|Ahead of print publication
Measuring inflammatory arthritis in patients with systemic lupus erythematosus using clinical disease activity index
Shallu Verma, Shubha Bhalla, Anand Narayan Malaviya
Department of Rheumatology, ISIC Super Speciality Hospital, New Delhi, India
|Date of Submission||20-Dec-2019|
|Date of Acceptance||04-Jun-2020|
Anand Narayan Malaviya,
Flat 2015, Sector B-2, Vasant Kunj, New Delhi - 110 070
Source of Support: None, Conflict of Interest: None
Background: Inflammatory polyarthritis is seen in ~80% of patients with systemic lupus erythematosus (SLE); yet, there is no validated “instrument” for its assessment. The commonly used measures of disease activity, namely SLE Disease Activity Index 2000 (SLEDAI2K) and British Isles Lupus Assessment Group are complex and impractical for routine use in busy outpatient clinics. This “proof of concept” study's primary aim was to test clinical disease activity index (CDAI) as a possible instrument for measuring the joint disease in SLE that may have a face value and sensitivity to change. The secondary aim was to determine the efficacy of low-dose methotrexate in the SLE joint disease.
Materials and Methods: This open-label study included the Systemic Lupus International Collaborating Clinics criteria classifiable thirty patients with SLE with inflammatory polyarthritis as the main manifestation. SLE disease activity and the joint disease activity were assessed using SLEDAI2K and CDAI, respectively, at the baseline and in the follow-up. The CDAI and the SLEDAI2K scores were compared between the first and the last visit, as well as compared with each other, using a nonparametric test (Wilcoxon signed-rank test).
Results: CDAI scores improved significantly on treatment from a mean of 19.30 to 1.58 and in SLEDAI2K from 7.83 to 0.6, respectively; the pre- and the postintervention scores were statistically highly significant (P < 0.001) for both the CDAI and the SLEDAI2K. The degree of improvement as shown by SLEDAI2K change in scores and CDAI was statistically insignificant (P > 0.05), indicating similarity in their sensitivity to change. A significant number of patients achieved low disease activity status or remission in their joint disease.
Conclusion: CDAI appears to be sensitive to change with treatment. Therefore, it could be used as a tool for assessing inflammatory arthritis in SLE.
Keywords: Clinical disease activity index, inflammatory arthritis, joint disease assessment, systemic lupus erythematosus, systemic lupus erythematosus disease activity index
|How to cite this URL:|
Verma S, Bhalla S, Malaviya AN. Measuring inflammatory arthritis in patients with systemic lupus erythematosus using clinical disease activity index. Indian J Rheumatol [Epub ahead of print] [cited 2020 Sep 20]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=291588
| Introduction|| |
Inflammatory arthritis resembling rheumatoid arthritis (RA) is one of the common manifestations of systemic lupus erythematosus (SLE). In reports from India, the musculoskeletal involvement was the most common clinical manifestation, present in 71%–92% in different series with an average of 85%; the most frequent is a nonerosive inflammatory polyarthritis that resembled RA, seen in 80% of cases. Despite arthritis being the prominent manifestation in the majority of patients, there is no validated “instrument” for the assessment of inflammatory arthritis in SLE. In the absence of any SLE-dedicated validated tool for sequentially measuring arthritis activity, most rheumatologists rely on other composite SLE indices, namely the SLE Disease Activity Index 2000 (SLEDAI2K) or the British Isles Lupus Assessment Group index where the joints are only one of the large numbers of other disease domains. Therefore, these composite indices may not truly reflect the joint disease activity in SLE. Moreover, being rather complex to perform, they are impractical for a crowded outpatient clinic.
This “proof of concept” study was, therefore, planned to use 28 joint count for measuring arthritis in SLE as is now the recommended method for the assessment of the joints in RA. The primary aim of this study was to find whether a composite index that uses 28 joint count (e.g., clinical disease activity index [CDAI]), is sensitive to change if used in patients with SLE in whom arthritis is the predominant clinical manifestation. The secondary aim was to see if low-dose methotrexate (LD-MTX), the “anchor drug” for the treatment of RA, is also effective in arthritis of SLE. Considering the questionable role of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in assessing the SLE disease activity,, it was considered prudent to mainly use CDAI as the “instrument” of choice for, it does not require the values of ESR or CRP for the calculation. However, Disease Activity Score (DAS)-28, as well as the Simplified Disease Activity Index (SDAI) values, was also recorded at each visit automatically by the electronic medical record (EMR) (the EMR being used in this clinic, simultaneously records DAS28, CDAI, and SDAI, once data are entered). However, these indices were not used for any calculations.
| Materials and Methods|| |
Thirty patients with SLE, classifiable by the Systemic Lupus International Collaborating Clinics criteria and presenting predominantly with inflammatory polyarthritis, were included in this study. Those with major organ involvements (e.g., central nervous system, kidney, and others including major gastrointestinal, cardiovascular, pulmonary, and hematological involvement) were excluded from the study. The selected patients were treated on standard line that included general and lifestyle measures (Sun and ultraviolet light protection, balanced diet, aerobic exercises, counseling against smoking, Vitamin D and folic acid supplementation, and appropriate vaccinations) and hydroxychloroquine (HCQ). In addition, they were prescribed LD-MTX, the variable dose from 10 to 25 mg/week (subcutaneously at dose >15 mg/week), depending on clinical judgment. Glucocorticoid (GC) daily dose (maximum 16 mg methylprednisolone/day) was only prescribed at the start of the treatment and tapered off over 6–8 weeks. Some patients did require small doses of once-a-week GC (8–12 mg methylprednisolone) synchronized with LD-MTX. Disease activity in the joints was assessed at the baseline and at the last (3-month) follow-up. The clinical details were recorded in a specifically created rheumatology-specific EMR software “Medic-Aid” (Rheum Aid, AMLA MEDIQUIP28/1 Old Rajinder Nagar, New Delhi, India) that is being used in this clinic since 2007. The ethical clearance was obtained from the “Ethics Committee” for the use of patient data extracted anonymously and recorded on a password-protected “Excel” sheet. Only the authors had access to the results on the “Excel” sheet.
| Results|| |
There were 29 female (21 married) with only one male patient in the study. The mean age was 37.07 ± 12.9 years. The demographic features of these patients are given in [Table 1]. As can be seen, most of the patients were female. Major organs such as the nervous system (neuropsychiatric), kidney, cardiovascular system, gastrointestinal system, and serositis were not present in any one of them. All of them were typical, superficial mucocutaneous-arthritic SLE.
|Table 1: Demographic data of systemic lupus erythematosus patients (n=30) included in the study|
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The multimorbidities seen in the patients were as follows: two prominent acne on the face in two patients, Type 2 diabetes mellitus in one patient, essential hypertension in six patients, and hypothyroidism in four patients. The patients were taking treatment for hypertension, Type 2 diabetes mellitus, and hypothyroidism from their family/local physicians.
Changes in disease assessment scores–clinical disease activity index and systemic lupus erythematosus disease activity index 2000 on treatment
The patients showed statistically significant improvement on the prescribed treatment in their CDAI as well as in SLEDAI2K values during the follow-up. The mean CDAI at the baseline was 19.3 (standard deviation [SD] 13.97; standard error [SE] 2.55) that fell to a mean CDAI of 1.58 (SD 2.46; SE 0.449) (“P” < 0.0001). Thus, at the baseline ( first clinic visit), there were 21 of a total of thirty patients (70%) who were in “moderate” or “high” disease activity state as determined by the CDAI values. At the end of 3 months of treatment, all the thirty patients were in either in “remission” or in “low” disease state according to the CDAI values. This was statistically highly significant improvement in the mean values of CDAI from the baseline to the last values at the end of 3 months of follow-up treatment.
Similarly, there was statistically highly significant improvement in SLEDAI2K on the prescribed treatment; the mean SLEDAI2K value reduced from the baseline value of 7.83 (SD 3.99; SE 0.729) to 0.6 (SD 1.01; SE 0.186) (“P” <0.001) at the end of 3 months of follow-up treatment.
Comparison of clinical disease activity index and systemic lupus erythematosus disease activity index 2000 scores
The associations between CDAI, SLEDAI2K, and change in scores were analyzed pre- and postintervention separately. As can be seen, these two parameters correlated closely with no significant difference (P > 0.05) indicative of similar “sensitivity to change” in the disease activity of these two “instruments” [Table 2].
|Table 2: The fall in the values of Clinical Disease Activity Index as well as Systemic Lupus Erythematosus Disease Activity Index 2000 shows statistically no difference indicative of concordance (good correlation)|
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| Discussion|| |
The present study demonstrated that the CDAI, a composite index used in the assessment of RA, is also sensitive to change in SLE patients who were being treated with long-term low-dose MTX (synchronized with weekly GC dose), HCQ, and a short course of GC during the early period of treatment. Thus, one of the components of the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) “filter” namely “sensitivity to change with treatment” was fulfilled by CDAI., It was also demonstrated that the CDAI change (improvement) closely correlated with the change (improvement) in one of the standard validated SLE composite indices, namely the SLEDAI2K, providing the correctness or the “face value” to the use of CDAI according to the OMERACT “filters” for developing composite indices for the measurement of any disease activity. In addition, there was no significant difference in the improvement trend between these two instruments. Thus, the third component of the OMERACT “filter” namely “truth” also seems to have been fulfilled, strengthening the validity of CDAI for the use in SLE arthritis., Thus, the present “proof of concept” study shows that CDAI could be a possible composite index for the objectified routine assessment of the inflammatory synovitis in patients with SLE. The next step should be to prove their validity using the stepwise validation methodology as recommended by the OMERACT group, which can be planned and executed exactly as has been carried out for measuring the joint disease in patients with systemic sclerosis. This study also reconfirmed the efficacy of LD-MTX in treating SLE arthritis. There have been several earlier studies on the use of LD-MTX in SLE that have come to a similar conclusion. The present study also showed that, as measured by the CDAI score, significant improvement was demonstrated in the joint disease in patients with SLE treated with LD-MTX, HCQ, and weekly GC synchronized with MTX. It must be mentioned that GC is a very effective agent for the treatment of joint disease in SLE. Therefore, it could be argued that the improvement in joints was entirely due to the (up to) 1st 8 weeks of GC treatment. However, it is to be noted that the effect was still persisting till the last evaluation that was done at 12 weeks. Of course, the efficacy of weekly MTX synchronized with weekly GC can only be firmly established with a study with long-term follow-up.
The main disadvantage of the study was that it did not undertake a stepwise validation for the use of CDAI in SLE. Second, the study did not use the “categorical, dichotomous” American College of Rheumatology-European League against Rheumatism response criteria to determine the efficacy of LD-MTX. The use of instruments for “continuous measure” (e.g., CDAI), is not ideal for measuring the drug response. Therefore, CDAI may not be an ideal tool to be used in drug trials. Similarly, ultrasonic joint examination for assessing synovitis was not used that could have given an inaccurate measure of joint inflammation.
| Conclusion|| |
The present study demonstrated promise for the use of CDAI as the composite index for routine assessment of the joint disease activity in SLE sequentially in a crowded outpatient clinic. However, appropriate validation would be necessary before it could be recommended for routine use. In a recent “Editorial” entitled “Assessing joint inflammation-a way forward for SLE trials,” van Vollenhoven has extensively discussed the problems of assessing SLE disease activity in drug trials. He has argued that accurate assessment of joint inflammation in patients with SLE (using ultrasound method) may be a robust primary endpoint for drug trials in SLE. Our study could be a small step toward this goal.
Authors shall like to thank Drs. Sanjiv Kapoor and Shriram Garg, consultant rheumatologists at this hospital for their unstinting support for this work. The help of the specialist rheumatologist nurse in routine patient assessment and patient counseling is gratefully acknowledged.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]