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.
Comorbidities
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.