|Year : 2018 | Volume
| Issue : 4 | Page : 255-258
Efficacy of short term non steroidal anti-inflammatory drugs in Indian patients with axial spondyloarthritis
Shubha Bhalla1, Shallu Verma1, Anand Narayan Malaviya2
1 Departments of Rheumatology, Indian Spinal Injuries Centre, New Delhi, India
2 Consultant Rheumatologist, ‘A&R Clinic’ and Visiting Sr Consultant Rheumatologist, Indian Spinal Injuries Centre, Superspeciality Hospital, New Delhi, India
|Date of Web Publication||18-Nov-2018|
Dr. Shubha Bhalla
Department of Rheumatology, Indian Spinal Injuries Centre, Vasant Kunj, New Delhi - 110 070
Source of Support: None, Conflict of Interest: None
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the first-line drugs for axial spondyloarthritis because of their high efficacy in controlling symptoms. However, the review of the literature shows that among Caucasian patients, only ~ 1/3rd with recent disease onset and only ~10% with the long-standing disease achieved partial or complete remission. The present study was, therefore, aimed at finding out how many Indian axSpA patients achieved low-disease activity state or remission over a short period of 12 weeks.
Methods: This was a retrospective study including 35 patients, both nonradiographic and radiographic axSpA, classified according to the Assessment of Spondyloarthritis International Society criteria (2009). Information was extracted from the electronic medical records for patients who had only received NSAIDs without any disease-modifying anti-rheumatic drugs or biologicals. The primary objective was to analyze the effect of continuous use of NSAIDs on their disease activity status as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) cutoff values at the baseline as compared to that after 3 months.
Results: A total of 31/35 patients continuously treated with NSAIDs for 12 weeks showed statistically significant improvement in their disease activity status as measured by ASDAS-CRP (P < 0.05). A total of 19/35 and 12/35 patients achieved remission (i.e., ASDAS-CRP < 1.3) and low disease state (i.e., ASDAS-CRP<2.1) after 12 weeks of treatment, respectively. A total of 4/35 patients were nonresponders; they were offered biologicals.
Conclusion: NSAIDs are effective in reducing ASDAS-CRP disease activity status. The efficacy of NSAIDs observed in this study was much higher than that reported in European/North American patients. The reason for this difference needs further study.
Keywords: Acute-phase reactants, axial spondyloarthritis, etoricoxib, nonsteroidal anti-inflammatory drugs, remission
|How to cite this article:|
Bhalla S, Verma S, Malaviya AN. Efficacy of short term non steroidal anti-inflammatory drugs in Indian patients with axial spondyloarthritis. Indian J Rheumatol 2018;13:255-8
|How to cite this URL:|
Bhalla S, Verma S, Malaviya AN. Efficacy of short term non steroidal anti-inflammatory drugs in Indian patients with axial spondyloarthritis. Indian J Rheumatol [serial online] 2018 [cited 2019 Dec 15];13:255-8. Available from: http://www.indianjrheumatol.com/text.asp?2018/13/4/255/238936
| Introduction|| |
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the cornerstone for the treatment of patients with axial spondyloarthritis (axSpA) for decades. Such patients require pain relief as well as suppression of inflammation and osteoproliferation to prevent structural damage, deformity, and disabilities. The three major effects of NSAIDs are the analgesic, anti-inflammatory, and antipyretic action; the first two properties are exploited for therapeutic purposes. However, its anti-inflammatory effect in axSpA has been controversial. Dougados et al. had demonstrated the efficacy of NSAIDs in reducing acute-phase reactants (APRs), a surrogate for inflammation. However, others have reported no effect on APRs, indirectly indicating that NSAIDs may not have any disease-modifying effect. Moreover, the reported response rate with NSAIDs in European patients has been rather low; only 35% in short duration disease and 12% in those with longer disease duration., The present work was therefore carried out to find out the response rate of patients with axSpA on treatment with NSAIDs in a routine rheumatology outpatient department.
| Methods|| |
The present work was an audit report (retrospective study) on consecutive patients being followed in the “Joint Disease Clinic”; data were collected from electronic medical record system from December 2009 to November 2017. During this period, 852 patients with SpA were seen. Among them, 455 had pure axial as classified with the 2009 Assessment of Spondyloarthritis International Society criteria, 12 had pure peripheral, and 385 had both axial and peripheral involvement. In the pure axial group, 35 patients who were NSAIDs naive or taking them “on demand” only were included in the study. The relevant information was extracted and recorded on a password-protected excel sheet and analyzed further.
The study excluded patients with peripheral involvement; psoriatic arthritis; inflammatory bowel disease-related SpA; reactive arthritis-related SpA; those with uveitis, dactylitis, or treated with disease-modifying anti-rheumatic drugs (DMARDs), or tumor necrosis factor inhibitors. The patients with associated comorbidities were also excluded from the study. They were prescribed only NSAIDs in full anti-inflammatory daily doses with proton pump inhibitor without glucocorticoids or DMARDs.
The disease assessment was carried out on the first visit and the follow-up visit at 3 months. The primary tool for assessing “improvement” in disease activity was Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) with validated ASDAS-CRP cutoff values, i.e., >3.5= “Very high disease activity (VHDA),” >2.1 but <3.5= “High disease activity (HDA),” <2.1–1.3= “Low disease activity (LDA),” ≤1.3= “inactive disease or remission.” The patients were also assessed with other clinical disease indices (secondary instruments) including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) with BASDAI >4 suggestive of VHDA, values from 3 to 4 indicating HDA, 1.1 to 2.9 indicating LDA, and BASDAI 0 to 1 indicating remission; Bath Ankylosing Spondylitis Functional Index (BASFI); Bath Ankylosing Spondylitis Metrology Index (BASMI); pain assessment on a numeric rating scale of 0–10 Visual Analog Scale (pain-VAS); and Bath Ankylosing Spondylitis Global assessment (BAS-G). Baseline erythrocyte sedimentation rate (ESR) and CRP values were compared with those at 3 months considering the normal cutoff values for ESR and CRP as 30 mm/h and 10 mg/L, respectively.
All the data were checked for normality using Shapiro–Wilk test. The prescores were compared with the postscores. Paired t-test or nonparametric equivalent (Wilcoxon signed rank test) was used for continuous variables (ESR, CRP, VAS [pain], BAS-G, BASFI, and BASMI), and McNemar's test was used for categorical variables (BASDAI, ASDAS-ESR, and ASDAS-CRP). The level of significance was P < 0.05 for all tests.
Institutional Ethics Committee's approval of our Centre for data extraction on a password-protected Excel® sheet was obtained before initiating the work.
| Results|| |
The study included a total of 35 patients. The male-to-female ratio was 10.6:1, and the mean age was 35.2 + 9.78 years, with median of 32 years ranging from 22 to 62 years. The median duration was 72 months. A total of 13/35 patients had a disease duration of <5 years; 24 patients were radiographic axSpA and 11 were nonradiographic-axSpA. Thirty-four patients were human leukocyte antigen-B27 positive (by polymerase chain reaction method). A total of 9/35 patients were smokers; 6 were light smokers and 3 were heavy smokers. A total of 29/35 patients were prescribed full dose of etoricoxib, 3 diclofenac, 2 naproxen daily, and 1 was prescribed indomethacin. Two patients on etoricoxib were switched to naproxen after a few weeks (due to intolerance). No significant adverse effects were reported among these patients. Disease status of the 35 axSpA patients on NSAIDs monotherapy at the baseline and follow-up of 12 weeks is summarized in [Table 1]. As can be seen, at baseline, out of 35 patients, 10 had VHDA, 16 had HDA, 6 LDA, and 3 were in remission. At the end of 3 months, 19 patients were in remission and 12 were in LDA state. Four of the 35 patients were nonresponders to NSAIDs, i.e., they did not achieve ASDAS-CRP of <2.1 suggestive of LDA at 12 weeks of follow-up. These patients were offered biologicals.
|Table 1: Disease activity status of 35 patients according to the cutoff values of Ankylosing Spondylitis Disease Activity Score-CRP at the baseline and after 12 weeks of continuous treatment with nonsteroidal anti-inflammatory drugs|
Click here to view
There was significant improvement in other parameters as well. Thus, in 35 patients, 19 and 22 had raised ESR and CRP, respectively. After 12 weeks, only 10 and 5 patients had high ESR and CRP, respectively (P < 0.05). Furthermore, there was significant improvement in secondary measures from the baseline to that after 12 weeks (P < 0.001 in each comparison), i.e., median BASDAI from 3.2 to 1.65, BASFI from 1.8 to 0.55, BASMI from 2.41 to 2, and BASG from 20 to 10.
In this study, 13 of the 35 axSpA patients had disease duration of <5 years; the other 22 patients had disease duration of >5 years. Among 13 patients with short duration disease, 6 attained ASDAS-CRP remission and 4 achieved LDA status. Among 22 patients with a long-term disease (i.e., >5 years), 13 and 8 attained ASDAS-CRP remission and LDA, respectively.
| Discussion|| |
The results of the present study showed that using ASDAS-CRP as the measure, a large proportion of axSpA patients achieved remission or LDA state with the use of continuous NSAIDs. This was in contrast to the European/North American patients with axSpA treated with the same group of drugs where the reported figures of partial remission in those with <5 years of disease were 35% and remission in 12% of patients with long-term disease.,
The reasons for the difference in response to NSAIDs in European/North American patients as compared to Indian patients were not obvious; literature search did not yield any similar study comparing patients from different geographic regions. The reasons could be genetic, or lifestyle factors, such as smoking, which is less prevalent in India (12%) than in Europe (28%) and America (17%) which adversely affect the treatment response. Food habits could also be playing some role. Indian spices including curcumin (abundantly used in Indian cooking) are known to be anti-inflammatory; this could have modified the response. Another possible reason could be related to the “class effect” of etoricoxib and its schedule. Most of the patients in this study were treated with etoricoxib, based on several reports showing its superiority over other NSAIDs in patients with SpA including those who may not have responded to TNF inhibitors. In a recent Bayesian network meta-analysis of clinical trials on the comparative efficacy of NSAIDs in AS, it was demonstrated that etoricoxib has a higher efficacy in axSpA as compared to other NSAIDs. Another reason for the possible higher efficacy of NSAIDs seen in the present study could be due to the schedule of “continuous” intake of the drug as against “on-demand” use. Several earlier studies have shown the superiority of “continuous” as against “on-demand” drug schedule. However, there are some contradictory reports as well.
The adverse effects of NSAIDs have always been a concern. However, some recent articles including a Cochrane review  have reported that overall serious adverse events related to nonselective NSAIDs and coxibs were similar and in the range of what would be expected in a group of SpA patients. Patients not exposed to NSAIDs had considerably more baseline comorbidities and increased risk for coronary artery disease.
There are some weaknesses in this study. The number of patients was small as was the duration of follow-up of 12 weeks only that would not lend it to analyze the radiographic changes. Furthermore, because of small sample size, the difference in response rate between patients on etoricoxib and other NSAIDs could not be analyzed.
However, this pilot study seems encouraging as NSAIDs led to patients achieving remission or LDA in significant numbers. With the prevalence of SpA in India reported between 0.1% and 0.2% and considering the low socioeconomic status of our country, NSAIDs would be cost-effective. However, this needs to be confirmed on a larger population for a longer period while balancing the side effects.
In summary, the present work demonstrates the efficacy of NSAIDs in reducing the disease activity status in patients with axSpA as shown by significant reduction of ASDAS-CRP at follow-up. The proportion of patients responding to NSAIDs in our population was much higher as compared to that reported among Caucasian patients. The reason for this could be a future research agenda.
The authors would like thank the department of rheumatology of their institute. Our special thanks to Dr. Vandana Phadke (statistician) for her help.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol 2016;12:282-95.
Benhamou M, Gossec L, Dougados M. Clinical relevance of C-reactive protein in ankylosing spondylitis and evaluation of the NSAIDs/Coxibs' treatment effect on C-reactive protein. Rheumatology (Oxford) 2010;49:536-41.
Escalas C, Trijau S, Dougados M. Evaluation of the treatment effect of NSAIDs/TNF blockers according to different domains in ankylosing spondylitis: Results of a meta-analysis. Rheumatology (Oxford) 2010;49:1317-25.
Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, et al.
Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: Results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis 2008;67:323-9.
Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, et al.
The development of assessment of Spondyloarthritis International Society Classification criteria for axial spondyloarthritis (Part II): Validation and final selection. Ann Rheum Dis 2009;68:777-83.
Machado PM, Landewé R, Heijde DV, Assessment of Spondyloarthritis International Society (ASAS). Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states. Ann Rheum Dis 2018.pii: annrheumdis-2018-213184.
Zochling J, Braun J. Remission in ankylosing spondylitis. Clin Exp Rheumatol 2006;24:S-88-92.
Wariaghli G, Allali F, Berrada K, Idrissi Z, Hmamouchi I, Abouqal R, et al.
Normative values for the bath ankylosing spondylitis functional index in the general population compared with ankylosing spondylitis patients in morocco. BMC Musculoskelet Disord 2012;13:40.
Poddubnyy D, Haibel H, Listing J, Märker-Hermann E, Zeidler H, Braun J, et al.
Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondyloarthritis. Arthritis Rheum 2012;64:1388-98.
van der Heijde D, Baraf HS, Ramos-Remus C, Calin A, Weaver AL, Schiff M, et al.
Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: Results of a fifty-two-week, randomized, controlled study. Arthritis Rheum 2005;52:1205-15.
Wang R, Dasgupta A, Ward MM. Comparative efficacy of non-steroidal anti-inflammatory drugs in ankylosing spondylitis: A Bayesian network meta-analysis of clinical trials. Ann Rheum Dis 2016;75:1152-60.
Kroon F, Landewé R, Dougados M, van der Heijde D. Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis. Ann Rheum Dis 2012;71:1623-9.
Sieper J, Listing J, Poddubnyy D, Song IH, Hermann KG, Callhoff J, et al.
Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: Results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis 2016;75:1438-43.
Kroon FP, van der Burg LR, Ramiro S, Landewé RB, Buchbinder R, Falzon L, et al.
Nonsteroidal antiinflammatory drugs for axial spondyloarthritis: A Cochrane review. J Rheumatol 2016;43:607-17.