ORIGINAL ARTICLE
Complementary and Alternative Medicine Use in Patients With Gout A Longitudinal Observational Study Estee Chan, MBChB,* Meaghan E. House, MPH,Þ Keith J. Petrie, PhD,þ Anne Horne, MBChB,Þ William J. Taylor, PhD, FRACP,§ and Nicola Dalbeth, MD, FRACP*Þ
Background: Complementary and alternative medicine (CAM) is frequently used by patients with arthritis. Objectives: The objectives of this study were to determine the frequency and type of CAM used for gout, to understand the clinical and psychological factors associated with CAM use in people with gout, and to determine whether patients using CAM have different clinical outcomes over 1 year. Methods: A total of 276 patients with gout for less than 10 years’ duration were recruited into a longitudinal observational study. Complementary and alternative medicine information including frequency, type, and cost of therapies were recorded at baseline. Gout disease activity (including flare frequency, tophus count, Health Assessment Questionnaire II, and serum urate) was assessed at baseline and after 1 year. Results: Complementary and alternative medicine use was reported by 23.9% of patients. A diverse range of CAM was used, most commonly dietary supplements and vitamins. Patients using CAM reported higher levels of concern about their gout but did not differ from those not taking CAM with respect to age, sex, years of formal education, ethnicity, illness perceptions, or gout disease activity measures at baseline or after 1 year. Total costs at baseline related to gout therapy were higher in the CAM users compared with those not using CAM (mean [SD] cost per month NZ $35.7 [NZ $69.0] vs NZ $7.1 [NZ $22.8]; P = 0.001). Conclusions: Complementary and alternative medicine use is not uncommon in patients with gout, albeit less than is reported in other rheumatic diseases. Inquiry about CAM use should be incorporated into the clinical assessment of patients with gout, to develop treatment plans that best suit the individual patient’s health beliefs. Key Words: gout, uric acid, vitamins, complementary therapies, alternative medicine (J Clin Rheumatol 2013;20: 16Y20)
G
out is a common inflammatory arthritis characterized by recurrent attacks of joint inflammation. Management of acute gout attacks requires treatment with nonsteroidal anti-inflammatory From the *Department of Rheumatology, Auckland District Health Board, and Departments of †Medicine and ‡Psychological Medicine, University of Auckland, Auckland; and §Department of Medicine, University of Otago Wellington, Wellington, New Zealand. This study was funded by Arthritis New Zealand, the University of Auckland, and the Henry Cotton Charitable Trust. The authors declare no conflict of interest. Correspondence: Estee Chan, MBChB, Department of Rheumatology, Auckland District Health Board, Private Bag 92024, Auckland Mail Centre, Auckland 1142, New Zealand. E-mail: [email protected]. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 1076-1608/14/2001Y0016 DOI: 10.1097/RHU.0000000000000059
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drugs, colchicine, or corticosteroids. Long-term urate-lowering therapy is used to normalize serum urate concentrations below saturation levels, typically with xanthine oxidase inhibitors and/ or uricosuric drugs. Arthritis is one of the most common indications for which patients seek complementary and alternative medicine (CAM) treatment. The World Health Organization defines CAM as ‘‘a broad set of health care practices that are not part of the country’s own tradition and are not integrated into the dominant healthcare system.’’1 Previous studies have identified 4 in 5 CAM consultations are related to rheumatologic conditions, and CAM use accounts for 30% of the treatment costs of rheumatic diseases.2,3 However, more than 80% of patients never reveal their use of CAM to their physicians.4 Despite the large body of research exploring CAM use in conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA), the type and frequency of CAM use have not been reported in patients with gout. The aims of this study were to determine the frequency and type of CAM use in patients with gout specifically for gout, to understand the clinical and psychological factors associated with CAM use, and to determine whether patients using CAM have different clinical outcomes over 1 year.
MATERIALS AND METHODS Patients with gout were recruited into a longitudinal observational study by community advertising and through primary and secondary care clinics from Auckland and Wellington, New Zealand. Inclusion criteria included a previous physician diagnosis of gout according to the American College of Rheumatology criteria,5 first episode of gout within the last 10 years, and the ability to complete forms in English and provide written informed consent. The New Zealand Multi Regional Ethics Committee approved this study. Detailed clinical and psychological assessments were undertaken at the baseline visit. Clinical data recorded include demographic details (age, sex, ethnicity), gout history (confirmation of diagnosis, disease duration, frequency of gout flares, gout treatments), comorbid conditions, medications, physical examination (including tophus count), and laboratory tests including serum urate level. Questionnaires included the Health Assessment Questionnaire (HAQ) II6; 100-mm pain visual analog scale; gout-specific Brief Illness Perception Questionnaire (BIPQ), which assesses 5 main illness perception dimensions, as well as items measuring the patient’s concern, understanding, and emotional response to the illness on a 0- to 10-point Likert scale7; and a gout-specific medication adherence scale related to urate-lowering therapy.7 Patients were also asked about their use of CAM for management of gout, as part of a self-care questionnaire. Participants were recruited into a comprehensive longitudinal observational study of gout management
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and outcomes and were not specifically recruited into a study of CAM use. The CAM questionnaire asked patients to list the types of treatment used, the frequency of use on a scale of 5 frequencies (never, rarely, sometimes, often, very often), and money spent on these therapies per month. Complementary and alternative medicine types included dietary supplements, vitamins, herbal medicines, acupuncture, heat treatment, massage therapy, spiritual healer, topical ointments, aromatherapy, naturopathy (a form of alternative medicine based on the belief of vitalism and which favors a holistic approach with noninvasive treatment and encourages minimal use of surgery and drugs8), homeopathy, and Ayurvedic medicine (a system of traditional medicine native to the Indian subcontinent). After 1 year, further information including frequency of gout flares and activity limitation using HAQ-II was obtained by mail survey. Repeat blood tests were also collected at 1 year for serum urate. Data were analyzed using SPSS (SPSS Inc, Chicago, IL) software. Means with SDs and percentages were used to describe the clinical characteristics of patients using CAM with those who were not. Differences between groups were analyzed using t tests and W2 tests. The measures of gout activity or response to therapy were prespecified as flare frequency, serum urate concentration, and activity limitation as assessed by HAQ-II. All tests were 2-tailed, and P G 0.05 was considered statistically significant.
RESULTS There were 276 patients in the study. Table 1 shows the clinical characteristics of all patients at baseline and at 1-year follow-up. The majority of patients were middle-aged men. Mean disease duration was 5.2 (3.7) years, and 165 (59.8%) were on allopurinol. Follow-up data were available in 236 patients (85.5%) after 1 year. Three patients died over the followup period, and the remaining 37 patients were lost to follow-up. There were no significant differences at baseline between all participants and those with follow-up data at year 1, including CAM use (data not shown). Any CAM use was reported in 66 (23.9%) of 276 patients. Nineteen patients (6.9%) reported taking CAM often or very
TABLE 1. Clinical Characteristics Baseline (n = 276) Age, y Male, n (%) Ethnicity, n (%) European Ma¯ori Pacific Asian Age at first episode, y Disease duration, y Allopurinol use, n (%) Tophus count Alcohol use, units/wk No. flares in preceding 3 mo Serum urate, mmol/L HAQ-II score
59 (14) 193 (70) 181 (66) 44 (18) 27 (9.8) 24 (8.7) 54 (14.9) 5.2 (3.7) 165 (59.8) 0.56 (1.9) 3.3 (5.8) 2.43 (9.4) 0.40 (0.12) 0.49 (0.59)
Data are presented as mean (SD) unless specified.
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Year 1 (n = 236)
1.62 (5.5) 0.40 (0.11) 0.51 (0.62)
Complementary & Alternative Medicine in Gout
TABLE 2. CAM Use
Modality
No. (%) Users in the Entire Group (n = 276)
Dietary supplements Vitamins (all) Vitamin CYcontaining preparation Vitamin E Vitamin not otherwise specified Herbal medicines Acupuncture Heat treatment Massage therapy Spiritual healer Topical ointments Aromatherapy Naturopathy Homeopathy Ayurvedic medicine
38 (13.8) 16 (5.8) 13 (4.7) 1 (0.4) 2 (0.7) 15 (5.4) 5 (1.8) 4 (1.4) 3 (1.1) 3 (1.1) 2 (0.7) 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4)
often. A wide variety of CAM was reported by the patients (Table 2). The most common types of CAM were dietary supplements, followed by vitamins and herbal medicines (Table 2). Dietary supplements included fish oil, glucosamine, chondroitin, apple cider vinegar, and green lipped mussel extract. Not all patients listed the actual herbal medicine used, but those who did reported use of ‘‘Goji,’’ ‘‘garlic kem pepper,’’ ‘‘Chinese herbal remedies,’’ ‘‘herbal anti-inflammatories,’’ ‘‘Cirrulo herbal,’’ ‘‘herbal pill for gout,’’ and ‘‘Elmers herbal ointment.’’ Of the 66 patients reporting CAM use, 27 (41%) reported using more than 1 modality, and the mean (SD) number of CAM treatments used was 1.58 (0.82). Vitamin C use was reported in 13 (20%) of 66 patients using CAM. For those reporting CAM use, the mean cost of these treatments per month was NZ $29.10 (US $23.27) per patient. Acupuncture was the most expensive modality, with 1 patient reporting spending NZ $480 (US $383) per month on acupuncture alone. Complementary and alternative medicine use was reported in 14 (35%) of 40 Ma¯ori people, 3 (11%) of 27 Pacific people, 59 (32.6%) of 181 Europeans, and 11 (44%) of 25 Asians. There was no significant difference in the rates of overall CAM use between different ethnicities. However, there were some differences in the types of CAM used, with higher use of herbal therapies and acupuncture in those of Asian ethnicity (P = 0.03 and 0.01, respectively). Patients using CAM did not differ from those not using CAM with respect to age, sex, or years of formal education (all P 9 0.23). Similar rates of allopurinol were reported between the 2 groups (Table 3). There was no difference between these groups in the characteristics of gout activity at baseline, including flare frequency, tophus counts, serum urate, or activity limitation as measured by HAQ-II (Table 3). Similarly, after 1 year of follow-up, measures of gout activity or response to therapy including flare frequency, serum urate concentrations, and HAQ-II did not differ between these groups (Table 3). There was also no difference in the serum urate concentrations between patients taking vitamin C supplementation and all other patients (P = 0.82), or between patients taking vitamin C and those using other forms of CAM (P = 1.0). Health-related behaviors and illness perceptions were also explored in patients taking CAM. Adherence scores and www.jclinrheum.com
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TABLE 3. Clinical Characteristics of CAM Users and Non-CAM Users at Baseline and After 1 Year CAM Users
Non-CAM Users
Baseline (n = 276)
n = 66 (23.9%)
n = 210 (76.1%)
P
Allopurinol use, n (%) Alcohol use Tophus count No. of flares in preceding 3 mo Serum urate, mmol/L HAQ-II score Pain VAS (100 mm) BIPQ consequences score BIPQ timeline score BIPQ personal control score BIPQ treatment control score BIPQ identity score BIPQ concern score BIPQ understanding score BIPQ emotional responses score Medications adherence score Cost of prescribed treatment, NZ $ Cost of nonprescribed treatment, NZ $ Year 1 Follow-up (n = 236) No. flares in preceding 3 mo Serum urate, mmol/L HAQ-II score
38 (57.6) 3.9 (6.4) 0.77 (2.46) 4.11 (15.2) 0.39 (0.11) 0.47 (0.52) 18 (24) 4.25 (2.84) 7.35 (3.12) 5.74 (3.01) 7.64 (2.41) 5.05 (2.72) 7.17 (2.70) 7.05 (2.61) 3.95 (3.22) 40.7 (5.64) 5.60 (11.8) 29.5 (67.3) n = 54 (22.9%) 1.30 (2.41) 0.41 (0.11) 0.61 (0.63)
127 (60.5) 3.1 (5.7) 0.49 (1.67) 1.91(6.58) 0.41(0.13) 0.50 (0.62) 18 (25) 3.97 (3.30) 7.36 (3.37) 5.75 (3.16) 7.77 (2.81) 4.77 (3.14) 6.22 (3.30) 6.73 (2.74) 3.91 (3.55) 41.0 (5.68) 6.08 (19.6) 1.03 (6.61) n = 182 (77.1%) 1.72 (6.12) 0.39 (0.11) 0.47 (0.62)
0.67 0.42 0.40 0.27 0.44 0.73 0.88 0.51 0.99 0.98 0.73 0.49 0.02 0.40 0.93 0.75 0.81 0.001 0.53 0.45 0.24
Data are presented as mean (SD) unless specified. VAS indicates visual analog scale.
illness perceptions did not differ between those taking CAM and those not taking CAM (all P 9 0.50) with the exception of concern about gout; patients using CAM reported higher levels of concern about their gout on the BIPQ (mean gout BIPQ concern scores 7.2 [SD, 2.7] vs 6.2 [SD, 3.3]; P = 0.02) (Table 3). Total costs related to gout therapy were higher in the CAM users compared with those not using CAM (mean cost per month NZ $35.7 [SD, NZ $69.0] vs NZ $7.1 [SD, NZ $22.8]; P = 0.001). There was no difference in the costs of prescribed medicines for gout between the 2 groups (Table 3). However, the costs of nonprescribed therapies for gout were considerably higher in the CAM users (NZ $29.5 [NZ $67.3] vs NZ $1.03 [NZ $6.6]; P G 0.001).
DISCUSSION In this study, 23.9% of patients with gout reported using CAM. The use of CAM was relatively low in this study, compared with reported rates of between 28% and 90% in patients with RA and more than 80% in those with OA.9,10 The reason for the lower CAM use in people with gout is unclear but may be related to male health behavior and variations in socioeconomic status or health beliefs between different populations. Nevertheless, the observation that almost a quarter of patients with gout reported CAM use highlights the need to inquire about CAM in this patient group, to identify any potential interactions with conventional therapies and prevent adverse effects of certain CAM products. A diverse range of CAM was used by patients in this study. Dietary supplements and vitamins were most frequently used.
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A study of patients with RA has shown similar results, with nutritional supplements and touch therapies being the most widely used overall.11 A likely reason for the high percentage of use of dietary supplements is that they have been commercially popularized for the treatment of arthritis. In the case of RA, the efficacy of dietary supplementation in the form of omega-3 polyunsaturated fatty acid and fish oil as an adjunct for pain management and nonsteroidal anti-inflammatory drugYsparing agent has been demonstrated in several randomized controlled trials.12 Some, but not all, studies have also found glucosamine and chondroitin sulfate to be superior to placebo for pain reduction in knee OA.13 Of all the CAM type used by our patients, vitamin C supplementation is the only treatment that has been studied in published clinical trials of hyperuricemia and gout. Studies in the general population have shown that vitamin C supplementation results in significant reductions in serum urate concentrations.14 However, a recent randomized controlled trial in patients with gout receiving a modest dosage of vitamin C (500 mg/d) for 8 weeks has failed to demonstrate any clinically significant urate-lowering effects, despite the fact that plasma vitamin C levels increased.15 Only a minority of CAM users in our study of people with gout reported vitamin C use (20% of CAM users), and those taking vitamin C had similar serum urate concentrations to nonusers in this study, consistent with the recent clinical trial in gout. It should be noted that vitamin C has several important drug interactions that require special attention. Increased urinary excretion of ascorbic acid and decreased excretion of aspirin occur when these drugs are coadminstered.16 Several cases have also been reported in which ascorbic acid appeared to lower the effect of warfarin.16 Vitamin C is also known to increase absorption * 2013 Lippincott Williams & Wilkins
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of iron and is therefore contraindicated in patients with iron overload.16 Many studies have demonstrated that CAM accounts for significant personal health expenditures.3,11 In our study, total costs related to gout therapy were higher in the CAM users, because of increased costs of nonprescribed therapies. Mean costs of these treatments were NZ $29.10 (US $23.77) per month per patient, which were substantially higher than the average expenditure established by a previous study at US $100 per year.17 It has been reported that financial considerations are important for consumers choosing CAM options as expensive treatments are generally avoided and cost is a frequent reason to stop treatment.18 In our study, patients using CAM did not differ from those not using CAM with respect to age, sex, years of formal education, or ethnicity. However, there were some differences in the types of CAM used between ethnicities, with higher use of herbal therapies and acupuncture in those of Asian ethnicity. Previous studies have suggested that ethnicity and acculturation might influence use of CAM and that CAM users are more commonly middle-aged, female, of a higher academic background, with poorer self-rated health, and greater number of health complaints particularly chronic conditions.10,11 The reason behind this lack of difference in predictors of CAM use in our study is not clear. However, the finding that Asians use more herbal therapies and acupuncture would suggest that the selection of CAM may be influenced by geographical, cultural, and social factors. Furthermore, our study did not observe differences in gout disease activity outcomes between CAM users and those not using CAM at baseline or after 1 year. The reasons for this finding may be multiple, including a true lack of efficacy of CAM in general, or lack of efficacy of the types of CAM used, noting the wide range of therapies used by these patients. Previous studies have also identified CAM users as no more dissatisfied with or distrustful of conventional medication than non users, and indeed most users use CAM as adjunctive therapy alongside their traditional treatment.11 The similar rates of allopurinol use between CAM users and nonusers in this study suggest that patients with gout also use CAM as additional treatment rather than as a substitute for more conventional therapies. This study has a number of potential limitations due to the methodology followed and biases related to the patient cohort studied and patient recall bias. The study design did not allow us to examine whether CAM use was influenced by previous or current gout treatment or whether CAM use influenced patients’ acceptance of conventional therapy. The study did not make a distinction between whether CAM was used for treatment of flare, prevention of flare, or as a urate-lowering therapy. The amount and duration of CAM use were not recorded, and this may limit our ability to determine the potential impact of these therapies. The proportion of the cohort still using CAM at the conclusion of the first year of follow-up was not recorded, and this limits our ability to assess the duration of CAM use. Patients volunteered for this study, and this could lead to selection bias as patients who volunteered for such a study might have different medication beliefs and health-related behaviors compared with those who did not volunteer. Importantly, patients were not specifically recruited in a study of CAM use, and therefore, it is likely that our results do reflect the true frequency of CAM use in our population. In summary, this study has found that CAM use is not uncommon in patients with gout. However, the use of CAM was relatively low in this gout population compared with rates * 2013 Lippincott Williams & Wilkins
Complementary & Alternative Medicine in Gout
reported in other rheumatic diseases, such as RA and OA.9,10 A broad spectrum of CAM type was used by patients with gout, most commonly dietary supplements and vitamins. Aside from perceived concern about gout and costs of medications, we did not identify any major differences between CAM users and those not taking CAM with respect to demographic, clinical, or psychological characteristics. Furthermore, patients taking CAM did not have any difference in gout disease activity outcomes at baseline or after 1 year. These data suggest that questions about CAM use should be incorporated into the clinical assessment of patients with gout, to develop treatment plans that best suit the individual patient’s needs and health beliefs.
KEY POINTS 1. In this study of people with gout for less than 10 years, almost a quarter used CAM. 2. Dietary supplements and vitamins were the most common CAM type used. 3. Apart from perceived concern about gout, there were no major differences between CAM users and those not taking CAM with respect to demographic, clinical, and psychological characteristics. 4. Total costs related to gout therapy were higher in the CAM users, due to increased costs of nonprescribed therapies. 5. There was no difference in gout disease activity outcomes at baseline or after 1 year between CAM users and those not taking CAM.
REFERENCES 1. World Health Organization. Guidelines on Developing Consumer Information on Proper Use of Traditional, Complementary and Alternative Medicine. Geneva, Switzerland: WHO; 2004. 2. Thomas KJ, Carr J, Westlake L, et al. Use of non-orthodox and conventional health care in Britain. BMJ. 1991;302:207Y210. 3. Pullar T, Pullar T, Capell HA, et al. Alternative medicine: cost and subjective benefit in rheumatoid arthritis. BMJ. 1982;285:1629Y1631. 4. Zaman T, Agarwal S, Handa R. Complementary and alternative medicine use in rheumatoid arthritis: an audit of patients visiting a tertiary care centre. Natl Med J India. 2007;20:236Y239. 5. Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1997;20:895Y900. 6. Wolfe F, Michaud K, Pincus T. Development and validation of the health assessment questionnaire II: a revised version of the health assessment questionnaire. Arthritis Rheum. 2004;50:3296Y3305. 7. Dalbeth N, Petrie K, House M, et al. Illness perceptions in patients with gout and the relationship with progression of musculoskeletal disability. Arthritis Care Res. 2011;63:1605Y1612. 8. Sarris J, Wardle J. Clinical Naturopathy: An Evidence-Based Guide to Practice. Chatswood, New South Wales, Australia: Elsevier Australia; 2010. 9. Ernst E. Complementary and alternative medicine in rheumatology. Baillieres Best Pract Res Clin Rheumatol. 2000;14:731Y749. 10. Katz P, Lee F. Racial/ethnic differences in the use of complementary and alternative medicine in patients with arthritis. J Clin Rheumatol. 2007;13:3Y11. 11. Efithimiou P, Kukar M, Mackenzie CR. Complementary and alternative medicine in rheumatoid arthritis: no longer the last resort! HSS J. 2010;6:108Y111.
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12. Galarraga B, Ho M, Youssef HM, et al. Cod liver oil (n-3 fatty acids) as a non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology (Oxford). 2008;47:665Y669. 13. Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675. 14. Juraschek SP, Miller ER III, Gelber A. Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomised controlled trials. Arthritis Care Res. 2011;63:1295Y1306. 15. Stamp L, O’Donnell J, Frampton C, et al. Clinically insignificant effect of supplemental vitamin C on serum urate in patients
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with gout: a pilot randomized controlled trial. Arthritis Rheum. 2013;65:1636Y1642. 16. Apotex NZ Ltd. Apo-ascorbic acid datasheet. January 25, 2010. Available at: http://www.medsafe.govt.nz. Accessed June 23, 2013. 17. Boisset M, Fitzcharles MA. Alternative medicine use by rheumatology patients in a university health care setting. J Rheumatol. 1994;21:148Y152. 18. Rao JK, Kroenke K, Mihaliak KA, et al. Rheumatology patients’ use of complementary therapies: results from a one-year longitudinal study. Arthritis Rheum. 2003;49:619Y625.
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Complementary and Alternative Medicine Use in Patients With Gout A Longitudinal Observational Study Estee Chan, MBChB,* Meaghan E. House, MPH,Þ Keith J. Petrie, PhD,þ Anne Horne, MBChB,Þ William J. Taylor, PhD, FRACP,§ and Nicola Dalbeth, MD, FRACP*Þ
Background: Complementary and alternative medicine (CAM) is frequently used by patients with arthritis. Objectives: The objectives of this study were to determine the frequency and type of CAM used for gout, to understand the clinical and psychological factors associated with CAM use in people with gout, and to determine whether patients using CAM have different clinical outcomes over 1 year. Methods: A total of 276 patients with gout for less than 10 years’ duration were recruited into a longitudinal observational study. Complementary and alternative medicine information including frequency, type, and cost of therapies were recorded at baseline. Gout disease activity (including flare frequency, tophus count, Health Assessment Questionnaire II, and serum urate) was assessed at baseline and after 1 year. Results: Complementary and alternative medicine use was reported by 23.9% of patients. A diverse range of CAM was used, most commonly dietary supplements and vitamins. Patients using CAM reported higher levels of concern about their gout but did not differ from those not taking CAM with respect to age, sex, years of formal education, ethnicity, illness perceptions, or gout disease activity measures at baseline or after 1 year. Total costs at baseline related to gout therapy were higher in the CAM users compared with those not using CAM (mean [SD] cost per month NZ $35.7 [NZ $69.0] vs NZ $7.1 [NZ $22.8]; P = 0.001). Conclusions: Complementary and alternative medicine use is not uncommon in patients with gout, albeit less than is reported in other rheumatic diseases. Inquiry about CAM use should be incorporated into the clinical assessment of patients with gout, to develop treatment plans that best suit the individual patient’s health beliefs. Key Words: gout, uric acid, vitamins, complementary therapies, alternative medicine (J Clin Rheumatol 2013;20: 16Y20)
G
out is a common inflammatory arthritis characterized by recurrent attacks of joint inflammation. Management of acute gout attacks requires treatment with nonsteroidal anti-inflammatory From the *Department of Rheumatology, Auckland District Health Board, and Departments of †Medicine and ‡Psychological Medicine, University of Auckland, Auckland; and §Department of Medicine, University of Otago Wellington, Wellington, New Zealand. This study was funded by Arthritis New Zealand, the University of Auckland, and the Henry Cotton Charitable Trust. The authors declare no conflict of interest. Correspondence: Estee Chan, MBChB, Department of Rheumatology, Auckland District Health Board, Private Bag 92024, Auckland Mail Centre, Auckland 1142, New Zealand. E-mail: [email protected]. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 1076-1608/14/2001Y0016 DOI: 10.1097/RHU.0000000000000059
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drugs, colchicine, or corticosteroids. Long-term urate-lowering therapy is used to normalize serum urate concentrations below saturation levels, typically with xanthine oxidase inhibitors and/ or uricosuric drugs. Arthritis is one of the most common indications for which patients seek complementary and alternative medicine (CAM) treatment. The World Health Organization defines CAM as ‘‘a broad set of health care practices that are not part of the country’s own tradition and are not integrated into the dominant healthcare system.’’1 Previous studies have identified 4 in 5 CAM consultations are related to rheumatologic conditions, and CAM use accounts for 30% of the treatment costs of rheumatic diseases.2,3 However, more than 80% of patients never reveal their use of CAM to their physicians.4 Despite the large body of research exploring CAM use in conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA), the type and frequency of CAM use have not been reported in patients with gout. The aims of this study were to determine the frequency and type of CAM use in patients with gout specifically for gout, to understand the clinical and psychological factors associated with CAM use, and to determine whether patients using CAM have different clinical outcomes over 1 year.
MATERIALS AND METHODS Patients with gout were recruited into a longitudinal observational study by community advertising and through primary and secondary care clinics from Auckland and Wellington, New Zealand. Inclusion criteria included a previous physician diagnosis of gout according to the American College of Rheumatology criteria,5 first episode of gout within the last 10 years, and the ability to complete forms in English and provide written informed consent. The New Zealand Multi Regional Ethics Committee approved this study. Detailed clinical and psychological assessments were undertaken at the baseline visit. Clinical data recorded include demographic details (age, sex, ethnicity), gout history (confirmation of diagnosis, disease duration, frequency of gout flares, gout treatments), comorbid conditions, medications, physical examination (including tophus count), and laboratory tests including serum urate level. Questionnaires included the Health Assessment Questionnaire (HAQ) II6; 100-mm pain visual analog scale; gout-specific Brief Illness Perception Questionnaire (BIPQ), which assesses 5 main illness perception dimensions, as well as items measuring the patient’s concern, understanding, and emotional response to the illness on a 0- to 10-point Likert scale7; and a gout-specific medication adherence scale related to urate-lowering therapy.7 Patients were also asked about their use of CAM for management of gout, as part of a self-care questionnaire. Participants were recruited into a comprehensive longitudinal observational study of gout management
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and outcomes and were not specifically recruited into a study of CAM use. The CAM questionnaire asked patients to list the types of treatment used, the frequency of use on a scale of 5 frequencies (never, rarely, sometimes, often, very often), and money spent on these therapies per month. Complementary and alternative medicine types included dietary supplements, vitamins, herbal medicines, acupuncture, heat treatment, massage therapy, spiritual healer, topical ointments, aromatherapy, naturopathy (a form of alternative medicine based on the belief of vitalism and which favors a holistic approach with noninvasive treatment and encourages minimal use of surgery and drugs8), homeopathy, and Ayurvedic medicine (a system of traditional medicine native to the Indian subcontinent). After 1 year, further information including frequency of gout flares and activity limitation using HAQ-II was obtained by mail survey. Repeat blood tests were also collected at 1 year for serum urate. Data were analyzed using SPSS (SPSS Inc, Chicago, IL) software. Means with SDs and percentages were used to describe the clinical characteristics of patients using CAM with those who were not. Differences between groups were analyzed using t tests and W2 tests. The measures of gout activity or response to therapy were prespecified as flare frequency, serum urate concentration, and activity limitation as assessed by HAQ-II. All tests were 2-tailed, and P G 0.05 was considered statistically significant.
RESULTS There were 276 patients in the study. Table 1 shows the clinical characteristics of all patients at baseline and at 1-year follow-up. The majority of patients were middle-aged men. Mean disease duration was 5.2 (3.7) years, and 165 (59.8%) were on allopurinol. Follow-up data were available in 236 patients (85.5%) after 1 year. Three patients died over the followup period, and the remaining 37 patients were lost to follow-up. There were no significant differences at baseline between all participants and those with follow-up data at year 1, including CAM use (data not shown). Any CAM use was reported in 66 (23.9%) of 276 patients. Nineteen patients (6.9%) reported taking CAM often or very
TABLE 1. Clinical Characteristics Baseline (n = 276) Age, y Male, n (%) Ethnicity, n (%) European Ma¯ori Pacific Asian Age at first episode, y Disease duration, y Allopurinol use, n (%) Tophus count Alcohol use, units/wk No. flares in preceding 3 mo Serum urate, mmol/L HAQ-II score
59 (14) 193 (70) 181 (66) 44 (18) 27 (9.8) 24 (8.7) 54 (14.9) 5.2 (3.7) 165 (59.8) 0.56 (1.9) 3.3 (5.8) 2.43 (9.4) 0.40 (0.12) 0.49 (0.59)
Data are presented as mean (SD) unless specified.
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Year 1 (n = 236)
1.62 (5.5) 0.40 (0.11) 0.51 (0.62)
Complementary & Alternative Medicine in Gout
TABLE 2. CAM Use
Modality
No. (%) Users in the Entire Group (n = 276)
Dietary supplements Vitamins (all) Vitamin CYcontaining preparation Vitamin E Vitamin not otherwise specified Herbal medicines Acupuncture Heat treatment Massage therapy Spiritual healer Topical ointments Aromatherapy Naturopathy Homeopathy Ayurvedic medicine
38 (13.8) 16 (5.8) 13 (4.7) 1 (0.4) 2 (0.7) 15 (5.4) 5 (1.8) 4 (1.4) 3 (1.1) 3 (1.1) 2 (0.7) 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4)
often. A wide variety of CAM was reported by the patients (Table 2). The most common types of CAM were dietary supplements, followed by vitamins and herbal medicines (Table 2). Dietary supplements included fish oil, glucosamine, chondroitin, apple cider vinegar, and green lipped mussel extract. Not all patients listed the actual herbal medicine used, but those who did reported use of ‘‘Goji,’’ ‘‘garlic kem pepper,’’ ‘‘Chinese herbal remedies,’’ ‘‘herbal anti-inflammatories,’’ ‘‘Cirrulo herbal,’’ ‘‘herbal pill for gout,’’ and ‘‘Elmers herbal ointment.’’ Of the 66 patients reporting CAM use, 27 (41%) reported using more than 1 modality, and the mean (SD) number of CAM treatments used was 1.58 (0.82). Vitamin C use was reported in 13 (20%) of 66 patients using CAM. For those reporting CAM use, the mean cost of these treatments per month was NZ $29.10 (US $23.27) per patient. Acupuncture was the most expensive modality, with 1 patient reporting spending NZ $480 (US $383) per month on acupuncture alone. Complementary and alternative medicine use was reported in 14 (35%) of 40 Ma¯ori people, 3 (11%) of 27 Pacific people, 59 (32.6%) of 181 Europeans, and 11 (44%) of 25 Asians. There was no significant difference in the rates of overall CAM use between different ethnicities. However, there were some differences in the types of CAM used, with higher use of herbal therapies and acupuncture in those of Asian ethnicity (P = 0.03 and 0.01, respectively). Patients using CAM did not differ from those not using CAM with respect to age, sex, or years of formal education (all P 9 0.23). Similar rates of allopurinol were reported between the 2 groups (Table 3). There was no difference between these groups in the characteristics of gout activity at baseline, including flare frequency, tophus counts, serum urate, or activity limitation as measured by HAQ-II (Table 3). Similarly, after 1 year of follow-up, measures of gout activity or response to therapy including flare frequency, serum urate concentrations, and HAQ-II did not differ between these groups (Table 3). There was also no difference in the serum urate concentrations between patients taking vitamin C supplementation and all other patients (P = 0.82), or between patients taking vitamin C and those using other forms of CAM (P = 1.0). Health-related behaviors and illness perceptions were also explored in patients taking CAM. Adherence scores and www.jclinrheum.com
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TABLE 3. Clinical Characteristics of CAM Users and Non-CAM Users at Baseline and After 1 Year CAM Users
Non-CAM Users
Baseline (n = 276)
n = 66 (23.9%)
n = 210 (76.1%)
P
Allopurinol use, n (%) Alcohol use Tophus count No. of flares in preceding 3 mo Serum urate, mmol/L HAQ-II score Pain VAS (100 mm) BIPQ consequences score BIPQ timeline score BIPQ personal control score BIPQ treatment control score BIPQ identity score BIPQ concern score BIPQ understanding score BIPQ emotional responses score Medications adherence score Cost of prescribed treatment, NZ $ Cost of nonprescribed treatment, NZ $ Year 1 Follow-up (n = 236) No. flares in preceding 3 mo Serum urate, mmol/L HAQ-II score
38 (57.6) 3.9 (6.4) 0.77 (2.46) 4.11 (15.2) 0.39 (0.11) 0.47 (0.52) 18 (24) 4.25 (2.84) 7.35 (3.12) 5.74 (3.01) 7.64 (2.41) 5.05 (2.72) 7.17 (2.70) 7.05 (2.61) 3.95 (3.22) 40.7 (5.64) 5.60 (11.8) 29.5 (67.3) n = 54 (22.9%) 1.30 (2.41) 0.41 (0.11) 0.61 (0.63)
127 (60.5) 3.1 (5.7) 0.49 (1.67) 1.91(6.58) 0.41(0.13) 0.50 (0.62) 18 (25) 3.97 (3.30) 7.36 (3.37) 5.75 (3.16) 7.77 (2.81) 4.77 (3.14) 6.22 (3.30) 6.73 (2.74) 3.91 (3.55) 41.0 (5.68) 6.08 (19.6) 1.03 (6.61) n = 182 (77.1%) 1.72 (6.12) 0.39 (0.11) 0.47 (0.62)
0.67 0.42 0.40 0.27 0.44 0.73 0.88 0.51 0.99 0.98 0.73 0.49 0.02 0.40 0.93 0.75 0.81 0.001 0.53 0.45 0.24
Data are presented as mean (SD) unless specified. VAS indicates visual analog scale.
illness perceptions did not differ between those taking CAM and those not taking CAM (all P 9 0.50) with the exception of concern about gout; patients using CAM reported higher levels of concern about their gout on the BIPQ (mean gout BIPQ concern scores 7.2 [SD, 2.7] vs 6.2 [SD, 3.3]; P = 0.02) (Table 3). Total costs related to gout therapy were higher in the CAM users compared with those not using CAM (mean cost per month NZ $35.7 [SD, NZ $69.0] vs NZ $7.1 [SD, NZ $22.8]; P = 0.001). There was no difference in the costs of prescribed medicines for gout between the 2 groups (Table 3). However, the costs of nonprescribed therapies for gout were considerably higher in the CAM users (NZ $29.5 [NZ $67.3] vs NZ $1.03 [NZ $6.6]; P G 0.001).
DISCUSSION In this study, 23.9% of patients with gout reported using CAM. The use of CAM was relatively low in this study, compared with reported rates of between 28% and 90% in patients with RA and more than 80% in those with OA.9,10 The reason for the lower CAM use in people with gout is unclear but may be related to male health behavior and variations in socioeconomic status or health beliefs between different populations. Nevertheless, the observation that almost a quarter of patients with gout reported CAM use highlights the need to inquire about CAM in this patient group, to identify any potential interactions with conventional therapies and prevent adverse effects of certain CAM products. A diverse range of CAM was used by patients in this study. Dietary supplements and vitamins were most frequently used.
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A study of patients with RA has shown similar results, with nutritional supplements and touch therapies being the most widely used overall.11 A likely reason for the high percentage of use of dietary supplements is that they have been commercially popularized for the treatment of arthritis. In the case of RA, the efficacy of dietary supplementation in the form of omega-3 polyunsaturated fatty acid and fish oil as an adjunct for pain management and nonsteroidal anti-inflammatory drugYsparing agent has been demonstrated in several randomized controlled trials.12 Some, but not all, studies have also found glucosamine and chondroitin sulfate to be superior to placebo for pain reduction in knee OA.13 Of all the CAM type used by our patients, vitamin C supplementation is the only treatment that has been studied in published clinical trials of hyperuricemia and gout. Studies in the general population have shown that vitamin C supplementation results in significant reductions in serum urate concentrations.14 However, a recent randomized controlled trial in patients with gout receiving a modest dosage of vitamin C (500 mg/d) for 8 weeks has failed to demonstrate any clinically significant urate-lowering effects, despite the fact that plasma vitamin C levels increased.15 Only a minority of CAM users in our study of people with gout reported vitamin C use (20% of CAM users), and those taking vitamin C had similar serum urate concentrations to nonusers in this study, consistent with the recent clinical trial in gout. It should be noted that vitamin C has several important drug interactions that require special attention. Increased urinary excretion of ascorbic acid and decreased excretion of aspirin occur when these drugs are coadminstered.16 Several cases have also been reported in which ascorbic acid appeared to lower the effect of warfarin.16 Vitamin C is also known to increase absorption * 2013 Lippincott Williams & Wilkins
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of iron and is therefore contraindicated in patients with iron overload.16 Many studies have demonstrated that CAM accounts for significant personal health expenditures.3,11 In our study, total costs related to gout therapy were higher in the CAM users, because of increased costs of nonprescribed therapies. Mean costs of these treatments were NZ $29.10 (US $23.77) per month per patient, which were substantially higher than the average expenditure established by a previous study at US $100 per year.17 It has been reported that financial considerations are important for consumers choosing CAM options as expensive treatments are generally avoided and cost is a frequent reason to stop treatment.18 In our study, patients using CAM did not differ from those not using CAM with respect to age, sex, years of formal education, or ethnicity. However, there were some differences in the types of CAM used between ethnicities, with higher use of herbal therapies and acupuncture in those of Asian ethnicity. Previous studies have suggested that ethnicity and acculturation might influence use of CAM and that CAM users are more commonly middle-aged, female, of a higher academic background, with poorer self-rated health, and greater number of health complaints particularly chronic conditions.10,11 The reason behind this lack of difference in predictors of CAM use in our study is not clear. However, the finding that Asians use more herbal therapies and acupuncture would suggest that the selection of CAM may be influenced by geographical, cultural, and social factors. Furthermore, our study did not observe differences in gout disease activity outcomes between CAM users and those not using CAM at baseline or after 1 year. The reasons for this finding may be multiple, including a true lack of efficacy of CAM in general, or lack of efficacy of the types of CAM used, noting the wide range of therapies used by these patients. Previous studies have also identified CAM users as no more dissatisfied with or distrustful of conventional medication than non users, and indeed most users use CAM as adjunctive therapy alongside their traditional treatment.11 The similar rates of allopurinol use between CAM users and nonusers in this study suggest that patients with gout also use CAM as additional treatment rather than as a substitute for more conventional therapies. This study has a number of potential limitations due to the methodology followed and biases related to the patient cohort studied and patient recall bias. The study design did not allow us to examine whether CAM use was influenced by previous or current gout treatment or whether CAM use influenced patients’ acceptance of conventional therapy. The study did not make a distinction between whether CAM was used for treatment of flare, prevention of flare, or as a urate-lowering therapy. The amount and duration of CAM use were not recorded, and this may limit our ability to determine the potential impact of these therapies. The proportion of the cohort still using CAM at the conclusion of the first year of follow-up was not recorded, and this limits our ability to assess the duration of CAM use. Patients volunteered for this study, and this could lead to selection bias as patients who volunteered for such a study might have different medication beliefs and health-related behaviors compared with those who did not volunteer. Importantly, patients were not specifically recruited in a study of CAM use, and therefore, it is likely that our results do reflect the true frequency of CAM use in our population. In summary, this study has found that CAM use is not uncommon in patients with gout. However, the use of CAM was relatively low in this gout population compared with rates * 2013 Lippincott Williams & Wilkins
Complementary & Alternative Medicine in Gout
reported in other rheumatic diseases, such as RA and OA.9,10 A broad spectrum of CAM type was used by patients with gout, most commonly dietary supplements and vitamins. Aside from perceived concern about gout and costs of medications, we did not identify any major differences between CAM users and those not taking CAM with respect to demographic, clinical, or psychological characteristics. Furthermore, patients taking CAM did not have any difference in gout disease activity outcomes at baseline or after 1 year. These data suggest that questions about CAM use should be incorporated into the clinical assessment of patients with gout, to develop treatment plans that best suit the individual patient’s needs and health beliefs.
KEY POINTS 1. In this study of people with gout for less than 10 years, almost a quarter used CAM. 2. Dietary supplements and vitamins were the most common CAM type used. 3. Apart from perceived concern about gout, there were no major differences between CAM users and those not taking CAM with respect to demographic, clinical, and psychological characteristics. 4. Total costs related to gout therapy were higher in the CAM users, due to increased costs of nonprescribed therapies. 5. There was no difference in gout disease activity outcomes at baseline or after 1 year between CAM users and those not taking CAM.
REFERENCES 1. World Health Organization. Guidelines on Developing Consumer Information on Proper Use of Traditional, Complementary and Alternative Medicine. Geneva, Switzerland: WHO; 2004. 2. Thomas KJ, Carr J, Westlake L, et al. Use of non-orthodox and conventional health care in Britain. BMJ. 1991;302:207Y210. 3. Pullar T, Pullar T, Capell HA, et al. Alternative medicine: cost and subjective benefit in rheumatoid arthritis. BMJ. 1982;285:1629Y1631. 4. Zaman T, Agarwal S, Handa R. Complementary and alternative medicine use in rheumatoid arthritis: an audit of patients visiting a tertiary care centre. Natl Med J India. 2007;20:236Y239. 5. Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1997;20:895Y900. 6. Wolfe F, Michaud K, Pincus T. Development and validation of the health assessment questionnaire II: a revised version of the health assessment questionnaire. Arthritis Rheum. 2004;50:3296Y3305. 7. Dalbeth N, Petrie K, House M, et al. Illness perceptions in patients with gout and the relationship with progression of musculoskeletal disability. Arthritis Care Res. 2011;63:1605Y1612. 8. Sarris J, Wardle J. Clinical Naturopathy: An Evidence-Based Guide to Practice. Chatswood, New South Wales, Australia: Elsevier Australia; 2010. 9. Ernst E. Complementary and alternative medicine in rheumatology. Baillieres Best Pract Res Clin Rheumatol. 2000;14:731Y749. 10. Katz P, Lee F. Racial/ethnic differences in the use of complementary and alternative medicine in patients with arthritis. J Clin Rheumatol. 2007;13:3Y11. 11. Efithimiou P, Kukar M, Mackenzie CR. Complementary and alternative medicine in rheumatoid arthritis: no longer the last resort! HSS J. 2010;6:108Y111.
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12. Galarraga B, Ho M, Youssef HM, et al. Cod liver oil (n-3 fatty acids) as a non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology (Oxford). 2008;47:665Y669. 13. Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675. 14. Juraschek SP, Miller ER III, Gelber A. Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomised controlled trials. Arthritis Care Res. 2011;63:1295Y1306. 15. Stamp L, O’Donnell J, Frampton C, et al. Clinically insignificant effect of supplemental vitamin C on serum urate in patients
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with gout: a pilot randomized controlled trial. Arthritis Rheum. 2013;65:1636Y1642. 16. Apotex NZ Ltd. Apo-ascorbic acid datasheet. January 25, 2010. Available at: http://www.medsafe.govt.nz. Accessed June 23, 2013. 17. Boisset M, Fitzcharles MA. Alternative medicine use by rheumatology patients in a university health care setting. J Rheumatol. 1994;21:148Y152. 18. Rao JK, Kroenke K, Mihaliak KA, et al. Rheumatology patients’ use of complementary therapies: results from a one-year longitudinal study. Arthritis Rheum. 2003;49:619Y625.
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