Clinical Practice on Gout Management Among Filipino General Care Practitioners

INTRODUCTION

Gouty arthritis accounts for millions of outpatient visits annually and prevalence is still increasing especially involving younger age group. Based on the National Nutrition and Health Survey in 2003 reported an overall prevalence of gouty arthritis in the general population at 1.6 %. (1) Using data from national Hospital Ambulatory Medical Care survey and National Ambulatory Medical care survey from 2002, Krishnan et al found that in comparison to white ethnicity, Asian ethnicity was related with an increased likelihood of gout diagnosis (odds ratio [OR] 2.7, 95% confidence interval [95% CI] 1.1–7.7). (2)  Gout is the most prevalent inflammatory arthritis among Filipinos. (3,4)

The pathogenesis of urate crystal deposition is reasonably well understood, accompanied by appropriate urate-lowering therapy (ULT) and lifestyle advice, the objective of gout management is cure. (3)  Nonetheless, many patients continue to experience frequent and recurrent episodes of gout and progression of their disease. (5) This is because the condition is often misdiagnosed, or diagnosed late, and treatment is frequently suboptimal.  Many international and local guidelines have established evidence-based and consensus guidelines that covers on the different spectrum of the disease, its diagnosis and management.  However, despite provision of these guidelines and advancement in the understanding of gout, management of gout continues to be suboptimal.  This study aims to determine the current trends in gout management and adherence of general care practitioners to the 2008 Philippine Gout Guidelines.   

MATERIALS AND METHODS

Survey questionnaires were randomly distributed during annual conventions and various round table discussions involving members of Philippine College of Physicians (PCP) and the Philippine Academy of Family Physicians (PAFP) as participants. All members of both societies were eligible to participate in the study and a random sampling method was done to choose the respondents. All valid data from respondents were included in the analysis.

The survey questionnaire used was adapted from the previous study conducted among general care physicians in the Philippines in 2008. (1) The 1st Philippine Clinical Practice Guidelines in the Management of Gouty Arthritis included allopurinol only as the urate-lowering therapy available at that time. A minor modification in the questionnaire on the choice of urate lowering therapy includes febuxostat that was introduced in the market on 2010.

OUTCOMES

To determine the current trends in the management of gout and its concordance with the Philippine Clinical Practice Guidelines and the differences in the Gout management practice among physicians across duration of practice and between those who have and have not attended CME activities related to Gout.  To compare as well the current trend in gout management with an earlier survey done in 2008 based on the Philippine Clinical Practice Guidelines on Gout.

RESULTS

Demographics

There were 600 questionnaires distributed during conventions and round table discussions and a total of 390 (65%) responses were eligible for analysis.

Of the 390 respondents who participated in the survey, majority were females (237, 60.8%) with mean age of 37.32 + 10.22 (20-75) years. Almost half of the respondents were practicing in the provinces (49.2%) while 198 (50.8%) were within Metro Manila.  Duration of practice was classified in 4 categories as shown in Table 1. A little more than half of the respondents were in practice for at least 5 years. Similar proportion has not attended any CME activities related to gout.The survey questions covered diagnosis and treatment of gout. Treatment included management of acute gouty arthritis, prophylaxis against gout flares and management of chronic gout with comorbidities as well as monitoring for drug efficacy.

Statistical analysis

Tables 2-4 highlighted the distribution of responses to the main questions of this study with comparative responses to the 2008 survey using One-sample Chi Square Test and the binomial test.

Diagnosis of Gout

Less than three quarters (64.9%) of the respondents agreed to do synovial fluid examination in a patient suspected to be suffering from acute gouty arthritis which was similar to the study done by Hamijoyo et al (8). However, 29.3% in the former study vs 19% in our study would not need synovial fluid examination, while 15.9% in our study admitted not to have idea on the procedure vs 7.3% in the former study. Responses in this study were observed to be significantly different from the previous study (p<0.001).  Significant differences were also observed across length of practice (p=0.010). Physicians with 1 to 5 years of experience (71%) and those <1 year in practice (67.5%) agreed to do synovial fluid exam while 25% of physicians practicing for more than 10 years admitted not to have any idea on the procedure.  On the other hand, 77.5% who have attended CME activities think that synovial fluid should be examined in a patient who has not undergone crystal analysis in the past, while those who have not attended (22.7%) admitted not to have idea of such procedure. (p<0.001).

Majority (67.9%) would examine the synovial fluid specimen only once while 23.1% and 6.9% would have it done at least twice to 5x to as many times as possible respectively. These responses were similar to the responses in the former study (p= 0.737). Higher proportions of those who attended CME forum would examine synovial fluid more often vs those who did not attend. On the other hand, there were no differences in responses among physicians across duration of practice (p=0.742).

Management of Acute Gout

In an otherwise healthy patient, 236 (60.5%) of the respondents will give colchicine, 80 (20.5%) NSAIDS and 23 (6.02%) oral/intravenous (IV) corticosteroids during acute gouty arthritis while 6.7% will give allopurinol (6.7%), febuxostat (9.2%), and tramadol (3.1%).  There was a decrease in proportion of respondents who advise patients to take allopurinol (p<0.001); while more respondents chose oral corticosteroid (p<0.001) and colchicine (p<0.001) when compared to the former study. Febuxostat (p=0.001) and tramadol (0.009), but not colchicine (p=0.019), were the foremost choices among respondents who have been in practice for longer duration. No significant difference was observed between those who have and have not attended any CME activity.   

In patient with renal insufficiency defined as serum creatinine of 2.2mg/dl, majority of respondents (35.1%) chose colchicine, 4.6% NSAIDS, 19.5% oral/IV steroids, and 18.2% tramadol as the drug of choice.  When compared with former study, there was a significant reduction in allopurinol (p<0.001) and NSAID (p<0.001) prescription and increase in use of tramadol (p=0.001) and colchicine (p=0.023). No difference in prescription among respondents when duration of practice and attendance to CME fora were compared.

In general, colchicine was prescribed 3x daily in 30.3%, significantly higher compared to the former study (p<0.001), 15.9% gave it 2x daily and 5.4% once daily for 3 days. Other management schema included hourly dose of colchicine until pain relief in 10.5%, 16.7% would give colchicine hourly until abdominal toxicity sets in and until maximum of 6 tablets was reached in 17.4% There were no differences across length of practice and having attended CME forum or not (p<0.066)

Urate-lowering therapy

Most respondents 44.9% prescribed ULT after the 1st attack of gout, while 52.3% in the former study started ULT in asymptomatic hyperuricemia phase (p<0.001). Responses vary significantly across length of practice (p=0.001) wherein most respondents with <1year experience prescribed ULD after 1st attack. However, there was no difference among those with or without CME activity (p<0.004). 

Optimal time to start urate-lowering drugs (ULD)

Most responders (43.3%) prescribed ULD 1-2 weeks after gout flares, significantly higher than the former study (p<0.001) with 20% each after <1 week and >2 weeks of attack. Some (15.1%) still practiced giving ULD during acute gout flares Physicians who have been in practice for long start ULD during acute flare or less than a week from a flare vs newly practicing clinicians (p=0.020).  Majority of the respondents with and without CME attendance initiated ULD 1 to 2 weeks after gout flare.  However, significant differences were evident where more doctors without CME attendance  initiated urate-lowering agent 2 weeks after the acute gout attack while more doctors with CME attendance  gave it during the attack (p=0.004).

Prophylaxis for acute gout

Prophylaxis for acute gout was sometimes given in 35.1%, often in 13.6%, very often in 8.5%, rarely given in 19.5%, and never given in 22.3%.

For prophylaxis, 60% opted colchicine compared to 33.1% in the former study. NSAID was the choice among 43.2% in the former study (p<0.001). Among those who attended CME courses, colchicine was their choice while NSAID and steroid were the choices given by those who haven’t attended any CME activities (p=0.008).

One to 6 months duration of prophylaxis was the choice of 30.3%, while 17.8%respondents in the former study discontinued it as soon as serum uric acid normalized (p<0.001).

More than 80% respondents shared that their patients experienced gout attack when ULD was prescribed, rarely in 39.7%, sometimes in 22.3%, often in 16.9%, and very often in 5.6%, while 12.6% did not have any experience of gout flare in their patients.

Monitoring and treat-to-target

Prescription for ULD was given by >50% until SUA normalized then discontinued. Only a few (16.7%) continued ULD for a year, 10.3% prescribed it for 5 years while 13.3% gave it for life. (p<0.001)

More of those who have been in practice for long prescribe ULD until SUA normalized compared to younger practitioners who advise the drug for lifelong. (p=0.008)

The concept of treat-to-target has been introduced several years ago and it aimed to control gout flares and its complications. In patients without evident tophi, half of the respondents aimed for 6mg/dl of SUA while a more stringent level of 5mg/dl was recommended by 34.9% and 7mg/dl by 12.8% respondents. On the other hand, in patients with chronic tophaceous gout, a value of 5mg/dl was the aim of 46.9% respondents, 6mg/dl in 35.4% and 15.1% respondents aimed for 7mg/dl. No significant difference was observed between those with and without CME activities in the treat-to-target level.  

Overall, management of the various clinical phases of gout by general care practitioners has improved through time with some variation across different areas and duration of practice.

DISCUSSION

The Philippine Rheumatology Association (PRA) had published the 1st evidence-based gout management guidelines (7) with the goal of improving the standards of care for patients.  Interestingly, inappropriate management of gout is still a frequent occurrence among physicians. 

Over time several surveys and observational studies have been conducted involving general practitioners, internists, family physicians as well as rheumatologists evaluating their clinical practice in dealing with gout, its diagnosis and treatment and variable treatment strategies were reported. (8) In a local survey among Filipino physicians by Hamijoyo et al in 2008, showed various inconsistencies in the practice among physicians in the management of gout and efficient educational program to improve physician skills and in the diagnosis and clinical management of gout was recommended. (8)

The gold standard in the diagnosis of gout involves identification of MSU crystals under polarized light. (3-9) However, crystal identification has received little attention in clinical practice since its introduction. (9) Similarly, our study highlighted the inconsistent practice and knowledge of most clinicians in confirming gout diagnosis. Efforts in crystal identification should not be limited to just one or two attempts. (9)

Several studies showed that control of flares of gout is still far from adequate. Acute gout attacks are best managed using anti-inflammatory agents. In a systematic review pharmacologic treatments identified with evidence of efficacy for acute gout were colchicine, NSAIDS, corticosteroids (10,11) and animal derived corticotropin. (12)

Choice of treatment for acute attacks should take into consideration co-morbidities that will render absolute and relative contraindications most especially NSAIDs. NSAIDs are best avoided and colchicine dose should be adjusted according to renal function. Colchicine has been shown to have better pain relief compared to placebo while 6 randomized controlled trials compared NSAIDS and corticosteroid and found no statistical difference in pain and effectiveness outcomes and overall adverse effects between the two (12).  Among patients with elevated creatinine (2.2 mg/dl), colchicine was the drug of choice in 35%. There was a significant increase in the use of tramadol (p=0.001), and colchicine (p=0.023) in gout study compared to the former study. Also, 60% of the respondents gave colchicine as prophylaxis compared to NSAIDs (43.2%) in the former study (p<0.001), while 22.3% have never given any prophylaxis.

Our study has shown the practice of administering colchicine at hourly dose until GI toxicity sets in. Standard references (16,14) used the following regimen in giving colchicine during acute gouty arthritis: one tablet (0.5 mg or 0.6 mg) given every hour until relief of symptoms or gastrointestinal toxicity occurs, or a total of 4 to 10 tablets achieved. The dose should be adjusted based on renal function and should be avoided in patients with gastrointestinal side effect or toxicity. (15) However, in recent guidelines to avoid commonly associated abdominal and other related adverse effects, a dose of 0.5mg BID-QID is being recommended. (7, 10-11) 

Less than 20% initiate urate lowering drug during acute flare among physicians who have been in practice for long using febuxostat or allopurinol Evidences showed that any attempt to alter level of SUA (either initiating or withholding ULD) will further prolong the acute attack. Sudden fluctuations in the serum urate levels may tend to precipitate and may make an inflammatory reaction already in progress substantially worse by a major change in the serum urate concentration. (7) In a recent study of Xin Feng et al in 2015, showed that patients started on allopurinol during attack exhibited higher attack rates compared to those started later. (18) Nevertheless, in the recently published 2016 European League against Rheumatism (EULAR) Task Force for Gout, stated that some patients chose not to take prophylaxis but did not experience flare. (10) Two small trials have suggested that allopurinol initiation during an acute gout attack did not prolong the duration of flares nor worsen its severity as compared with delayed initiation. (17)

In a national survey involving US primary care physicians, a little less than 50% of the responders in clinical practice showed inappropriate dose of medications in the setting of renal disease and lack of prophylaxis in initiating ULT accounted for much of the lack of compliance with treatment recommendations. (8)

The best way to control recurrent flares of acute gout, management should focus on keeping sUA level low enough to deplete the body urate pool. To achieve this, the sUA must be reduced below the saturation point of MSU under physiological conditions. (18) This has been recognized in recent evidence-based recommendations from the EULAR Task Force for Gout, which recommend that the sUA should be reduced to a target of 6 mg/dl (360 mol/l). (10) Recommendations pointed out that the target sUA level should be linked to the saturation level of MSU rather than to the normal laboratory range which can vary between facilities and with time. The British Society of Rheumatology (BSR) has also published guidelines for the management of gout and these recommend a stricter sUA target of <5 mg/dl (<300 mol/l). (19) In patients without evident tophi, half  of the respondents ( 49.7%) would aim for 6mg/dl of serum uric acid level while a more stringent level of 5mg/dl in 34.9% and 7mg/dl in 12.8%.  On the other hand, in patients with chronic tophaceous gout, a sterner target value of 5mg/dl was aimed by 46.9%, 6mg/dl in 35.4% and a more lenient 15.1% aimed for 7mg/dl.

The optimal time to start ULT after an acute gout flare varied (20) Most respondents 44.9% prescribed urate-lowering therapy (ULT) after the 1st attack vs 52.3% of whom in the former study initiated ULT during symptom free period (p<0.001). The recent EULAR Guidelines for Gout recommended early initiation of ULT that is close to first attack. (10)

Early initiation of ULT decreased the time to attain the target, lowered the incidence of CKD (20), and certainly improved outcomes and cost was contained. (18) Whichever form of therapy used to achieve goal range of SUA resulted in near elimination of gout flares and improved tophus status over time. (5)

There is still a significant variability among clinicians in managing gout despite available clinical practice guidelines aimed to provide optimal health care to gout patients. (21) Inadequate management of hyperuricemia and gout leads to long term complications and increase morbidity. In the US national health survey, an improvement in gout management has been shown to be due to increase awareness on the part of the physician and patient. (2) Our study showed inconsistencies on the practice of physicians who have either attended continuing medical educational forums on gout or not.

CONCLUSION

Overall, this study showed that general care practitioners manage gout in accordance to the 2008 Philippine clinical practice guidelines. Gout management has significantly improved in some but not all aspects. However, focused educational fora might still serve as a very helpful approach to general care practitioners to engage in for optimal healthcare delivery in the community.