Patient Characteristics

A total of 12 patients were interviewed. All demographic and clinical sampling quotas implemented to promote heterogeneity and representation of the Sjögren’s population (Table 2) were met or exceeded except for the education level category ‘completed high school or below only’ (≥ 3 target; 2 actual). Patients were mostly female (n = 8/12; 67%) with a mean age of 56.1 years (range 20–80 years). Although Sjögren’s is more common in white individuals (hence the racial quota relating to white and non-white) [43], white and non-white individuals were equally represented (n = 6/12; 50%, each) (Table 2). Most patients (n = 10/12; 83%) had received a Sjögren’s diagnosis within the last 10 years and were predominately classified as having moderate (n = 5/12; 42%) or high (n = 4/12; 33%) disease activity on the basis of PhGA score. At screening, most patients (n = 9/12; 75%) had an unsatisfactory symptom state (≥ 5 ESSPRI score) and experiences of eye dryness (n = 12/12; 100%), tiredness/fatigue (n = 11/12; 92%) and mouth dryness (n = 8/12; 67%), among other symptoms.

Table 2 Demographic and clinical characteristics as reported by patients at screening (N = 12)Physician Characteristics

A total of ten physicians, all rheumatologists, were interviewed and met all sampling quotas. Five (n = 5/10; 50%) physicians were female, and were predominantly from the USA (n = 8/10; 80%). All physicians had been qualified for at least 10 years, treating patients for at least 5 years and treating patients with Sjögren’s on a weekly (n = 9/10; 90%) or monthly (n = 1/10; 10%) basis at the time of interview. On average, physicians treated at least 20 patients with Sjögren’s per month and worked in a range of settings, including academia (n = 8/10; 80%), private practice (n = 3/10; 30%) and/or hospital-based care (n = 2/10; 20%). Physicians reported using ESSDAI (n = 7/10; 70%) and ESSPRI (n = 4/9; 44%) to assess Sjögren’s disease activity in their clinical practice.

ESSDAIAppropriateness of Domain Weights

Most domain weights were considered clinically appropriate by most (≥ 50%) physicians (Fig. 2). However, the glandular (domain weight of 2), articular [2] and biological [1] domains were considered slightly underweighted and the muscular [6] domain was considered slightly overweighted by ≥ 50% of physicians. Physicians who considered the glandular (n = 5/10; 50%), articular (n = 6/10; 60%) and/or biological (n = 6/10; 60%) domains slightly underweighted commented on the domains representing an important/prevalent aspect of disease activity, being significantly impactful to patients’ feelings and functioning, and/or being relevant to assess in the context of a clinical trial. However, physicians suggested that these domain weights were only ‘a little low’, and recommendations for increased weights tended to only be 1–2 points higher. Physicians who suggested that the muscular domain was slightly overweighted (n = 7/10; 70%) stated that muscular involvement due to Sjögren’s is rare and/or not as severe as other organ involvement. Additionally, physicians reported that it can be difficult to separate muscular involvement due to Sjögren’s from other comorbid conditions and weakness due to steroids. Again, the weight was only considered ‘a little high’, and despite these suggestions of increasing/decreasing domain weights, no physicians suggested that ESSDAI was inappropriate for use in its current format.

Fig. 2

Appropriateness of ESSDAI domain weights

Meaningful Improvement

All physicians asked reported that a one-category improvement (e.g. moderate to low activity level) would be clinically meaningful for the constitutional (n = 10/10; 100%), pulmonary (n = 10/10; 100%), renal (n = 8/8; 100%) and biological domains (n = 8/8; 100%). For the remaining domains, a minority of physicians reported that a two-category improvement (e.g. moderate to no activity level) would be clinically meaningful (≤ 30%). Reasons for a two-category improvement included the domain typically being responsive to treatment (glandular, articular, cutaneous, muscular), there being natural fluctuation in the domain (glandular, articular), variation/subjectivity in how the disease activity levels are interpreted by physicians (cutaneous, PNS), and requiring a change substantial enough to make the patient feel better (CNS, haematological). For seven domains, all or most physicians (≥ 80%) reported that patients would also consider the same level of improvement meaningful (one or two categories). For the L&L, muscular and haematological domains, a few physicians (≤ 30%) reported that the change may not be meaningful to patients, and some physicians (≤ 40%) reported that patients were unlikely to notice changes in the renal and biological domains, as these changes would be more evident in objective tests of disease activity (e.g. complement and Immunoglobulin G (IGG) levels) as opposed to patients’ feeling and functioning.

The existing MCII threshold of 3 points on the ESSDAI total score [16, 19] was most frequently reported as clinically meaningful by physicians (n = 5/10; 50%). However, notable caveats included meaningfulness being dependent upon the domains that have changed (n = 1/2; 50%), and patients’ baseline ESSDAI score (n = 1/2; 50%).

Best Approach to Calculating an ESSDAI Score

Owing to interview time constraints, only four physicians (n = 4/10; 40%) discussed the best approaches to calculating and tracking ESSDAI total scores. Four approaches were recommended: the validated approach of summing weighted domain scores to calculate a total score (n = 2/4; 50%) [10, 19, 21], tracking individual domain scores (n = 2/4; 50%), calculating separate total scores for domains in which disease activity is reversible versus irreversible (n = 1/4; 25%), and generating a total score without domain weights (n = 1/4; 25%). The two physicians (n = 2/4; 50%) who recommended tracking individual domain scores did so to avoid changes within domains being diluted within a total score (n = 1/2; 50%) and to separately track domains in which disease activity is reversible or irreversible (n = 1/2; 50%). To note, this was a misconception, domains should not be scored when damage is present. The physician that suggested calculating an ESSDAI score without domain weights only did so to reduce the complexity of the calculation (n = 1/4; 25%).

ESSPRIRelevance and Interpretation of ESSPRI Items

ESSPRI items were considered relevant to most patients within the 2-week recall period: dryness (n = 12/12; 100%), fatigue (n = 10/12; 83%) and pain (n = 11/12; 92%). However, there was variation in interpretation of the dryness item, with most patients considering more than one area [eye dryness (n = 9/11; 82%), mouth dryness (n = 4/11; 36%) and skin dryness (n = 3/11; 27%)] and tending to focus on the most severe areas of dryness.

Recall Period

The 2-week recall period was considered appropriate to assess average symptom severity by most physicians (n = 7/10; 70%). Reasons for this included the recall period accounting for day-to-day variability of symptoms (n = 2/7; 23%) and patients with Sjögren’s being ‘focused’ on their symptoms allowing for reliable self-reports (n = 2/7; 23%). However, two physicians (n = 2/10; 20%) suggested that patients may think only about their worst symptoms, and one physician (n = 1/10; 10%) felt the recall period is too long relative to shorter recall periods used in other rheumatologic diseases and may diminish treatment efficacy. A subset of physicians (n = 5/6; 83%) considered the 2-week recall period to be clinically meaningful. Only one physician provided a rationale, explaining that, as Sjögren’s symptoms fluctuate day to day, having a general trend is more clinically meaningful when considering treatment choices.

Almost all patients (n = 11/12; 92%) reported that it would be easy to remember symptom severity over the past 2 weeks. Most patients demonstrated an understanding of the 2-week recall period (≥ 92%) and considered the recall period appropriate (≥ 83%) across individual items.

Meaningful Change

Most patients reported that a 2-point (n = 5/12; 42%) or 1-point (n = 3/12; 25%) (range 1–6) improvement in their total ESSPRI score would be meaningful, and that a 2-point improvement (n = 5/11; 45%) would justify using a new treatment (range 1–4). Patients reported that a 1-to-2-point improvement would reduce symptom severity (n = 1/5; 20%), frequency (n = 1/5; 20%) and bothersomeness (n = 1/5; 20%), reduce impact to activities of daily living (n = 1/5; 20%) and improve emotional wellbeing (n = 1/5; 20%). Similarly, most patients felt a 1-point (n = 4/12; 33%) or 2-point (n = 6/12; 50%) worsening in their total ESSPRI score would be meaningful. Table 3 provides patient quotes reflecting how ESSPRI total score improvements would affect how they feel and function.

Table 3 Impact of improvement in ESSPRI total score on how patients feel/functionPhGA

Both PhGA items were well understood by physicians, the majority (≥ 80%) considering both systemic and glandular disease activity when responding to both items. However, the Likert version was interpreted more consistently as referring specifically to disease activity than the 0–10 NRS version, for which physicians reported that they would consider a range of concepts in addition to disease activity, including symptoms (n = 9/10; 90%), impacts (n = 4/10; 40%) and global health status (n = 3/10; 30%). Physicians frequently reported that they would require objective laboratory test results (e.g. blood work, inflammatory markers or complement antibodies levels; ≥ 71%), conduct physical examinations (≥ 56%) and/or collect patient-reported information (≥ 43%) before answering each version.

PaGA

Although both PaGA items were well understood, the Likert version was interpreted more consistently as an assessment of overall symptom severity with most patients considering all their symptoms when responding (n = 11/12; 92%). The 0–10 NRS version varied in interpretation, with fewer patients considering all their symptoms (n = 5/12; 42%) and some considering the effects/impacts of Sjögren’s (n = 2/12; 17%) and/or specific symptoms only [eye dryness (n = 4/12; 33%), mouth dryness (n = 1/12; 8%) and pain (n = 1/12; 8%)]. Patient and physician preferences for different response scales, including the 0–10 NRS and Likert scale used in the PaGA/PhGA items, were also explored during interviews, and the findings are published elsewhere [44].