Allopurinol and febuxostat are similarly effective in controlling flares in patients with gout, including those with stage 3 chronic kidney disease (CKD), according to trial results published in the New England Journal of Medicine.

In double-blind CSP594 Comparative Effectiveness in Gout: Allopurinol vs Febuxostat trial (ClinicalTrials.gov identifier: NCT02579096), investigators randomly assigned 940 patients with hyperuricemia to receive allopurinol or febuxostat at titrated doses to achieve a serum urate target of 6mg/dL or lower (or 5mg/dL or lower if tophi were present). Approximately a third of patients in both groups had stage 3 CKD (30-59 mL/min/1.73 m² using the Modification of Diet in Renal Disease study formula for estimated glomerular filtration rate). The allopurinol and febuxostat groups received daily doses of 100 and 40mg, respectively, to start, then therapies were titrated until attainment of target uric acid levels or maximal dose. Patients also received guideline-directed anti-inflammatory prophylaxis with colchicine, nonsteroidal anti-inflammatory drugs, or glucocorticoids. After the maintenance phase, no study drug dose adjustments were allowed, and all anti-inflammatory treatments were discontinued except in the event of gout flare.

Results showed that 36.5% of the allopurinol group and 43.5% of the febuxostat group experienced the primary outcome of 1 or more gout flares during the observation phase; a 7% difference that met a criterion for noninferiority, James R. O’Dell, MD, of Veterans Affairs (VA) Nebraska-Western Iowa Health Care System in Omaha, Nebraska, and colleagues reported. Among patients with stage 3 CKD, allopurinol also proved noninferior to febuxostat with 31.9% vs 45.3% experiencing a gout flare, respectively, the investigators reported.

In both the allopurinol and febuxostat groups, 80% of patients, including those with stage 3 CKD, achieved and maintained target serum urate levels at 1 year.

“Our randomized double-blind trial demonstrates that allopurinol, when dosed appropriately as part of a titrate-to-target strategy, is noninferior to febuxostat with respect to flares of gout,” Dr O’Dell’s team wrote.

In 2019, the FDA issued a boxed warning concerning the cardiovascular safety of febuxostat based on results of the CARES (Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout) trial. The 2020 FAST trial (Febuxostat versus Allopurinol Streamlined Trial), however, showed no increased risk for cardiovascular events. In the current study, the investigators found no evidence that febuxostat increases cardiovascular morbidity or overall mortality compared with allopurinol. Serious adverse events (26.7% vs 26.1%), including cardiovascular events (8.1% vs 6.8%) and death (8 patients in each group), occurred in comparable proportions of the allopurinol and febuxostat arms, respectively. Dr O’Dell and colleagues suggested that the nearly ubiquitous use of colchicine in the early phases of the trial might have mitigated cardiovascular risks.

Dr O’Dell’s team made other observations that also warrant additional research. Hospitalization for heart failure was numerically higher among patients treated with allopurinol (23 vs 10 hospitalizations). A post hoc analysis showed that acute kidney injury occurred in 15 allopurinol-treated patients compared with 4 febuxostat-treated patients who had stage 3 CKD. Most AKI events were related to volume depletion or congestive heart failure, the investigators noted. All but 3 AKI events were transient.

Reference

O’Dell JR, Brophy MT, Pillinger MH, et al. Comparative effectiveness of allopurinol and febuxostat in gout management. N Engl J Med. Published online February 3, 2022. doi:10.1056/EVIDoa2100028

Benzbromarone may reduce the risk of developing chronic kidney disease (CKD) among adults with asymptomatic hyperuricemia, new study findings suggest.

Using the 2003 to 2015 National Health Insurance Research Database in Taiwan, investigators propensity score matched 9107 benzbromarone users to 4554 allopurinol users by age, sex, and comorbidities. All patients had asymptomatic hyperuricemia, defined as the use of urate-lowering drugs without history of gout flares. Patients were free of gouty disorders and CKD at baseline. The cohort had a mean age of 56 years; 71% were male.

The benzbromarone group had a lower incidence of newly diagnosed CKD compared with the allopurinol group (1.18 vs 1.99 per 100 person-years).

Older age, male sex, and pre-existing diabetes and hypertension were each significantly associated with higher risk of CKD.

A Cox proportional hazards regression analysis showed that the benzbromarone group had a significant 41% lower risk of CKD diagnosis compared with the allopurinol group, Chiu-Shong Liu, MD, China Medical University in Taichung, Taiwan, and colleagues reported in the European Journal of Internal Medicine. Regardless of the cumulative defined daily drug dose, benzbromarone appeared more protective than allopurinol.

Benzbromarone may better reduce serum uric acid levels compared with allopurinol, according to Dr Liu’s team. The drug is an inhibitor of urate transporter 1 (URAT1) in the proximal tubule. The investigators could not evaluate serum uric acid levels, serum creatinine levels, albuminuria, or estimated glomerular filtration rate before or after drug use, which is a study limitation.

Patients with renal impairment or urolithiasis should avoid using benzbromarone, the investigators noted. The drug has been taken off the market in many countries due to the potential for hepatotoxicity.

Dr Liu’s team pointed out that in Taiwan urate-lowering treatment is considered when patients have high serum uric acid levels. These include individuals with serum uric acid levels of 9 mg/dL or more with comorbidities but no evidence of gouty arthritis, gouty tophi, or urolithiasis and those with serum uric acid levels of 10 mg/dL or more and no comorbidities. CKD risk might be higher for these patients.

“If the above approach is how physicians prescribe the urate-lowering drugs for persons included in our study, then the study findings might only apply to persons who have quite high serum level of uric acid,” Dr Liu and colleagues stated.

Reference

Lai SW, Liao KF, Kuo YH, Hwang BF, Liu CS. Comparison of benzbromarone and allopurinol on the risk of chronic kidney disease in people with asymptomatic hyperuricemia. Eur J Intern Med. Published online April 29, 2023. doi:10.1016/j.ejim.2023.04.025

The findings are based on analysis of data from Explorys Inc, a validated, multicenter and research platform database of more than 360 hospitals from 26 different US health care systems from 1999 to September 2022.

Eligible participants were aged over 18 years. Those with a history of familial adenomatous polyposis, a family history of CRC, and inflammatory bowel disease were excluded.

Multivariate regression analysis was used to calculate the risk for CRC and account for potential cofounders, including male sex, smoking history, alcoholism, obesity, type 2 diabetes, and those diagnosed with CTG. A 2-sided P value less than .05 was considered statistically significant.

A total of 70,177,200 individuals were included in the final analysis; 234,840 had CRC and 69,942,360 had no CRC. Type 2 diabetes (28.57% vs 7.90%), smokers (10.98% vs 5.33%), obesity (18.71% vs 7.59%), alcoholism (3.13% vs 1.53%), and patients who have had a diagnosis of CTG (0.08% vs 0.01%) were more common in the CRC group compared with those without CRC, respectively.

According to multivariate regression analysis, the risk for CRC was calculated for the male sex (odds ratio [OR], 1.02; 95% CI, 1.01-1.03), smokers (OR, 1.54; 95% CI, 1.52-1.56), alcoholism (OR, 1.40; 95% CI, 1.37-1.43), obesity (OR, 1.52; 95% CI, 1.50-1.54), type 2 diabetes (OR, 3.53; 95% CI, 3.50-3.57), and a diagnosis of CTG (OR, 1.40; 95% CI, 2.48-3.23).

“Uric acid is likely 1 of the culprits of this association, as it leads to increased production of reactive oxygen species and promotes tumorigenesis,” the researchers wrote. “Further research is required to assess the prevalence of colon cancer in patients with gout and serum uric acid that is <7 mg/dL. This will promote additional discussion about tighter control of serum uric acid levels in this population in order to decrease the overall risk of colon cancer.”

The findings are based on analysis of data from Explorys Inc, a validated, multicenter and research platform database of more than 360 hospitals from 26 different US health care systems from 1999 to September 2022.

Eligible participants were aged over 18 years. Those with a history of familial adenomatous polyposis, a family history of CRC, and inflammatory bowel disease were excluded.

Multivariate regression analysis was used to calculate the risk for CRC and account for potential cofounders, including male sex, smoking history, alcoholism, obesity, type 2 diabetes, and those diagnosed with CTG. A 2-sided P value less than .05 was considered statistically significant.

A total of 70,177,200 individuals were included in the final analysis; 234,840 had CRC and 69,942,360 had no CRC. Type 2 diabetes (28.57% vs 7.90%), smokers (10.98% vs 5.33%), obesity (18.71% vs 7.59%), alcoholism (3.13% vs 1.53%), and patients who have had a diagnosis of CTG (0.08% vs 0.01%) were more common in the CRC group compared with those without CRC, respectively.

According to multivariate regression analysis, the risk for CRC was calculated for the male sex (odds ratio [OR], 1.02; 95% CI, 1.01-1.03), smokers (OR, 1.54; 95% CI, 1.52-1.56), alcoholism (OR, 1.40; 95% CI, 1.37-1.43), obesity (OR, 1.52; 95% CI, 1.50-1.54), type 2 diabetes (OR, 3.53; 95% CI, 3.50-3.57), and a diagnosis of CTG (OR, 1.40; 95% CI, 2.48-3.23).

“Uric acid is likely 1 of the culprits of this association, as it leads to increased production of reactive oxygen species and promotes tumorigenesis,” the researchers wrote. “Further research is required to assess the prevalence of colon cancer in patients with gout and serum uric acid that is less than 7 mg/dL. This will promote additional discussion about tighter control of serum uric acid levels in this population in order to decrease the overall risk of colon cancer.”

The large colchicine price increase in 2010 led to a decrease in its use. Hospital and health care visits for gout have increased since then.

Colchicine is an anti-inflammatory drug used to treat and prevent acute gout flares. These recent trends are consistent with poorer disease control, Zirui Song, MD, PhD, of Harvard Medical School in Boston, Massachusetts, and colleagues reported in JAMA Internal Medicine. Price increases in medications that have few or no substitutes could have adverse economic and clinical consequences, they warned.

The FDA discontinued lower-priced versions of colchicine in 2010 after it granted market exclusivity to Colcrys for 3 years. The mean price per prescription of colchicine increased from $11.25 in 2009 to $190.49 in 2011. Average out-of-pocket costs increased from $7.37 to $39.49. These costs remained high through 2019.

From 2007-2010 to 2011-2019, mean colchicine use declined significantly by 9.6 pills per patients in adjusted analyses, while allopurinol use rose significantly by 33.1 pills per patient and oral corticosteroid use by 1.5 pills per patient, the investigators reported.

Emergency department visits for gout significantly increased by 40% over the decade or by 0.05 visits per patient. Rheumatology visits for gout likewise increased 11% or 0.02 visits per patient.

“These findings,” Dr Song’s team wrote, “suggest that as gout flares became more expensive to treat, patients and clinicians may have been more aggressive in preventing such flares by increasing allopurinol use; that is, when the price of a treatment rises, prevention may receive more attention, which is beneficial.”

The data were based on a large cohort of patients with gout who had employer-sponsored insurance from 2007 through 2019.

The study was observational, so correlation does not imply causation. The investigators could not rule out secular trends such as changes in the economy and health care or account for gout severity.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Ly DP, Giuriato MA, Song Z. Changes in prescription drug and health care use over 9 years after the large drug price increase for colchicine. JAMA Intern Med. Published online May 8, 2023. doi:10.1001/jamainternmed.2023.0898

Dapagliflozin reduces the risk of adverse cardiovascular outcomes outcomes in patients with heart failure, whether or not they also have gout. The sodium glucose cotransporter 2 inhibitor also reduces the need for uric acid-lowering therapy.

In a post hoc analysis of data from the DAPA-HF and DELIVER trials, 1117 of 11,005 patients with heart failure (10.1%) had a history of gout. Gout was present in 10.3% and 10.1% of patients with a left ventricular ejection fraction up to 40% and more than 40%, respectively. In the group with and without gout, 59.7% and 43.8% also had stage 3 or higher chronic kidney disease. The gout group had more men, higher body mass index, and greater comorbidity burden. The patients with gout also were more commonly treated with loop diuretics.

The primary outcome of worsening heart failure or cardiovascular death occurred at a significantly higher rate among patients with vs without gout: 14.7 vs 10.5 per 100 person-years.The gout group had a significant 15% higher risk of the primary outcome.

Dapagliflozin 10mg once daily reduced the risk of the primary outcome by 16% and 21% among patients with and without gout, respectively, compared with placebo, John J. V. McMurray, MD, of British Heart Foundation Cardiovascular Research Centre, University of Glasgow in the United Kingdom, and colleagues reported in JAMA Cardiology.

Baseline use of uric acid-lowering therapy or colchicine was 63.7% and 7.8%, respectively, among the group with and without gout. Among a subset of patients naïve to these therapies at baseline, dapagliflozin reduced the risk of initiating uric acid-lowering therapy by 50% and 57% and colchicine by 48% and 40% in the group with and without gout, respectively, compared with placebo.

“These data underline the substantial and clinically important benefits of dapagliflozin in [heart failure], irrespective of gout status,” according to Dr McMurray’s team.

“Dapagliflozin reduced the initiation of medications used to reduce urate level or to treat gout flares, representing a meaningful additional clinical benefit of dapagliflozin in patients with [heart failure].”

Disclosure: The DAPA-HF and DELIVER trials were funded by AstraZeneca. Please see the original reference for a full list of disclosures.

Reference

Butt JH, Docherty KF, Claggett BL, et al. Association of dapagliflozin use with clinical outcomes and the introduction of uric acid-lowering therapy and colchicine in patients with heart failure with and without gout: A patient-level pooled meta-analysis of DAPA-HF and DELIVER. JAMA Cardiol. Published online February 22, 2023. doi:10.1001/jamacardio.2022.5608

Among second-line type 2 diabetes treatments, sodium-glucose cotransporter type 2 inhibitors (SGLT2i) carry the lowest risks for gout, according to new research presented at the 2023 EULAR meeting.

Investigators identified metformin-treated patients with type 2 diabetes proceeding to second-line therapy among residents of British Columbia, Canada from Jan 2014 to June 2022. In analyses of 27,791 patients, SGLT2i was significantly associated with a 46% lower risk of a gout diagnosis (and gout drug prescription) compared with dipeptidyl peptidase 4 inhibitors (DPP4i), Chio Yokose, MD, MSC, of Yokose Massachusetts General Hospital in Boston, Massachusetts, and colleagues reported. In analyses of 19,875 patients, SGLT2i was significantly associated with a 61% lower risk of gout compared with glucagon-like peptide-1 receptor agonist (GLP1RA). In analyses of 71,625 patients, SGLT2i was significantly associated with a 39% lower risk of gout compared with sulfonylureas. Results were consistent across age, sex, and baseline diuretic use.

As expected, SGLT2i initiators carried higher risks of genital infection among the second-line treatments.

“Along with its known urate-lowering, as well as cardiovascular and survival benefits, SGLT2i could reduce risk of incident gout substantially for diabetes patients who need [a] second-line agent after metformin,” Dr Yokose’s team wrote in a study abstract.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Yokose C, Mccormick N, Lu L, Wei J, Zhang Y, Choi H. OP0258 Risk of incident gout associated with initiation of sodium-glucose cotransporter-2 inhibitors versus other second-line agents among metformin users with type 2 diabetes. Ann Rheum Dis. doi:10.1136/annrheumdis-2023-eular.6480

Gout Treatments

The Food and Drug Administration (FDA) has approved Ilaris^® (canakinumab) for the symptomatic treatment of adult patients with gout flares in whom nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.

The approval was based on data from two 12-week, double-blind, active-controlled trials. In the β-RELIEVED study (ClinicalTrials.gov Identifier: NCT01029652) patients were randomly assigned to receive canakinumab 150mg subcutaneously (SC) (n=115) or triamcinolone acetonide 40mg intramuscular (IM) (n=115). In the β-RELIEVED-II study (ClinicalTrials.gov Identifier: NCT01080131) patients were randomly assigned to receive canakinumab 150mg SC (n=112) or triamcinolone acetonide 40mg IM (n=114). Treatment was administered at baseline and thereafter upon a new flare.

Among enrolled patients, 33.5% of the canakinumab group and 36.7% of the triamcinolone group had documented inability to use both NSAIDs and colchicine; the remainder had intolerance, contraindication or lack of response to either treatment. In both studies, the co-primary endpoints were the time to first new gout flare over 12 weeks and patient’s assessment of gout flare pain intensity at the most affected joint at 72 hours postdose (measured on a 0-100mm visual analogue scale).

These endpoints were also evaluated in a third double blind, active-controlled trial (ClinicalTrials.gov Identifier: NCT01356602) that randomly assigned patients to canakinumab 150mg SC (n=132) or triamcinolone acetonide 40mg IM (n=132). Approximately 44% of patients in this study were unable to use NSAIDs and colchicine.

Findings from all 3 studies showed that among patients unable to use NSAIDs and colchicine, pain intensity of the most affected joint at 72 hours postdose was consistently lower for those treated with canakinumab compared with triamcinolone acetonide. Canakinumab treatment was also associated with a reduction in the risk of a new flare when compared with triamcinolone acetonide. The benefits of canakinumab were found to be comparable in the overall study population for both endpoints.

The most common adverse reactions reported with canakinumab were nasopharyngitis, upper respiratory tract infections, urinary tract infections, hypertriglyceridemia, and back pain.

Ilaris is supplied as a 150mg/mL solution in single-dose vials. The recommended dose for adult patients with a gout flare is 150mg SC. For those who require retreatment, there should be an interval of at least 12 weeks before a new dose may be given.

Ilaris, an interleukin-1β blocker, is also indicated for the treatment of periodic fever syndromes and active Still disease.

Treatment with monthly infusions of SEL-212 was found to significantly reduce serum uric acid levels in adults with chronic refractory gout, according to results from two phase 3 trials.

SEL-212 consists of pegadricase, a proprietary pegylated uricase, coadministered with ImmTOR, a nanoparticle technology with rapamycin designed to generate antigen-specific immune tolerance. The double-blind, placebo-controlled DISSOLVE I (ClinicalTrials.gov Identifier: NCT04513366) and DISSOLVE II (ClinicalTrials.gov Identifier: NCT04596540) trials evaluated the efficacy and safety of 2 different dose levels of SEL-212 in adults 19 years of age and older with chronic refractory gout.

Patients were randomly assigned 1:1:1 to receive SEL-212 0.15mg/kg (high dose), 0.1mg/kg (low dose), or placebo via intravenous (IV) infusion every 28 days for a total of up to 12 infusions. The primary endpoint was serum uric acid (sUA) control during month 6, defined as the percentage of patients who achieve and maintain reduction in sUA less than 6mg/dL for at least 80% of the time during month 6.

In DISSOLVE I, 56% and 48% of patients treated with the high dose and low dose of SEL-212, respectively, achieved sUA control during month 6 vs 4% of patients who received placebo (both P <.0001). Treatment with SEL-212 reduced mean serum urate levels overall by 69% compared with placebo (P <.001).

In DISSOLVE II, 47% and 41% of patients treated with the high dose (P =.0002) and low dose (P =.0015) of SEL-212, respectively, achieved sUA control during month 6 vs 12% of patients on placebo.

Among participants 50 years of age and older, treatment with SEL-212 at the high dose resulted in higher response rates for sUA control. In DISSOLVE I, 65% and 47% of patients treated with the high dose and low dose of SEL-212, respectively, met the primary endpoint vs 5% of patients who received placebo (both P <.0001). In DISSOLVE II, 48% and 45% of patients treated with the high dose (P =.0017) and low dose (P =.0044), respectively, met the primary endpoint vs 14% of patients who received placebo.

Commenting on the findings, Herbert S. B. Baraf, MD, FACP, MACR, Clinical Professor of Medicine, George Washington University School of Medicine and Health Sciences and Principal Investigator of the DISSOLVE program, said: “Based on these data, I believe SEL-212 has the potential to provide an important new uricase-based treatment option for patients with chronic refractory gout. The demonstrated profound lowering of the serum uric acid in the DISSOLVE program should meaningfully impact the quality of the lives of these severely afflicted patients.”

Detailed results from both clinical trials will be presented at an upcoming medical meeting. According to Sobi, regulatory submission in the US is expected in the first half of 2024.

Kidney function remains stable over 12 months in most patients with uncontrolled gout treated with a combination of pegloticase and methotrexate, investigators reported at the National Kidney Foundation’s 2023 Spring Clinical Meetings in Austin, Texas.

Methotrexate is used cautiously in patients with mild to moderate chronic kidney disease (CKD) because it is primarily excreted by the kidneys and can contribute to acute kidney injury. The disease-modifying antirheumatic drug is contraindicated in advanced CKD.

Investigators hypothesized that methotrexate would reduce immunogenicity from treatment with pegloticase, a pegylated mammalian recombinant uricase. Results from the original MIRROR randomized controlled trial (Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Krystexxa) showed a higher urate-lowering response rate (71% vs 39%) and lower infusion reaction risk (4% vs 31%) at 6 months among patients randomly assigned to methotrexate (15 mg/week) or placebo, in combination with pegloticase (8mg biweekly infusion). At baseline, patients had a serum uric acid level of 7mg/dL or higher, failure or intolerance to urate-lowering therapy, and 1 or more gout symptoms. Patients with an estimated glomerular filtration rate (eGFR; in mL/min/1.73 m²) less than 40 using the Modification of Diet in Renal Disease equation were excluded.

At 12 months, urate lowering with pegloticase was sustained in 50.0% and 75.8% of the combination treatment group compared with 25.0% and 43.8% of the placebo recipients who had a baseline eGFR of more than 60 and 40-59, respectively, Abdul Abdellatif, MD, of Baylor College of Medicine in Houston, Texas, and colleagues reported.

Over 12 months, mean eGFR increased by 4.6 in the combination treatment group from a baseline value of 69.8 and increased by 1.7 in the placebo group from a baseline level of 69.7. Among patients in the combination group with a baseline eGFR of more than 60 and 40 to 59, CKD stage improved in 14.0% and 44.4%, remained stable in 72.1% and 48.1%, and worsened in 14.0% and 7.4%, respectively, over 12 months.

Dr Abdellatif’s team concluded that “eGFR remained stable in the majority of uncontrolled gout patients treated with pegloticase both in the presence and absence of [methotrexate] co-therapy.” The investigators noted that they observed this effect in patients with stage 3 CKD and an eGFR higher than 40 at baseline. These study findings extend 6 month results presented at an earlier conference.  

Disclosure: This research was supported by Horizon Therapeutics plc. Please see the original reference for a full list of disclosures.

Reference

Abdellatif A, Botson J, Obermeyer K, Padnick-Silver L, Marder B. eGFR changes during pegloticase treatment with and without methotrexate co-therapy: 12-month findings of MIRROR RCT. Presented at: NKF 2023, Austin, Texas, April 11-15. Poster 232.

Intensive urate lowering with pegloticase along with methotrexate cotherapy may improve blood pressure control in patients with uncontrolled gout whether or not they also have chronic kidney disease (CKD). Investigators discussed the latest findings from the MIRROR trial in a poster presentation at the American Society of Nephrology’s Kidney Week 2023 meeting in Philadelphia, Pennsylvania.

In the MIRROR trial, investigators randomly assigned 152 symptomatic patients with a serum uric acid level of 7mg/dL or higher despite urate-lowering therapy to oral methotrexate (15mg/wk) or placebo as cotherapy to pegloticase (8mg biweekly). Inclusion criteria specified 2 or more gout flares in the prior year, gouty arthritis, or tophi. Estimated glomerular filtration rate was required to be above 40 mL/min/1.73 m².

At baseline, systolic blood pressure (133 vs 131 mmHg) and diastolic blood pressure (82 vs 83 mmHg) were comparable in the methotrexate and placebo groups, respectively.

Systolic blood pressured declined more in the methotrexate than placebo co-therapy group by week 24 (-6 vs -1 mmHg) and this reduction was sustained through week 52, Richard J. Johnson, MD, of the University of Colorado in Aurora reported on behalf of his team. Diastolic blood pressure remained 2 mmHg below baseline in the methotrexate group through week 52. Overall blood pressure reduction after week 24 was more pronounced in patients without vs with stage 3 CKD.

In patients treated with placebo plus pegloticase, both systolic and diastolic blood pressure initially declined, then fluctuated thereafter.

“There is increasing evidence that uric acid can promote activation of the renin angiotensin system and cause high blood pressure,” Dr Johnson told Renal & Urology News. “Inflammation in the kidney also causes persistent renal vasoconstriction. These data support a possible role of urate lowering with pegloticase, and a potential anti-inflammatory benefit from methotrexate, in regulating blood pressure, particularly in patients without CKD.”

Patients with tophaceous gout and impaired kidney function might benefit the most from intravenous pegloticase because it is otherwise difficult to treat these patients to a target uric acid level of 6 mg/dL or less by oral treatments alone, he noted. He suggested cotherapy with mycophenolate mofetil instead of methotrexate in patients with an eGFR less than 40 due to positive results from the RECIPE and PROTECT trials.

Disclosure: This research was supported by Horizon Therapeutics. Please see the original reference for a full list of disclosures.

Purified Cortrophin^® Gel (repository corticotropin injection USP) is now available in a 1mL multiple-dose vial (80 USP units/1mL), in addition to the 5mL multiple-dose vial (80 USP units/1mL).

Cortrophin Gel is a purified adrenocorticotropic hormone. In January 2022, ANI Pharmaceuticals reintroduced the product to the market after acquiring the New Drug Application from Merck. In a statement, the Company explained that the new 1-mL vial size “was developed with the goal of helping enable rapid time to therapy, at point-of-care, for appropriate patients with acute gouty arthritis flares.”

In addition to acute gouty arthritis, Cortrophin Gel is indicated in the following disorders:

• Adjunctive therapy for short-term administration in psoriatic arthritis, rheumatoid arthritis (including juvenile rheumatoid arthritis), and ankylosing spondylitis.
• During an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus and systemic dermatomyositis (polymyositis).
• Severe erythema multiforme (Stevens-Johnson syndrome).
• Severe psoriasis.
• Atopic dermatitis.
• Serum sickness.
• Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as allergic conjunctivitis, keratitis, iritis and iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation.
• Symptomatic sarcoidosis.
• Inducing diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or due to lupus erythematosus.
• Acute exacerbations of multiple sclerosis.

“Gout is the most common type of inflammatory arthritis,” said Mary Pao, MD, PhD, Chief Medical Officer of ANI. “Acute gouty arthritis flare patients who are in need of additional flare treatment options, beyond currently recommended first line therapies, have a need for alternatives. The development of the 1-mL vial represents ANI’s commitment to this patient population.”

According to the product labeling, treatment of acute gouty arthritis should be limited to a few days. Additionally, conventional  concomitant therapy should be administered during corticotropin treatment and for several days after it is stopped, as rebound attacks may occur when corticotropin is discontinued.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may reduce the risk for recurrent gout flares and early mortality compared with other diabetes treatments in patients with gout and type 2 diabetes, investigators report.

In an observational study of 5931 patients (mean age, 66 years), initiation of SGLT2i was significantly associated with a 19% lower risk for a first recurrent gout flare and a 21% lower risk for recurrent gout flares overall compared with initiation of glucagonlike peptide-1 receptor agonists (GLP-1 RA) or dipeptidyl peptidase-4 inhibitors (DPP-4i). Compared with GLP-1 RA alone, SGLT2 inhibitors were significantly associated with a 35% lower risk for recurrent flares, Guanghua Lei, MD, PhD, and Chao Zeng, MD, PhD, of Xiangya Hospital, Central South University in Changsha, Hunan, China, and colleagues reported in JAMA Network Open. Use of SGLT2i vs active comparators was associated with 8.1 and 8.8 fewer first and overall recurrent flares, respectively, per 1000 person-years.

SGLT2 inhibitor initiation also was significantly associated with a 29% lower risk for all-cause mortality compared with initiation of GLP-1 RA and DPP-4i, the investigators reported. The SGLT2i group had 6.1 fewer deaths per 1000 person-years than the active comparator group. In subgroup analysis, the lower risk for all-cause mortality among initiators of SGLT21 remained significant only compared with DPP-4i, not GLP-1 RA.

Of the cohort, 11.2% had chronic kidney disease and 7.9% had heart failure. Myocardial infarction and stroke previously occurred in 9.1% and 3.7%, respectively.

In terms of mechanisms, the investigators suggested SGLT2i might increase kidney urate elimination. It may enhance the sirtuin-1 enzyme that inhibits xanthine oxidase,  suppress pyrin domain-containing 3 inflammasome activation, and curb interleukin 1β secretion. SGLT2i use might also improve kidney function and heart failure and reduce the use of loop or thiazides diuretics, and thus indirectly lower the risk for recurrent gout flares.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.