Targeted Literature Review

The search strategy yielded 135 abstracts; based on the inclusion and exclusion criteria 41 were selected for in-depth review (Fig. 1).

Fig. 1

Targeted literature review. aExclusion criteria for key symptoms and impacts of gout: abstract is about a different type of gout and does not discuss gout generally; discusses gout as it related to a pediatric population; and research search term(s) are included in the title and/or abstract but are not the main focus of article. Exclusion criteria to identify and review studies that report on the psychometric performance/meaningful change of existing clinical outcome assessments employed in the current phase 3 trial: abstract does not discuss validation of SF-36 or HAQ-DI in gout; does not discuss SF-36 or HAQ-DI meaningful change scores in relation to gout; or is related to a pediatric population. HAQ-DI Health Assessment Questionnaire-Disability Index; SF-36 36-Item Short Form Survey

Participant Demographics and Health Status

Table 1 presents demographic data and participant-reported health information. The mean age was 55.9 years (standard deviation [SD] = 12.1 years), a majority of whom self-identified as male (n = 14, 70.0%) and non-Hispanic white (n = 11, 55.0%). Twelve participants (60.0%) reported severe gout flares (defined as more than three flares in ≤ 6 months) and tophi severity was reported as severe (more than three tophi in ≤ 6 months) by seven participants (35.0%).

Table 1 Participant-reported demographic information and health informationSymptoms

Signs and symptoms reported by the participants are presented in Fig. 2a and Supplemental Table 1. Bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%) were most frequently reported. When describing bodily pain, participants remarked how pain repeatedly impeded their mobility and ability to do certain things, such as get out of bed and walk.

Fig. 2

a Signs and symptoms reported by participants with their b mean bothersome ratings c order of most important to treat and d meaningful change ratings (N = 20). a Participant-reported signs and symptoms. b Mean bothersome rating of signs and symptoms. c Most important sign or symptom to treata. aParticipants were able to provide multiple answers to the question: “Of all the symptoms that you experience [list signs/symptoms] which are the most important to treat? Why?”. d Meaningful change ratingb. bNot all participants provided meaningful change data for each symptom they reported; this was due to either comprehension issues or interview time constraints

Joint pain and joint tenderness were the most bothersome symptoms (Fig. 2b and Supplemental Table 1). One participant likened their joint pain to “someone putting a knife through your joint when you’re taking a step”, while another reported that it felt like they are “walking on nails and glass”. Four participants (20.0%) noted that joint tenderness prevented them from falling asleep “as even a bedsheet could cause pain”.

Most important to treat Participants were asked which signs/symptoms they felt were the most important to treat and eight (40.0%) responded with more than one sign or symptom. Bodily pain was most frequently reported as important to treat (n = 14, 70.0%) (Fig. 2c). One participant reported that one symptom often caused another: “… the tophi thing is probably the cause of everything, though, I would guess. I mean, because if you didn’t have that, then this wouldn’t be happening…”.

Meaningful changes in signs or symptoms of chronic refractory gout Participants were asked what improvement in each sign/symptom would be considered to be meaningful (defined to participants during interviews as “…an improvement in your health where you feel better, but it does not necessarily mean that your [symptom] is completely cured”) (Fig. 2d and Supplemental Table 1). Participant quotes included “the pain and the discomfort (associated with joint swelling) would need to improve” and “I think it would have to at least alleviate joint pain from being a daily thing. You know what I mean? If it was maybe once or twice a week, I think it could possibly be more tolerable”.

Impacts of Chronic Refractory Gout

Figures 3a, b, and Supplemental Table 2 present the impacts of chronic refractory gout and related bothersome ratings. Due to interview time constraints, bothersome ratings were not collected for emotional impacts, use of aids and devices, activities that participants required assistance from others, and work-related impacts.

Fig. 3

Participant-reported a impacts with their b mean bothersome ratings and c meaningful change ratings. a Participant-reported impacts (N = 20). aThe majority of participants (n = 14, 70.0%) were asked directly about climbing a flight of stairs. Some participants (n = 6, 30.0%) were not asked about climbing a flight of stairs, because it was determined they would be affected given they reported having difficulty climbing five steps. bThe majority of participants (n = 13, 65.0%) were asked directly about climbing several flights of stairs. Some participants (n = 7, 35.0%) were not asked about climbing several flights of stairs, because it was determined they would be affected given they reported difficulty climbing five steps. b Mean bothersome ratings of impacts. c Meaningful change rating (N = 20)c. cSome participants endorsed more than one way in which a meaningful change could occur

Difficulty completing chores (n = 19, 95.0%) and running errands and shopping (n = 19, 95.0%) were the most frequently reported impacts to daily activities (Fig. 3a and Supplemental Table 2). Participants also reported difficulties with eating and drinking activities, such as gripping and twisting objects (n = 12, 60.0%) and opening previously opened jars (n = 12, 60.0%). Exemplifying the difficulty completing chores, a participant noted that “when I wash dishes, that hurts to stand there on it”.

All participants reported an impact on their ability to climb a flight of stairs (100.0%) and several flights of stairs (100.0%; Fig. 3a and Supplemental Table 2). The average bothersome rating was 8.6 (Fig. 3b and Supplemental Table 2). One participant with difficulty climbing a flight of stairs reported that “… it seems like you’ll end up crawling upstairs. And then not put any pressure on your foot, you are pretty much on your hands and knees going upstairs”.

When asked about activities related to bathing and bathroom use, the ability to shower/wash/dry (n = 16, 80.0%) was the most frequently reported impact (Fig. 3a and Supplemental Table 2). One participant noted, “…when I have a gout flare-up, it affects me getting into the shower. As far as like pivoting and moving my feet to get stable to get into the shower, that affects me”.

When describing their use of aids and devices for support, participants most commonly reported using canes (n = 12, 60.0%; Fig. 4). When detailing their support needs from others, participants most often reported needing assistance with errands and chores (n = 15, 75.0%; Fig. 4). Emotional impacts, which were reported by 19 participants (95.0%), included feeling worn out (n = 16, 80%). Participants also reported impact on their sex life (n = 8, 40.0%) and their ability to work (n = 17, 85.0%; Fig. 4). More than half of the participants (n = 12, 60.0%) reported work impacts related to symptoms of their chronic refractory gout; however, some (n = 3, 15.0%) reported that these impacts were due to emotional hardship, such as feeling sad or anxious. Eighteen participants (90.0%) reported impact on sleep because of chronic refractory gout (Fig. 3a and Supplemental Table 2).

Fig. 4

Impacts of chronic refractory gout: impacts on work and professional life, activities requiring assistance from others, and use of aids and devices

Meaningful changes in impacts of chronic refractory gout Fig. 3c and Supplemental Table 2 present participants’ responses when asked what would need to improve with each impact in order to consider the change or improvement to be meaningful (e.g., improvements in frequency, bothersomeness, and/or difficulty in doing the activity). Participant quotes included “I would say that while I’m walking and stuff, it just—it is not a normal gait” and “You don’t want to be around nobody [sic]. And you don’t want nobody [sic] around you when you have gout. You want to separate yourself”.

Data Saturation

Conceptual saturation for all spontaneously reported signs/symptoms and impacts are summarized and presented in Fig. 5. Conceptual saturation was assessed for the 12 unique signs/symptoms and 24 impacts spontaneously reported by participants. No new signs/symptoms were introduced in the last five (25.0%) interviews; three new impacts were introduced, which were sex life, bending, and ability to get in/out of car. It should be noted that the new concepts were all probed separately in the interviews.

Fig. 5

Saturation graph for the signs/symptoms and impacts of chronic refractory gout (N = 20)

Conceptual Mapping of the HAQ-DI to Concept Elicitation Data

Figure 6 shows that all 20 items of HAQ-DI [28, 29] mapped to impacts reported by participants during interviews, and each were endorsed by at least five (25.0%) participants. Most highly endorsed domains included arising and walking; and most highly endorsed concepts were the ability to climb up five steps, walk outdoors on flat ground, run errands and shop, and do chores such as vacuuming or yard work (n = 19, 95.0% for all).

Fig. 6

Concept mapping HAQ-DI [28, 29] to concept elicitation data. a‘Bathing/hygiene’ was not included in the preliminary hypothesized conceptual model but was frequently reported during interviews. b‘Arising’ was not included in the preliminary hypothesized conceptual model; however, difficulty arising (e.g., getting in and out of bed, standing up from a chair) was reported by the majority of participants as an impact of chronic refractory gout. c‘Feeding oneself’ was not included in the preliminary hypothesized conceptual model, but was frequently reported during interviews. HAQ-DI Health Assessment Questionnaire-Disability Index

The least commonly endorsed domains were eating and grip; however, all items within both were endorsed at higher rates by participants who reported hand, elbow, and/or wrist tophi compared with participants who only experienced chronic refractory gout in their feet, ankles, or knees. One participant remarked, “It affects it a whole bunch. Like I said, you don’t want to move your fingers, you don’t want to bend them at all. [Regarding jars and bottles], even if it’s already open, you just take the lid off, it’s hard”.

Conceptual Mapping of the SF-36 to Concept Elicitation Data

Figure 7 shows all the concept elicitation data mapped to items of the SF-36 [27]; all concepts assessed in the concept elicitation interviews were endorsed by at least five participants (25.0%) and 55% or more for the majority. Participants most frequently endorsed lifting or carrying groceries, walking more than a mile, and walking several hundred yards (n = 18, 90.0% for all). Nineteen participants (95.0%) endorsed at least one negative emotional impact.

Fig. 7

Concept mapping SF-36 [27] to concept elicitation data. aItem 4a and 5a use identical language. bItem 4b and 5b use identical language. SF-36 36-Item Short Form Survey

Conceptual Model

Results of the qualitative interviews were used to further refine the conceptual model (Fig. 8); six additional symptoms were added. Nine participants (45.0%) reported experiencing muscle weakness due to their chronic refractory gout. Itching, cramps, difficulty breathing, kidney stones, and loss of finger movement were each spontaneously reported by one participant (5.0%).

Fig. 8

Reproduced from POS0528 Patient Experiences With Chronic Refractory Gout and its Impact On Health-Related Quality Of Life, Annals of the Rheumatic Diseases, Oladapo A, Strand V, Kragh N, Johnson N, Yousefian C, Brooks D, Sharp H, Kim C, Pillinger M, 82, 527–528, 2023 with permission from BMJ Publishing Group Ltd

Conceptual model for symptoms and impacts of chronic refractory gout. Bolded indicates reported by at least 50.0% of participants in interviews; Italics indicates identified in the literature review.