Gout Treatment and Comorbidities

A Retrospective Cohort Study in a Large US Managed Care Population

Paola Primatesta; Estel Plana; Dietrich Rothenbacher

BMC Musculoskelet Disord. 2011;12

Results

Table 1 shows the main characteristics of the 177,637 gout patients included in the study (12 patients were excluded because they had a previous diagnosis of gout within 6 months of the index data). Mean age was 55.2 years (SD 13.1). Men represented the majority of patients (75.6%). Overall, more than half (58.1%) had any of the considered comorbidities; hypertension (36.1%), dyslipidemia (27.0%), diabetes (15.1%) and ischemic heart disease (10.2%) being the most common.

During the 12 months following the index date, 1.2% of patients were hospitalised at least once and 37.0% underwent an outpatient visit. In almost one third of patients (31.8%) the index visit was carried out at the primary care physician office; in only 2.7% it was conducted by a rheumatologist, while it was not known who made the diagnosis in almost 60% of the cases.

Overall 32,244 patients had at least 1 acute gout episode recorded in the database during the follow-up period (mean follow-up (SD) was 2.16 (1.45) years). According to the operational definition of flare used, in the 12 months of follow-up after the first occurrence of a gout claim (starting 30 days after index date) 11% of patients (N = 19,369) had experienced one or more flares.

Table 2 shows the gout related drugs utilization for the whole cohort and separately for men and women in the 12 month of follow-up. Nonselective NSAIDs were the most commonly dispensed (38.7% ever used them: 40.5% of men and 33.3% of women), followed by allopurinol (35.5%), corticosteroids (20.4%) and colchicine (18.3%) in men; and corticosteroids (22.7%), allopurinol (20.6%) and colchicine (11.8%) in women. Notably, 39% of patients (36.9% of men and 45.3% of women) did not receive any prescription medication for gout.

Patients with cardiometabolic comorbidities were significantly more likely to be dispensed selective NSAIDs (7.9% vs 5.5%), colchicine (17.6% vs 15.6%), corticosteroids (22.5% vs 19.1%) and allopurinol (32.6% vs 31.2%) than gout patients with no comorbidites (all p < 0.0001 after adjusting for age). This was true for both genders. Patients with diabetes and cardiovascular comorbidities had similar patterns of anti-gout treatment prescriptions. Compared with those with no comorbidities, patients with renal impairment were less likely to be dispensed nonselective NSAIDs (17.5%), and more likely to receive allopurinol (43.9%), colchicine (27.3%) and corticosteroids (28.3%) (all p-values < 0.0001).

Table 3 shows the gout related drugs dispensed in the 7 days after any flare. During a flare the prescription of NSAIDs and colchicine increased. Almost a third (29.9%) of patients received allopurinol during an acute attack.

Patients with acute attacks were also more likely to receive treatment within 12 months following the index date, compared with the gout population who did not experience flares, as shown in Table 4. In particular, the corresponding numbers dispensed colchicine among patients with no, 1, 2, and 3 or more flares were 12.2%, 49.9%, 66.5% and 80% respectively. 27.9% of patients with no flares received allopurinol during the 12 months of follow-up, vs. 60.8%, 77.8% and 87.8% of patients with 1, 2, and 3 or more flares respectively. Patients with 3 or more flares were also more likely to be dispensed corticosteroids (70.6%) than those with 1 flare (45.7%) (Table 4).

Table 5 shows the results of the multivariable analysis. The risk of flares was associated with older age in women (highest at age 60–69), while in men it decreased by age. It was also positively associated with cardiometabolic comorbidities. Women with these conditions were 60% more likely to have flares (incidence rate ratio, IRR 1.60;1.48–1.74), while men were 10% more likely (IRR 1.10; 1.06–1.13). Gastrointestinal diseases were negatively associated with flares in women (IRR 0.86; 0.78–0.96) while a positive association was seen in men (IRR 1.07; 1.02–1.13). (Table 5).

When use of diuretics was entered in the model it showed a positive association with flares both in women (IRR 4.34; 4.03–4.68) and in men (IRR 1.9 1; 1.50–1.98) (data not shown).

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Table 1. Demographic characteristics of gout patients (N = 177,637)
	N	%
Male gender	134,333	75.6%
Age in categories
20–49	59,371	33.4%
50–59	54,612	30.7%
60–69	37,016	20.8%
70–79	19,790	11.1%
80–89	6,848	3.9%
Comorbidities:
Cardiometabolic	91,203	51.3%
Congestive Heart Failure	7,467	4.2%
Ischemic Heart Disease	18,066	10.2%
Hypertension	64,094	36.1%
Conduction and rhythm disorder	12,034	6.8%
Cerebrovascular disease	4,934	2.8%
Peripheral arterial disease	6,271	3.5%
Chronic renal impairment	5,718	3.2%
Dyslipidemia	47,960	27.0%
Diabetes	26,818	15.1%
Gastrointestinal	14,224	8.0%
Gastrointestinal	11,836	6.7%
Hepatic disorders	2,718	1.5%
Pancreatic disorders	501	0.3%
Haematological (Anemia)	3,829	2.2%
Myopathy	159	0.1%
Arthritis	25,516	14.4%
Osteoporosis	5,044	2.8%
Any comorbidity	103,281	58.1%
Gout diagnosis recorded by:
Primary care physician	56,512	31.8%
Rheumatologist	4,731	2.7%
Emergency visit	10,482	5.9%
Other or Unknown specialty	105,912	59.6%
Hospitalized in 12 months follow-up (at least once)	2,119	1.2%
Outpatient visit in 12 months follow-up (at least once)	65,665	37.0%
Number of flares in 12 months follow-up:
0	158,268	89.1%
1	15,893	9.0%
2	2,790	1.6%
3 or more	686	0.4%

Table 2. Gout related treatment patterns overall and by presence of comorbidities
Gout-related medication	Ever use during 1 year after gout diagnosis
ALL	All		No comorbidities (n = 74,356)		Cardiometabolic§ (n = 64,385)			Diabetes (n = 26,818)		Chronic renal impairment (n = 5,718)
ALL	n	%	n	%	n	%	p-value*	n	%	n	%
NSAIDS	74,055	41.7%	32,701	44.0%	25,994	40.4%	0.022	9,592	35.8%	1,134	19.8%
selective	12,455	7.0%	4,102	5.5%	5,077	7.9%	< .0001	1,942	7.2%	219	3.8%
nonselective	68,826	38.7%	31,167	41.9%	23,765	36.9%	0.173	8,660	32.3%	1,001	17.5%
Colchicine	29,686	16.7%	11,595	15.6%	11,327	17.6%	< .0001	4,950	18.5%	1,559	27.3%
Corticosteroids	37,224	21.0%	14,182	19.1%	14,476	22.5%	< .0001	5,153	19.2%	1,617	28.3%
Probenecid	2,510	1.4%	1,108	1.5%	901	1.4%	0.249	331	1.2%	58	1.0%
Allopurinol	56,544	31.8%	23,215	31.2%	20,971	32.6%	< .0001	9,183	34.2%	2,512	43.9%
*No treatment*	*69,241*	*39.0%*	*29,202*	*39.3%*	*24,938*	*38.7%*	*< .0001*	*10,669*	*39.8%*	*2,171*	*38.0%*
FEMALES	N = 43,304		N = 12,387		N = 17,418			N = 9,381		N = 2,025
NSAIDS	16,183	37.4%	4,641	37.5%	6,464	37.1%	< .0001	3,279	35.0%	368	18.2%
selective	3,815	8.8%	911	7.4%	1,643	9.4%	< .0001	769	8.2%	77	3.8%
nonselective	14,423	33.3%	4,255	34.4%	5,684	32.6%	0.000	2,899	30.9%	320	15.8%
Colchicine	5,096	11.8%	890	7.2%	2,312	13.3%	< .0001	1,558	16.6%	483	23.9%
Corticosteroids	9,831	22.7%	2,438	19.7%	4,213	24.2%	< .0001	1,954	20.8%	575	28.4%
Probenecid	441	1.0%	96	0.8%	195	1.1%	0.359	115	1.2%	27	1.3%
Allopurinol	8,905	20.6%	1,676	13.5%	4,006	23.0%	< .0001	2,692	28.7%	834	41.2%
No treatment	19,637	45.3%	6,200	50.1%	7,693	44.2%	< .0001	3,991	42.5%	816	40.3%
MALES	N = 134,333		N = 61,969		N = 46,967			N = 17,437		N = 3,693
NSAIDS	57,872	43.1%	28,060	45.3%	19,530	41.6%	0.575	6,313	36.2%	766	20.7%
selective	8,640	6.4%	3,191	5.1%	3,434	7.3%	< .0001	1,173	6.7%	142	3.8%
nonselective	54,403	40.5%	26,912	43.4%	18,081	38.5%	0.012	5,761	33.0%	681	18.4%
Colchicine	24,590	18.3%	10,705	17.3%	9,015	19.2%	< .0001	3,392	19.5%	1,076	29.1%
Corticosteroids	27,393	20.4%	11,744	19.0%	10,263	21.9%	< .0001	3,199	18.3%	1,042	28.2%
Probenecid	2,069	1.5%	1,012	1.6%	706	1.5%	0.260	216	1.2%	31	0.8%
Allopurinol	47,639	35.5%	21,539	34.8%	16,965	36.1%	< .0001	6,491	37.2%	1,678	45.4%
No treatment	49,604	36.9%	23,002	37.1%	17,245	36.7%	< .0001	6,678	38.3%	1,355	36.7%

§ Cardiometabolic disease include congestive heart failure, ischaemic heart disease, hypertension, cerebrovascular disease, peripheral arterial disease, dyslipidemia.
* P-value from logistic model with drug as outcome associated to cardiometabolic comorbidities vs no comorbidities adjusting for age in categories (20–49, 50–59, 60–69, 70–79, 80–89).

Table 3. Treatment patterns for treatment of flares occurring at any time during the study period
Gout drugs within 7 days of flare
	(any flare) n = 32,244
	n	%
NSAIDS	21,633	67.1%
selective	1,283	4.0%
nonselective	20,748	64.3%
Colchicine	12,847	39.8%
Corticosteroids	8,598	26.7%
Probenecid	420	1.3%
Allopurinol	9,644	29.9%
No treatment	0	0.0%

Table 4. Treatment patterns: patients with no flares and with flares occurring during follow-up of 12 months (N = 19,369)
Ever during 12 months after index date	No flares		Total (any flare)		1 flare		2 flares		3 flares
Ever during 12 months after index date	No flares			(n = 19,369)		(n = 15,893)		(n = 2,790)		(n = 686)
	n	%	n	%	n	%	n	%	n	%
NSAIDS	58325	36.9%	15730	81.2%	12821	80.7%	2338	83.8%	571	83.2%
selective	10110	6.4%	2345	12.1%	1795	11.3%	430	15.4%	120	17.5%
nonselective	53750	34.0%	15076	77.8%	12278	77.3%	2245	80.5%	553	80.6%
Colchicine	19353	12.2%	10333	53.3%	7929	49.9%	1855	66.5%	549	80.0%
Corticosteroids	28379	17.9%	8845	45.7%	6695	42.1%	1666	59.7%	484	70.6%
Probenecid	1781	1.1%	729	3.8%	503	3.2%	174	6.2%	52	7.6%
Allopurinol	44110	27.9%	12434	64.2%	9662	60.8%	2170	77.8%	602	87.8%
No treatment	69241	43.7%	0	0.0%	0	0.0%	0	0.0%	0	0.0%

Table 5. Poisson multivariate regression model for number of flares during follow-up of 12 months by sex
		Females (N = 43,304)			Males (N = 134,333)
		IRR	95% CI	p-value	IRR	95% CI	p-value
Age	< 50	1.00	(ref.)		1.00	(ref.)
	50 - 59	1.66	(1.49, 1.85)	< .0001	0.83	(0.80, 0.85)	< .0001
	60 - 69	1.93	(1.73, 2.16)	< .0001	0.76	(0.73, 0.79)	< .0001
	70 - 79	1.69	(1.51, 1.90)	< .0001	0.56	(0.53, 0.60)	< .0001
	80 - 89	1.31	(1.12, 1.52)	0.001	0.53	(0.48, 0.59)	< .0001
Comorbidities:
Cardiometabolic*		1.60	(1.48, 1.74)	< .0001	1.10	(1.06, 1.13)	< .0001
Diabetes		1.48	(1.35, 1.63)	< .0001	0.97	(0.93, 1.02)	0.262
Gastrointestinal		0.86	(0.78, 0.96)	0.005	1.07	(1.02, 1.13)	0.011
Hematological		1.03	(0.88, 1.20)	0.720	0.94	(0.84, 1.06)	0.340
Myopathy		1.21	(0.50, 2.91)	0.670	0.84	(0.50, 1.42)	0.509
Osteoporosis		0.88	(0.78, 1.00)	0.044	1.11	(0.99, 1.25)	0.076

IRR = Incidence rate ratio.
* Cardiometabolic disease include congestive heart failure, ischaemic heart disease, hypertension, cerebrovascular disease, peripheral arterial disease, dyslipidemia.

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