics and convenience of the patient, as all scores correlated well with each other with minor variations. It was also found that CDAI and DAS28-CRP often overestimated disease activity compared to DAS28-ESR, one of the reasons might be as per Fransen et al., that CRP changes sooner than ESR when there is a change in disease activity, as ESR is being influenced by different factors also. Hence, some use CRP as a better component of DAS28 scores. While Wolfe said that DAS28-ESR shows chronic conditions of the disease compared to DAS28-CRP.
Drugs prescribed in our study mostly included DMARDs as monotherapy or in combination. MTX was widely prescribed in our study as monotherapy as well as in combination with HCQ, leflunomide, sulfasalazine, or prednisolone. Most of the patients in our study were on a combination of MTX and HCQ. Fourteen patients received three or more drugs in a combination. MTX still remains the anchor drug in the treatment of RA and this showed in our prescription patterns too. HCQ remains the next commonly prescribed drug after MTX or in combination. Leflunomide can be an alternative to MTX alone or in combination. However, this combination is more hepatotoxic. Sulfasalazine is used as the second-line drug in RA. Prednisolone is often used as a bridge therapy with DMARDs. A study done by Aletaha and Smolen showed similar results: MTX was the preferred DMARD in patients with high disease activity, while HCQ and sulfasalazine were used in some patients with low disease activity. Another study done in Mumbai for drug utilization pattern and cost analysis in RA by Gawde et al., also showed that the most used combination was MTX and HCQ. Many other studies also have confirmed similar prescription patterns.,
In our study, no patients received biologics such as tumor necrosis factor-alpha inhibitors, rituximab, or small molecules such as tofacitinib. The reason for them not being prescribed could be their costs. Furthermore, most of our patients had moderate disease activity, which was well controlled with DMARDs. While in a study by Grijalva et al., the use of other biologics was also seen along with MTX as a DMARD.
A limitation of this study was the study population being small and limited ethnic groups enrolled. Other limitations included a single hospital data, which might not be applicable to other parts of the world. Follow-up data have not been assessed and thus the outcome not studied.
| Conclusion|| |
We conclude that CDAI can be scored in place of DAS28 ESR/CRP scores reliably to assess disease activity. MTX and HCQ remain the most frequently prescribed DMARDs as elsewhere in the world and India.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Choy E. Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 2012;51 Suppl 5:v3-11.
Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448-54.
Deodhar SD. C-reactive protein: The best laboratory indicator available for monitoring disease activity. Cleve Clin J Med 1989;56:126-30.
Aletaha D, Smolen J. The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI): A review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol 2005;23:S100-8.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd
, et al.
2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.
Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, et al.
Treating rheumatoid arthritis to target: Recommendations of an international task force. Ann Rheum Dis 2010;69:631-7.
Slama IB, Allali F, Lakhdar T, El Kabbaj S, Medrare L, Ngeuleu A, et al.
Reliability and validity of CDAI and SDAI indices in comparison to DAS-28 index in Moroccan patients with rheumatoid arthritis. BMC Musculoskelet Disord 2015;16:268.
Hamdi W, Néji O, Ghannouchi MM, Kaffel D, Kchir MM. Comparative study of indices of activity evaluation in rheumatoid arthritis. Ann Phys Rehabil Med 2011;54:421-8.
Ghosh A, Ghosh B, Pain S, Pande A, Saha S, Banerjee A, et al
. Comparison between DAS28, CDAI and HAQ-DI as tools to monitor early rheumatoid arthritis patients in Eastern India. Indian J Rheumatol 2011;6:116-22. [Full text]
Fransen J, Welsing PM, de Keijzer RM, Van Riel PL. Disease activity scores using C-reactive protein: CRP may replace ESR in the assessment of RA disease activity. Ann Rheum Dis 2004;62 Suppl 1:151.
Wolfe F. Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis. J Rheumatol 1997;24:1477-85.
Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gömör B, et al.
A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology (Oxford) 2000;39:655-65.
Aletaha D, Smolen JS. The rheumatoid arthritis patient in the clinic: Comparing more than 1,300 consecutive DMARD courses. Rheumatology (Oxford) 2002;41:1367-74.
Gawde SR, Shetty YC, Merchant S, Kulkarni UJ, Nadkar MY. Drug utilization pattern and cost analysis in rheumatoid arthritis patients – A cross-sectional study in tertiary care hospital, Mumbai. Br J Pharm Res 2013;3:37.
Agarwal V, Tiwari P. Treatment and monitoring costs in rheumatoid arthritis: Preliminary results from an Indian setting. Indian J Pharm Sci 2007;69:226. [Full text]
Pope JE, Hong P, Koehler BE. Prescribing trends in disease modifying antirheumatic drugs for rheumatoid arthritis: A survey of practicing Canadian rheumatologists. J Rheumatol 2002;29:255-60.
Grijalva CG, Chung CP, Stein CM, Mitchel EF Jr., Griffin MR. Changing patterns of medication use in patients with rheumatoid arthritis in a medicaid population. Rheumatology (Oxford) 2008;47:1061-4.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]