What are the most effective non-steroidal anti-inflammatory drugs for treating acute gout attacks. How do NSAIDs compare to placebo and other treatments in managing gout symptoms. What are the potential benefits and risks of using NSAIDs for gout.

Understanding Gout and Its Impact on Joint Health

Gout is a form of inflammatory arthritis characterized by the deposition of monosodium urate crystals in synovial fluid and other tissues. This painful condition typically progresses through three distinct phases:

1. Asymptomatic hyperuricemia
2. Episodes of acute gout
3. Chronic gouty arthritis

During acute gout attacks, patients experience severe pain, swelling, and inflammation in affected joints. These flares can significantly impact quality of life and mobility if left untreated. Effective management of acute gout is crucial for alleviating symptoms and preventing long-term joint damage.

The Role of NSAIDs in Acute Gout Treatment

Non-steroidal anti-inflammatory drugs (NSAIDs) are a cornerstone in the treatment of acute gout attacks. These medications work by reducing inflammation and pain associated with gout flares. NSAIDs encompass a broad class of drugs, including traditional NSAIDs and selective cyclo-oxygenase-2 (COX-2) inhibitors, also known as COXIBs.

Current treatment guidelines recommend using NSAIDs at maximum recommended doses for short durations to effectively manage acute gout attacks. But how do these medications compare to other treatment options, and what evidence supports their use?

Efficacy of NSAIDs vs. Placebo

A randomized controlled trial comparing the NSAID tenoxicam to placebo provided low-quality evidence on the effectiveness of NSAIDs in treating acute gout. The study, involving 30 participants, revealed that:

• 73.3% of participants taking tenoxicam experienced more than 50% reduction in pain after 24 hours, compared to only 26.7% in the placebo group.
• 33.3% of NSAID users showed more than 50% improvement in joint swelling after 24 hours, versus 13.3% in the placebo group.

These findings suggest that NSAIDs may offer significant short-term relief for acute gout symptoms. However, the small sample size and low-quality evidence warrant caution in interpreting these results.

Comparative Effectiveness of Different NSAIDs

While NSAIDs as a class show promise in managing acute gout, do certain NSAIDs outperform others? Moderate-quality evidence from four trials provides insights into the comparative effectiveness of various NSAIDs:

Tenoxicam vs. Other NSAIDs

Studies comparing tenoxicam to other NSAIDs found no significant differences in pain reduction, inflammation improvement, or adverse events. This suggests that tenoxicam may be as effective as other NSAIDs for treating acute gout.

Etoricoxib vs. Indomethacin

Two large trials compared etoricoxib (a COX-2 inhibitor) to indomethacin (a traditional NSAID). Key findings include:

• No significant difference in pain reduction between etoricoxib and indomethacin.
• Similar improvements in joint tenderness, swelling, and erythema for both medications.
• Comparable rates of adverse events, with a trend towards fewer gastrointestinal side effects with etoricoxib.

These results suggest that etoricoxib may be as effective as indomethacin for managing acute gout, with a potentially improved safety profile.

Safety Considerations for NSAID Use in Gout

While NSAIDs can effectively manage acute gout symptoms, their use is not without risks. Understanding the potential adverse effects is crucial for both healthcare providers and patients:

Common Side Effects

Reported adverse events in the reviewed studies included:

• Gastrointestinal disturbances (nausea, diarrhea, abdominal pain)
• Headache
• Dizziness
• Edema

It’s important to note that most studies reported similar rates of adverse events between different NSAIDs, suggesting a class-wide safety profile.

Serious Adverse Events

While rare, serious adverse events can occur with NSAID use. These may include:

• Gastrointestinal bleeding or ulceration
• Cardiovascular events
• Renal impairment

The risk of these serious events emphasizes the importance of using NSAIDs at the lowest effective dose for the shortest duration necessary to control symptoms.

NSAIDs vs. Other Gout Treatments

While NSAIDs are a common first-line treatment for acute gout, how do they compare to other available therapies? Several studies have explored this question:

NSAIDs vs. Colchicine

Limited evidence suggests that NSAIDs may be as effective as colchicine in managing acute gout symptoms. However, colchicine is associated with a higher incidence of gastrointestinal side effects, particularly at higher doses.

NSAIDs vs. Corticosteroids

Moderate-quality evidence indicates that NSAIDs and systemic corticosteroids have similar efficacy in treating acute gout. The choice between these treatments often depends on individual patient factors, such as comorbidities and potential drug interactions.

Optimizing NSAID Use in Acute Gout Management

To maximize the benefits of NSAIDs while minimizing potential risks, consider the following strategies:

1. Start treatment early: Initiating NSAID therapy at the first sign of a gout attack can lead to more rapid symptom resolution.
2. Use appropriate dosing: Follow guidelines for maximum recommended doses during acute attacks, but limit the duration of high-dose therapy.
3. Consider patient-specific factors: Take into account the patient’s age, comorbidities, and concomitant medications when selecting an NSAID.
4. Monitor for adverse effects: Regularly assess patients for potential side effects, especially those at higher risk for complications.
5. Combine with non-pharmacological measures: Encourage rest, ice application, and elevation of the affected joint to complement NSAID therapy.

Future Directions in Gout Research and Treatment

As our understanding of gout pathophysiology and treatment options continues to evolve, several areas warrant further investigation:

• Long-term safety and efficacy of NSAIDs in gout management
• Comparative effectiveness of NSAIDs vs. newer targeted therapies
• Personalized treatment approaches based on genetic and clinical factors
• Development of novel anti-inflammatory agents with improved safety profiles

Ongoing research in these areas may lead to more effective and tailored treatment strategies for individuals suffering from acute gout attacks.

In conclusion, NSAIDs remain a valuable tool in the management of acute gout, offering effective symptom relief for many patients. While they demonstrate comparable efficacy to other treatment options, the choice of therapy should be individualized based on patient characteristics and preferences. As research continues to advance our understanding of gout and its treatment, healthcare providers can leverage this knowledge to optimize care and improve outcomes for those affected by this painful condition.

Non-steroidal anti-inflammatory drugs for acute gout

Review

. 2014 Sep 16;(9):CD010120.

doi: 10.1002/14651858.CD010120.pub2.

Caroline M P G van Durme 
¹
, Mihir D Wechalekar, Rachelle Buchbinder, Naomi Schlesinger, Désirée van der Heijde, Robert B M Landewé

Affiliations

Affiliation

• ¹ Department of Rheumatology, Centre Hospitalier Universitaire de Liège, Avenue de l’Hopital 1, Liège, Belgium, 4000.

• PMID:

  25225849

• DOI:

  10.1002/14651858.CD010120.pub2

Review

Caroline M P G van Durme et al.

Cochrane Database Syst Rev.

2014.

. 2014 Sep 16;(9):CD010120.

doi: 10.1002/14651858.CD010120.pub2.

Authors

Caroline M P G van Durme 
¹
, Mihir D Wechalekar, Rachelle Buchbinder, Naomi Schlesinger, Désirée van der Heijde, Robert B M Landewé

Affiliation

• ¹ Department of Rheumatology, Centre Hospitalier Universitaire de Liège, Avenue de l’Hopital 1, Liège, Belgium, 4000.

• PMID:

  25225849

• DOI:

  10.1002/14651858.CD010120.pub2

Abstract

Background:

Gout is an inflammatory arthritis that is characterised by the deposition of monosodium urate crystals in synovial fluid and other tissues. The natural history of articular gout is generally characterised by three periods: asymptomatic hyperuricaemia, episodes of acute gout and chronic gouty arthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) including selective cyclo-oxygenase-2 (COX-2) inhibitors (COXIBs) are commonly used to treat acute gout. Published guidelines recommend their use to treat acute attacks, using maximum recommended doses for a short time.

Objectives:

To assess the benefit and safety of NSAIDs (including COXIBs) for acute gout.

Search methods:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for studies to 7 October 2013, the 2010 and 2011 ACR and EULAR abstracts and performed a handsearch of reference lists of articles. We searched the World Health Organization (WHO) trial register and ClinicalTrials.gov. We applied no date or language restrictions.

Selection criteria:

We considered all published randomised controlled trials (RCTs) and quasi-randomised controlled clinical trials that compared NSAIDs with placebo or another therapy (including non-pharmacological therapies) for acute gout. Major outcomes were pain (proportion with 50% or more reduction in pain or mean pain when the dichotomous outcome was unavailable), inflammation (e.g. measured by joint swelling/erythema/tenderness), function of target joint, participant’s global assessment of treatment success, health-related quality of life, withdrawals due to adverse events and total adverse events.

Data collection and analysis:

Two review authors independently selected the studies for inclusion, extracted the data, performed a risk of bias assessment and assessed the quality of the evidence using the GRADE approach.

Main results:

We included 23 trials (2200 participants).One trial (30 participants) of low-quality evidence compared an NSAID (tenoxicam) with placebo. It found that significantly more participants had more than 50% reduction in pain after 24 hours (11/15 participants) compared with those taking placebo (4/15 participants) (risk ratio (RR) 2.75, 95% confidence interval (CI) 1.13 to 6.72). A similar outcome was seen for more than 50% improvement in joint swelling after 24 hours (5/15 participants taking NSAIDs versus 2/15 participants taking placebo; RR 2.50, 95% CI 0.57 to 10.93). The trial did not measure function, participant global assessment of treatment success and health-related quality of life. There were no adverse events reported with the use of tenoxicam; two adverse events (nausea and polypuria) were reported in the placebo group. No between-group differences in outcome were observed after four days. Moderate-quality evidence based upon four trials (974 participants) indicated that NSAIDs and COXIBs produced similar benefits in terms of pain, swelling and global improvement, but COXIBs were associated with fewer adverse events. Pain reduction was 1.9 points on a 0- to 10-point scale with COXIBs (0 was no pain) while pain reduction with NSAIDs was 0.03 points lower or better (mean difference (MD) -0.03, 95% CI -0.19 to 0.13). Joint swelling in the COXIB group was 1.64 points on a 0- to 3-point scale (0 is no swelling) and 0.13 points higher with NSAIDs (MD 0.13, 95% CI -0.08 to 0.34). Function was not reported. Participant-reported global assessment was 1.56 points on a 0- to 4-point scale with COXIBs (0 was the best score) and was 0.04 points higher with NSAIDs (MD 0.04, 95% CI -0.12 to 0.20). Health-related quality of life assessed using the 36-item Short Form showed no evidence of a statistically significant between-group difference (MD 0.49, 95% CI -1.61 to 2.60 for the physical component). There were significantly fewer withdrawals due to adverse events in participants treated with COXIBs (3%) compared with NSAIDs (8%) (RR 2.39, 95% CI 1.34 to 4.28). There was a significantly lower number of total adverse events in participants treated with COXIBs (38%) compared with NSAIDs (60%) (RR 1.56, 95% CI 1.30 to 1.86).There was moderate-quality evidence based on two trials (210 participants) that oral glucocorticoids did not differ in pain reduction, function or adverse events when compared with NSAIDs. Pain reduction was 9.5 on a 0- to 100-point scale with glucocorticoids, pain reduction with NSAIDs was 1.74 higher or worse (MD 1.74, 95% CI -1.44 to 4.92). The trials did not assess inflammation. Function measured as walking disability was 17.4 points on a 0- to 100-point scale with glucocorticoids, function with NSAIDs was 0.1 lower or better (MD -0.10, 95% CI -4.72 to 4.52). The trials did not measure participant-reported global assessment and health-related quality of life. There were no withdrawals due to adverse events. There was no evidence of a difference in total number of adverse events with glucocorticoids (31%) versus NSAIDs (49%) (RR 1.58, 95% CI 0.76 to 3.28).

Authors’ conclusions:

Limited evidence supported the use of NSAIDs in the treatment of acute gout. One placebo-controlled trial provided evidence of benefit at 24 hours and little or no harm. We downgraded the evidence due to potential selection and reporting biases, and imprecision. While these data were insufficient to draw firm conclusions, they did not conflict with clinical guideline recommendations based upon evidence from observational studies, other inflammatory arthritis and expert consensus, which support the use of NSAIDs in acute gout.Moderate-quality evidence suggested that selective COX-2 inhibitors and non-selective NSAIDs are probably equally beneficial although COX-2 inhibitors are likely to be associated with significantly fewer total and gastrointestinal adverse events. We downgraded the evidence due to an unclear risk of selection and reporting biases. Moderate-quality evidence indicated that systemic glucocorticoids and NSAIDs were also equally beneficial in terms of pain relief. There were no withdrawals due to adverse events and total adverse events were similar between groups. We downgraded the evidence due to unclear risk of selection and reporting bias. There was low-quality evidence that there was no difference in function. We downgraded the quality due to unclear risk of selection bias and imprecision.

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MeSH terms

Substances

Treatment Options for Acute Gout

Fed Pract. 2016 Jan; 33(1): 35–40.

Author information Copyright and License information Disclaimer

Careful consideration of comorbidities and contraindications are important when determining the appropriate treatment of patients with gout.

Gout is an extremely painful arthritis initiated by innate immune responses to monosodium urate crystals that accumulate in affected joints and surrounding tissues. As a result, gout is characterized by painful arthritis flares followed by intervening periods of disease quiescence. Over time, gout can lead to chronic pain, disability, and tophi. Nearly 10% of those aged > 65 years report having gout. The overall prevalence in the U.S. population approaches 4%.1

Gout treatment has 2 overarching goals: alleviating the pain and inflammation caused by acute gout attacks and long-term management that is focused on lowering serum urate (sUA) levels to reduce the risk of future attacks. Alleviating the pain and inflammation of an acute attack is often complicated by patient characteristics, namely, other chronic health conditions that frequently accompany gout, such as diabetes mellitus (DM), chronic kidney disease (CKD), hypertension, and cardiovascular disease (CVD).

Patients with gout tend to be older and have multiple comorbidities that require the use of many medications.2 Because the VA patient population tends to be older, acute gout and attendant complications of treatment are an important consideration for VA health care providers (HCPs).

Recently, the American College of Rheumatology (ACR) released management recommendations for gout, including those for the treatment of acute gout. 3 The ACR recommends 3 first-line therapies, but limited guidance is provided for deciding among therapies. This article briefly reviews the relevant ACR recommendations and details important comorbidity and concomitant medication considerations in the treatment of acute gout.

Acute gout attacks are characterized by a rapid onset and escalation with joint pain typically peaking within 24 hours of attack onset. An acute attack often begins to remit after 5 to 12 days without intervention, but complete resolution may take longer in some patients.4 In one study, at 24 hours after attack onset, 16% of patients on placebo had > 50% reduction in pain compared with 70% that had no recovery at all.5 By 48 hours, one-third of patients on placebo achieved a 50% reduction in pain.6 Acute gout attacks are most commonly monoarticular, although 10% to 40% can involve ≥ 2 joints.7 The first metatarsophalangeal (MTP) joint is the initial site of involvement in about 50% of cases and is eventually observed in the majority of patients with gout (). 7 Other commonly affected joints include the midfoot, ankle, knee, wrist, elbow, and fingers. Most patients still reach peak pain within 24 hours with pain remitting predictably over 1 to 2 weeks. Chronic or variable intensity pain is more common among those with long-standing disease, polyarticular gout, or tophi.

Open in a separate window

Gout Involving the First Metatarsophalangeal Joint

The first metatarsophalangeal joint is the most common site for acute gout attacks, known as podagra.

Therapy for acute gout attacks aims to reduce pain and promote a full, early resolution. The ACR recommends pharmacologic therapy as first-line treatment with adjunctive topical ice and rest as needed.3 Typically, monotherapy is appropriate if the individual is experiencing mild-to-moderate pain affecting ≤ 2 joints of any size. Severe pain or attacks affecting multiple joints may benefit from initial combination therapy. Three first-line therapies are available: nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors, colchicine, or systemic glucocorticoids ().

Open in a separate window

Management of Acute Gout Attack^a

American College of Rheumatology (ACR) guidelines recommend 3 first-line treatments for acute gout attacks. Proper consideration of comorbidities helps optimize treatment.

^aIf inadequate response (< 50% pain decrease at 24 hours), switch agent or consider adding an additional agent; for severe gout attacks (eg, polyarticular), combination therapy may be considered. Adapted with permission from an unpublished figure created by Michael Pillinger, MD.

Few studies compare the efficacy of first-line therapeutic categories. There are no clinical trials directly comparing colchicine with NSAIDs or colchicine with glucocorticoids. No difference in mean reduction of pain and no differences in adverse events (AEs) were shown in a trial that compared glucocorticoids with NSAIDs.8 Thus, without further study, treatment choices made by HCPs are often guided by factors other than the existence of robust evidence.

Treatment with NSAIDs or COX-2 inhibitors should be initiated at the approved dose and continued until the gout attack has completely resolved. In one study, 73% of patients had pain reduction of ≥ 50% when taking NSAIDs relative to only 27% of patients on placebo.8 All available NSAIDs are considered effective, but only 3 NSAIDs are specifically approved for treatment of acute gout (naproxen, indomethacin, and sulindac). There is no evidence supporting one NSAID as being more effective than another; evidence fails to show a meaningful difference.8 Limited evidence indicates that selective COX-2 inhibitors, including celexocib, have similar efficacy as nonselective NSAIDs but may have fewer AEs, driven in part by fewer gastrointestinal (GI) events (6% vs 16% for GI events).8

Colchicine has long been used as prophylaxis for acute gout attacks and has been endorsed for the treatment of acute attacks. Recent evidence suggests that colchicine initially dosed at 1.2 mg followed by a single 0. 6-mg dose 1 hour later is as effective with fewer AEs compared with a traditional regimen of 1.2 mg followed by 0.6 mg every hour for up to 6 hours.5 About 40% of patients have 50% pain reduction within 24 hours and a 40% absolute risk reduction in AEs on this low-dose regimen. The efficacy of colchicine relative to other therapies is poorly defined, especially for patients presenting longer after attack onset. The ACR guidelines recommend colchicine only if treatment is initiated within 36 hours of attack onset, but this is based solely on expert consensus. Likewise, the above trial for low-dose colchicine did not provide information about dosing beyond the first 6 hours, leaving little guidance for follow-up treatment of residual pain beyond the 32 hours reported.5 Traditionally, one 0.6-mg dose is provided every 12 to 24 hours.3

Systemic glucocorticoids are also commonly used in treating acute gout.9 There was a small pain reduction benefit for prednisolone, but the difference was not clinically significant in one clinical trial comparing oral prednisolone 30 mg daily for 5 days vs a combination of indomethacin for 5 days and an initial intramuscular injection of diclofenac 75 mg. 10 The prednisolone group also had fewer patients with AEs, including abdominal pain (0% vs 30%) and GI bleeding (0% vs 11%). The lower incidence of short-term AEs may be a primary benefit of systemic glucocorticoids.11

Intra-articular glucocorticoids are not suggested first-line therapies but are commonly used by rheumatologists. 9 In an uncontrolled study conducted by Fernández and colleagues, intra-articular glucocorticoid injections helped to quickly resolve 20 out of 20 crystal-proven gout attacks.12 However, no randomized controlled trials have examined this approach. Although seemingly efficacious, other considerations are important for this modality. Intra-articular glucocorticoids may not be preferred for polyarticular attacks or attacks in difficult-to-aspirate joints. Additionally, intra-articular glucocorticoids have been anecdotally associated with rebound attacks (ie, attacks that occur shortly after resolution without other interventions). However, the Fernández study had no such attacks occur among participants. 12 Finally, septic arthritis must be ruled out as in any case of acute onset monoarticular arthritis.

Biologic agents targeting interleukin-1(IL-1) are not currently approved for gout, although there is burgeoning data suggesting that this strategy may have substantial merit.13 Additionally, there is limited evidence that adrenocorticotropic hormone (ACTH) may provide rapid pain relief when other available therapies are ineffective or contraindicated. However, ACTH studies have not provided robust trial designs, and drug costs remain substantial, thus limiting the widespread use of ACTH in acute gout.14,15 Anti-IL-1 agents and ACTH may both be considered as second-line options if first-line therapies are contraindicated or fail. Careful consideration should be given to AE profiles, patient preferences, and cost.

Acute gout care, especially in the context of comorbidities, has been identified as a critical treatment concern by an international panel of rheumatologists as part of the 3e (Evidence, Expertise, Exchange) Initiative. 16 However, regular clinical trial exclusion criteria have limited data necessary to guide treatment when comorbidities are present. Therefore, studies of acute gout treatment in the context of disease comorbidity represents a major unmet need in understanding and optimizing gout care.

Chronic Kidney Disease

Chronic kidney disease is common in gout; 20% of patients with gout have an estimated glomerular filtration rate (eGFR) of < 30 mL/min.2 Thus, CKD is an important consideration when deciding the best treatment for acute gout. The ACR recommendations do not provide specific guidance on NSAID use in CKD but suggest the potential option of tapering the dose as pain begins to resolve. There is mixed evidence that NSAIDs accelerate CKD progression with the best evidence for high-dose NSAID use.17 When prescribing the concomitant use of NSAIDs with other medications affecting kidney function, HCPs should consider CKD.

For colchicine, current labeling and evidence indicate that no dose adjustments are needed for stage 3 or better CKD (eGFR ≥ 60 mL/min) even among the elderly. 18,19 Although labeling indicates that a single unadjusted dose (0.6 mg) can be given once every 2 weeks for those with severe CKD (eGFR < 30 mL/min) or for those who are on dialysis, alternative therapies should be considered, as AEs increase with decreasing renal function.19 Colchicine should not be used in those with eGFR < 10 mL/min.20 All patients who have CKD and are treated with colchicine should be informed of the AEs and closely observed for signs of toxicity, including blood dyscrasias, neuromyopathy, emesis, or diarrhea.

Considering the potential complications for NSAIDs and colchicine, patients with CKD may be good candidates for glucocorticoid therapy, administered either systemically or as an intra-articular injection. Alternatively, second-line agents such as ACTH or IL-1 inhibition may be considered in such patients.

Hypertension

Hypertension is one of the most common comorbidities among patients with gout. It is important for HCP consideration when deciding treatment. Poorly controlled hypertension is a contraindication for both NSAIDs and systemic glucocorticoids. Patients with hypertension in the absence of significant renal impairment may be good candidates for colchicine.

Diabetes and Hyperlipidemia

Glucocorticoids should be avoided if possible in the setting of inadequately controlled type 2 DM (T2DM) or hyperlipidemia. Glucocorticoids exacerbate insulin resistance and stimulate glucose secretion from the liver. This can create substantial and sometimes dangerous fluctuations in circulating glucose concentrations. Additionally, glucocorticoids may increase serum triglycerides and low-density lipoprotein levels. Thus, patients with T2DM or hyperlipidemia may be good candidates for alternative treatments, such as colchicine or NSAIDs.

Cardiovascular Disease

Cardiovascular disease risk has been shown to increase with the use of COX-2 inhibitors. This risk may be present for all NSAIDs. Current FDA labeling suggests limiting NSAID and COX-2 inhibitor use in patients with a history of myocardial infarction (MI), congestive heart failure, or stroke. Given the potential impact on cardiovascular risk factors, including hypertension, T2DM, and hyperlipidemia, glucocorticoids may not be ideal for patients with known CVD or those at high risk.

Recent evidence has shown that colchicine use is associated with a lower risk of MI among patients with gout.21 These results, in addition to a proposed dual role of IL-1 in both gout and CVD, suggest that either colchicine or IL-1 inhibitors may be rational agents in the treatment of acute gout in the context of CVD.22

Hepatic Impairment and GI Bleeding

Patients with cirrhosis should avoid NSAID use due to the potential increased bleeding risk from underlying coagulopathy. Additionally, colchicine clearance may be reduced in patients with severe liver impairment, mandating close surveillance when this agent is used. If hepatic impairment is mild to moderate, judicious use of any of the first-line therapies may be appropriate.

Patients with GI bleeding or a history of peptic ulcer disease should avoid NSAID use because of increased bleeding risk. If an NSAID is used, proton pump inhibitors decrease the risk of NSAID-associated mucosal damage.

Colchicine is metabolized by the cytochrome P450 3A4 enzyme (CYP3A4) and is a substrate for P-glycoprotein (P-gp). Therefore, concomitant use of colchicine with potent inhibitors of CYP3A4 or P-gp should be avoided when possible. These agents include macrolide antibiotics (clarithromyocin), calcium channel blockers (verapamil and diltiazem), and cyclosporine (commonly used in transplant patients who are at high risk for gout). New evidence-based dosing recommendations indicate that no dose reduction is required with azithromyocin.23

Nonsteroidal anti-inflammatory drugs are contraindicated with the concomitant use of angiotensin-converting enzyme (ACE) inhibitors and/or diuretics. Prostaglandin production is decreased while using NSAIDs, resulting in increased constriction of afferent renal arterioles and decreased glomerular filtration pressure. This physiologic effect of NSAIDs can be exacerbated when used in combination with ACE inhibitors or diuretics, both of which can also reduce glomerular filtration pressures. Combination therapy with either ACE inhibitors or diuretics increases the risk for NSAID-mediated acute kidney injury. Additionally, NSAID use should be avoided in patients taking anticoagulants such as warfarin or heparin due to increased bleeding risk.

Diagnosis is a key component of proper treatment of acute gout. A gout diagnosis is usually made based on clinical signs and symptoms, including sudden onset of pain that peaks within 24 hours, past history of acute self-limited attacks of arthritis, first MTP involvement, and an elevated sUA. However, not all these factors must be present. In a study conducted by Janssens and colleagues, these factors plus additional demographics had a sensitivity of 90% and specificity of 65% when compared with crystal diagnosis.24 However, a normal sUA level does not exclude gout as a diagnosis due to the uricosuric effect of the inflammatory process.25 In fact, one observational cohort recorded an average sUA decrease from baseline of 2 mg/dL during an acute gout attack. 26

Alternative diagnoses, including septic arthritis, should be considered, particularly in the context of treatment failure (< 50% reduction in pain) within the first 24 to 48 hours. A definitive diagnosis is made by identifying negatively birefringent crystals in the synovial fluid of the affected joint (using polarized microscopy) with negative cultures. In the absence of crystal confirmation, there is an emerging role for imaging in gout diagnosis, including the use of ultrasound and dual-energy computed tomography.27

During treatment for acute gout attacks, urate-lowering therapy that was initiated before the attack should not be discontinued.28 There is no evidence to suggest that current urate lowering has any AEs during attacks. However, removing treatment may increase sUA levels, precipitating attacks in other joints by “destabilizing” crystals still present. Current recommendations also state that urate-lowering therapy may be started during an attack despite traditionally being deferred until the attack has resolved. 28 In a randomized trial comparing a group starting allopurinol 300 mg during an attack vs a placebo group (with all patients receiving anti-inflammatory treatment for the acute attack), there was no difference in pain outcomes. 29 Regardless of the chosen timing, lowering and maintaining sUA ≤ 6.0 mg/dL is the primary method for minimizing long-term risk of gout attacks.28

Health care providers should discuss with patients the likely need for indefinite urate – lowering therapy while noting that attacks related to therapy initiation are relatively common.30 Current guidelines recommend starting urate-lowering therapy in low doses (≤ 100 mg/d for allopurinol) and titrating to achieve and maintain the target sUA level. Along with the judicious use of anti-inflammatory prophylaxis, this may minimize attacks related to therapy initiation.3,28 By lowering and maintaining sUA below the target level, monosodium urate crystals will dissolve, thereby eliminating the major inciting factor of acute attacks.

Other day-to-day triggers such as alcohol, meat or seafood consumption, and dehydration exist for some patients with gout. Patients should be informed of these inciting factors, as they could potentially be avoided, reducing the risk of future gout attacks. It is important to recognize, however, that dietary or behavioral interventions have generally yielded only modest sUA reductions. For the majority of patients, therefore, reduction and maintenance of sUA ≤ 6.0 mg/dL requires pharmacologic intervention.

Gout attacks should be treated immediately with pharmacologic treatment when contraindications are absent. First-line treatment options include NSAIDs, colchicine, and systemic glucocorticoids. Use of these modalities can be complicated because of comorbidity and concomitant medication use that is prevalent among patients with gout. Comorbidities commonly limiting treatment choice include hypertension (NSAIDs, glucocorticoids), CKD (NSAIDS, colchicine), CVD (NSAIDs, COX-2 inhibitors, glucocorticoids), T2DM (glucocorticoids), and liver disease (NSAIDs, colchicine). Careful consideration must be given to these comorbidities and contraindications as well as patient preferences.

Author disclosures

The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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Gout, part 2. Treatment – articles from the specialists of the clinic “Mother and Child”

Non-drug treatment of gout

In the treatment of gout, non-drug methods, that is, non-drug therapy, come to the fore. And the first thing the patient should be aware of is the need to follow a low-purine diet . This is an item of paramount importance in prescriptions, which significantly increases the chances of successful treatment of gout. The level of uric acid in our body directly depends on the amount of protein that comes from food.

• Therefore, products containing a lot of protein of vegetable and animal origin in the period of arthritis must be excluded , canned meat and fish, meat, fish, mushroom broths.
• Preference should be given to vegetables, fruits, dairy products, cereals. Citrus fruits, cucumbers are very good at removing uric acid.
• Orange fruits and vegetables should be limited. Avoid spinach, sorrel. From fruits and berries NOT shown: plums, raspberries, figs, grapes.
• In addition, a patient with gout should drink 2-2.5 liters of fluid per day to prevent crystallization of uric acid in the kidneys. Fruit drinks, compotes, citrus juices, cucumber juice, mineral water (alkaline), green tea are especially useful. Grain coffee for the duration of the attack is better to exclude. The drinking regimen for patients with concomitant cardiovascular diseases must be agreed with their cardiologist.
• In the interictal period, dietary advice allows the patient to gradually introduce meat and fish into his diet. Cooking method – boiled, baked, steamed. Meat and fish broths, frying, stewing are not recommended. Meat and fish are administered first 2 times a week, then every other day, 100-150 g / day.
• Special relationship with gout to alcoholic beverages. Alcohol must be avoided, especially beer, red wine and spirits. Alcohol practically blocks the excretion of uric acid by the kidneys, which contributes to its increase in the blood.

The drug treatment of gout can be divided into two periods: this is the treatment of an acute attack (arthritic relief) and the treatment in the period between attacks .

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for acute gouty arthritis. They relieve pain well, reduce the activity of inflammation and have an antipyretic effect. Intramuscular injections, oral forms (tablets, capsules, powders), rectal suppositories are used. When prescribing these drugs, the doctor must weigh the benefit / risk ratio for each individual patient and choose the most effective and safe remedy in his opinion. In some cases, as mentioned above, a patient with gout has a number of other diseases (diabetes mellitus, hypertension, chronic heart failure, etc.) that require a differentiated approach when choosing NSAIDs.

With insufficient effect from NSAIDs, glucocorticosteroids (GCS) can be used to stop persistent arthritis in a protracted gouty attack. These are drugs related to steroid hormones. They have a pronounced anti-inflammatory effect. They are used for injection into the inflamed joint, intramuscularly, intravenous infusion (drip administration), less often – tablet forms. These drugs are prescribed in a short course and, as a rule, with a pronounced positive effect.

When glucocorticosteroids (prednisolone, methylprednisolone, dexamethasone, hydrocortisone, betamethasone, etc.) are included in the treatment regimen, observation by a rheumatologist, monitoring of blood pressure, blood glucose and other indicators is required. Self-administration of corticosteroids by patients without consulting a doctor is excluded in order to avoid serious consequences from improper use.

Colchicine also relieves gout attacks, has a good anti-inflammatory effect, reduces the formation of uric acid. The treatment regimen is selected by the doctor, assessing the patient’s condition, the presence of concomitant diseases, age, etc.

After the successful treatment of acute arthritis , we should all understand that the treatment of gout does not end there. And it would be a mistake to celebrate the victory over the disease too soon. Unfortunately, in some cases, such tactics of the doctor (or the patient’s unwillingness to continue treatment) take place. In the absence of treatment in the interictal period, there is a high risk of recurrence of arthritis and the development of persistent chronic gout with complications. We are talking about continuing to follow a low-purine diet and taking the so-called basic drugs that control the level of uric acid in the blood. And the most common of them is allopurinol, a drug with a good safety profile and a good benefit/risk ratio. Allopurinol reduces the formation of uric acid in the body, and also improves its excretion by the kidneys. The dose is selected by a rheumatologist, recommending regularly (at the initial stage, at least once a month) to examine the level of uric acid in the blood to adjust the dose of allopurinol. The most common mistake of a doctor (often a non-specialist) is the appointment of allopurinol in the acute period. The drug itself can provoke the development of arthritis. Therefore, the start of taking the drug should be recommended in the interictal period, accompanied by anti-inflammatory treatment for a short period of time .

Gout prevention

Compliance with a diet with a moderate content of meat products, restriction of animal fats, avoidance of alcohol or its moderate consumption, fight against excess body weight (low-calorie diet, adequate physical activity) are effective measures to prevent gout and often accompanying metabolic syndrome.

And with the development of symptoms of the disease, the patient should know that in order to improve the long-term prognosis, to maintain a good quality of life for many years, adequate treatment should be started on time under the guidance of a rheumatologist. Gout is a chronic disease that requires constant attention, revision of lifestyle, eating habits, attitude to alcohol. Often, a patient with gout is treated by a rheumatologist together with urologists, nephrologists (with kidney damage), cardiologists (correction of treatment of arterial hypertension, heart failure, exclusion of certain diuretics, replacement of aspirin with other antiplatelet agents, etc. ), endocrinologists ( treatment of diabetes mellitus and obesity), surgeons (removal of tophi, treatment of complicated forms).

Long-term remission for gout is the goal that the patient should strive for together with his doctor. With the right comprehensive approach to treatment, this goal becomes more than realistic.

Treatment of gout. Treatment of an acute attack. Uric acid.

Treatment of gout is to relieve inflammation and slowly lower uric acid levels. Gout is a well-known and well-studied disease associated with acute inflammation of the joints of the lower and upper extremities of a person, characterized by elevated levels of uric acid, followed by crystallization and precipitation. Hyperuricemia is when the concentration of uric acid in serum or plasma exceeds 6.8 mg/dl (approximately 400 micromoles/l). It should be noted that this level of uric acid is its approximate limit when it can crystallize.

Hyperuricemia (elevated uric acid) is a necessary but not sufficient prerequisite for the development of gout (direct sodium monourate crystal deposits). Physicians and patients should distinguish hyperuricemia from gout. Because Most people with hyperuricemia never experience the clinical manifestations associated with the deposition of urate crystals, namely an attack of gout.

Contents

Brief description of the disease

The disease itself with its clinical features has been described in the literature for more than two millennia, with its interesting observations and studies. But it wasn’t until the second half of the 20th century that evidence emerged that the cause of gout included the deposition of uric acid (sodium monourate) crystals. The key point is the introduction into clinical practice of microscopes using polarized light, which ensured the identification of urate crystals in the synovial fluid of the joints (intra-articular fluid).

Thus, an end was put to the mechanism of this disease and the ambiguous relationship between hyperuricemia and gout was resolved. Further study of this disease has expanded the understanding of the molecular pathophysiology of inflammation in gout, thereby helping to create effective drugs for the treatment of such a common and well-known disease.

Further development of drugs capable of suppressing acute inflammation and eliminating elevated levels of uric acid in the body, provided the opportunity to completely eliminate previously destructive effects in chronic and acute inflammatory processes.

Although modern drugs have a beneficial effect on the course of gout in most people, nevertheless, this disease remains an urgent problem today, and often with unsatisfactory clinical outcomes, despite successful attempts at treatment. This is very common in poorly trained patients, or in patients who do not follow our guidelines exactly.

NETWORK OF BIOMEDICAL CENTERS IN COMUNIDAD VALENCIANA, ESPAÑA-ASCIRES

What is the treatment for gout? What to take for an acute attack of gout?

NSAIDs. Non-steroidal anti-inflammatory drugs.

First aid for acute gout flare with strong oral NSAIDs such as naproxen (500 mg twice daily) or indomethacin (50 mg three times daily) as a good alternative to glucocorticoids for the treatment of a gout flare. It is especially effective for young patients who are less than 60 years of age, without renal or cardiovascular comorbidities or active gastrointestinal diseases.

Non-selective NSAIDs of all types are inexpensive, easy to obtain over the counter (some over the counter), and in our experience are as effective and safe as other drugs in treating a gout flare. Other drugs in this class that can be used are ibuprofen (800 mg three times daily), diclofenac (50 mg twice daily), meloxicam (15 mg daily) and celecoxib (200 mg twice a day).

[su_highlight]-Remember! Do not take more than one NSAID at the same time! Those. You can’t take Ibuprofen and Diclofenac at the same time just because it helps you.[/su_highlight]

Anti-inflammatory drugs are most effective when treatment is started within the first 48 hours of symptom onset. The dose may be reduced after a significant reduction in symptoms, but the frequency of administration should be maintained for several more days to achieve the optimal anti-inflammatory effect.

Celecoxib , a selective cyclooxygenase (COX)-2 inhibitor, is a very good alternative to ibuprofens, meloxicam, diclofenac (a non-selective NSAID) for gout flares, a single dose of celecoxib at a dose of 200 mg, for no more than two weeks. In practice, we often use 200mg twice a day, which is the maximum dose recommended for rheumatoid arthritis.

Any NSAID (ibuprofen) can be discontinued two to three days after clinical signs have completely disappeared. Typically, the total duration of naproxen therapy for a gout flare is five to seven days. It is likely that the clinical picture will be shorter in patients who are treated within the first 24 hours after the onset of symptoms.

Colchicine / Colchicina / Colchimax / Colchicine

For me, this is the ideal alternative to glucocorticoids (pridnisone) or NSAIDs (ibuprofen) is colchicine has actually shown to be effective compared to other drugs when taken within 24 hours of a gout flare. Colchicine should be taken at 1 mg once daily until the outbreak resolves. In some countries, colchicine is available as a 0.5 mg tablet instead of a 0.6 mg tablet. The maximum dose is 2 mg per day according to the new treatment protocols. Previously used up to 6 mg per day, but this is an old regimen, and it is no longer used due to the potential for side effects.

It is worth noting the toxicity of the drug if used improperly. Therefore, before taking, we recommend that you consult your doctor. The main side effect of colchicine is diarrhea and vomiting. Patients and professionals should pay very close attention to the interaction of colchicine with the following drugs: macrolide antibiotics (azithromycin, clarithromycin, erythromycin), cyclosporine, tacrolimus, amiodarone, quinidine, azole antifungals (ketoconazole), verapamil, CYP3A4 inhibitors (HIV therapy, ritonavir , cobicistat).

Colchicine is particularly useful for patients already on allopurinol who are in the early phase of a gout flare. Often we meet patients who are familiar with their disease, but have not heard anything about colchicine.

If you have any questions, make an appointment for a consultation

Does your lifestyle affect the level of uric acid? Eliminate the following foods from your diet… Find out in this article.

There used to be a so-called demographic profile of gout that fit the “classic” example: a man in his 30s and 60s who suffers from gout attacks who is also likely to be obese, hypertensive (high blood pressure) and heavy alcohol drinker .

But there are “non-classical” risk groups that are becoming more common, and these patient groups are very different from the “classic profile”. This includes older patients, organ transplant patients, people taking diuretics, cancer patients, use of drugs such as cyclosporine or tacrolimus (a calcineurin inhibitor), and unfortunately the proportion of women with gout has increased.

What are the clinical manifestations of a gout flare?

Persistent and elevated levels of uric acid in the body (hyperuricemia) is a common biochemical abnormality resulting from excessive production of uric acid (urate) or impaired excretion of uric acid by the kidneys .

Therefore, hyperuricemia (saturation of blood serum with urate) is always observed in all patients with gout during the period of their illness. However, most people with hyperuricemia never experience the clinical manifestations of gout associated with the deposition of urate crystals.

Clinical manifestations of gout include:

• Recurrent flare-ups of inflammatory arthritis (gout flare). Most often in autumn and spring.
• Do you have a sharp inflammation of the joint of the toe on your right foot? Read below for what it is.
• This is a severe and sharp pain in the joint, redness, the joint “burns”, swelling, inability to walk. And usually the patient says that there was no injury! The picture itself usually appears within 12-24 hours, which is quite fast in itself and is typical for this attack. Complete resolution of the earliest outbreaks almost always occurs within a few days to a few weeks, even in untreated people.
• Gout flares are twice as likely to occur during the night and early morning than during the day. Patients often say that they cannot stand on their feet in the morning, because, according to their words, “the knee suddenly became inflamed overnight, while yesterday everything was fine, and I didn’t hit my foot anywhere.”
• Damage to the lower extremities. At least most initial outbreaks affect one joint, most commonly at the base of the big toe (the first metatarsophalangeal joint, known as gout) or the knee.
• Intermittent joint problem, chronic arthropathy.

Can gout affect the joints of the fingers and elbows? Yes maybe!

Multi-articular gout flares – The multi-articular pattern is an initial presentation in a small number of patients with gout, but with increasing frequency in subsequent flares. Multi-joint symptoms are especially common in the advanced stages of untreated gout, when multiple recurrences are common. Fingers, elbows, upper jaw.

Signs of inflammation extending beyond the joint due to arthritis in several adjacent joints or tenosynovitis. Unusual involvement of the vertebral joints and sacroiliac joints, where gout may occur much less frequently and may cause diagnostic confusion. The most commonly affected area is the lumbar spine. However, most proven cases of gout, manifesting as acute or chronic back pain, have been associated with gastric involvement. There may also be neurological signs and symptoms.

Accumulation of uric acid crystals in the form of external deposits.

Tophi are characteristic accumulations of solid urate, accompanied by chronic inflammatory and often destructive changes in the connective tissue. Tophi are often visible and can be touched and felt (palpated) and may be present on the ears or in soft tissues, including articular structures, tendons, or periarticular bursae. Tofus (tophs) usually do not hurt and are solid in structure. They are visible on the skin, have a slightly yellow or white color. On the ear, they are found in the form of balls, and do not transmit light.

[su_spoiler title=”Note to Medical Students and Physicians” style=”fancy”]-Chronic inflammation extending beyond one joint with uric acid deposition resembles and is similar to dactylitis seen in other diseases such as psoriatic arthritis, other spondyloarthritis and sarcoidosis. The expansive and destructive changes associated with gouty gout can be mistaken for osteomyelitis and sometimes lead to erroneous amputation of the fingers involved.[/su_spoiler]

Deposition of uric acid crystals in the kidneys. Nephrolithiasis.

Uric acid stones account for 5 to 10 percent of all kidney stones worldwide; however, they make up 40 percent or more of the stones in areas with hot and dry climates. The most important biochemical risk factor for the development of urolithiasis nephrolithiasis is a persistently low urine pH. And the low volume of urine (with a high concentration of uric acid in the urine) and the acidic pH of the urine promote the conversion of the relatively soluble urate salt into insoluble uric acid.

Patients usually have an attack of renal colic, complain of acute pain in the right or left side. Computed tomography (CT) without contrast/dye usually reveals the presence of a stone. Many patients are advised to confirm the diagnosis with a chemical analysis of the stone. It is worth noting that in conventional radiographs, uric acid stones are transparent and almost impossible to see.

Chronic nephropathy, which in gouty patients most often occurs due to concomitant conditions.

Chronic urate nephropathy is the last stage of chronic kidney disease in chronic gout, caused by the deposition of uric acid crystals in the kidneys (medullary interstitium). The crystals cause a chronic inflammatory response similar to that seen with tophi formation in other parts of the body, which eventually leads to interstitial fibrosis and chronic kidney disease.

The clinical stages of the disease (“Gout Flares”, “Recurrent Gout Flares”, “Chronic Gout”) occur sequentially, with a corresponding clinical severity that often coincides with the frequency of gout flares. Therefore, treatment with uric acid-lowering (antihyperuricemic) drugs is deterrent, and provides effective recovery of the patient if the urate saturation level does not rise above <6 mg/dL or 357 micromoles/L.[su_divider]

High level of uric acid. How and with what drugs to control a chronic disease. Where to start?

Heavy drinking and alkalinization of the urine (potassium citrate) can cause clear uric acid stones to dissolve. Either potassium citrate or potassium bicarbonate can be taken with a typical dose of 30 to 80 mEq/day. This regimen can dissolve already existing pure uric acid stones and prevent new stones from forming.

For us, urine alkalinization with potassium citrate salts is currently the preferred solution, as sodium loading with sodium citrate or sodium bicarbonate can increase calcium excretion and promote calcium stone formation in some patients. Alkalinization is carried out so that the pH of the urine is between 6.5 and 7. We also recommend that patients drink enough liquid so that the volume of urine within 24 hours is at least two liters.

Many patients are familiar with Allopurinol and Probenecid (Probalan, a uricosuric agent). These are well-known, proven and old drugs that have proven themselves well and have demonstrated their effectiveness.

If uric acid kidney stones cannot be prevented despite urine alkalinization (or who cannot tolerate additional alkali) and higher fluid intake, we recommend treatment with a xanthine oxidase inhibitor (Allopurinol). These patients usually have hyperuricosuria (greater than 1000 mg/day [6 mmol/day]), but xanthine oxidase inhibitors are warranted even in patients with recurrent stones and lower levels of urinary uric acid excretion.

Allopurinol / Allopurinol / Zyloric

It is worth noting that Allopurinol is used for patients with elevated uric acid when there is no acute attack of gout. Otherwise, the effect will be the opposite.

This is a truly time-tested product. Very well known among patients, often used in clinical practice for chronic uric acid control, easy dosage and availability.

From clinical practice, patients often turn to us when a gout attack has already manifested itself. People, without knowing it and through no fault of their own, begin to take allopurinol, after which the attack worsens even more. This drug is very effective in preventing seizures when taken on a continuous basis, even when there are no prerequisites for an aggravation of the clinical picture.

Febuxostat / Febuxostat / Adenuric / Uloric

One of the newest and most effective uric acid control drugs. Replaced allopurinol. Indeed, it is used in clinical practice, where allopurinol is not effective enough. Febuxostat is actively replacing allopurinol, but in February 2019, the Food and Drug Administration (FDA) issued a warning about the increased risk of death from Uloric (febuxostat) compared to allopurinol.

This conclusion is based on a detailed review of the results of a safety clinical trial that found an increased risk of all-cause CV mortality with Uloric. Patients with gout and established cardiovascular disease who received febuxostat had a higher rate of death from cardiovascular disease compared with patients who received allopurinol.

A new warning about this risk is now added to the Uloric/Adenuric prescribing information (including the boxed warning). Today, new guidance limits the previously approved use of Febuxostat to patients. Febuxostat should only be prescribed to patients who have an inadequate response to the maximum dose of allopurinol, who cannot tolerate allopurinol, or for whom treatment with allopurinol is not recommended, and who do not have cardiovascular disease.

Probenecid / Probalan / Probenecid

Reduces the reabsorption of uric acid in the renal tubules, thereby increasing its excretion, reducing the deposition of urates. But to date, the main therapeutic indication for the use of probenecid is to support the level of penicillinemia in the treatment of diseases.

Probenecid reduces the excretion of penicillins by increasing and prolonging the plasma levels of penicillin, ampicillin, methacillin, oxacillin, cloxacillin, or nafcillin.

Also used to prevent renal toxicity in cisplatin chemotherapy. In the treatment of syphilis, it maintains an effective level of antibiotics. The use of this drug in conjunction with colchicine is useful in an acute attack of gout. However, it is strictly contraindicated in patients with hepatic and renal insufficiency.

Rasburicase / Rasburicase

/ Elitek / Fasturtec /

The drug is exclusively used intravenously for the control of uric acid levels in oncology, is released only for hospital use. Requires strict dosing. High probability of side effects, up to an anaphylactic reaction. Therefore, this application is strictly regulated.

This drug is interesting for very high levels of uric acid in the body, which is not even associated with metabolism, but with massive cell destruction. This is when chemotherapy is used to destroy the tumor, and when the cancer cells are destroyed, their toxic contents are released into the human body.

By the way, one of the basic principles of the use of chemotherapy is that you cannot immediately destroy one kilogram of cancer cells, because the body simply cannot survive such a toxic release of their destruction.

Glucocorticoids/ Glucocorticoides.

We now rarely use oral glucocorticoids (prednisone, prednisolone), especially in situations where the patient is not a candidate for intra-articular corticoid injections. There are many patients who have contraindications to the use of non-steroidal anti-inflammatory drugs (ibuprofen, naproxen), in which case we can prescribe corticoids for them.

The initial dose of prednisone or prednisolone is 30 to 40 mg per day.