Study | Type of Study | Type of Flare Use: Design/inclusion/outcome | Flare Definition | Category of Flare Definition | Participant Criteria |
---|---|---|---|---|---|
Marty, et al2 | Development and assessment of a diagnostic method | Outcome | Score ≥ 7 determined by presence of morning stiffness longer than 20 min (score = 1), nocturnal awakenings (= 2), effusion (= 2), limp (= 3), swelling (= 3), warmth (= 3; total = 14) | Quantitative | Referred by general practitioner and rheumatologist. Met clinical and radiological criteria for knee OA according to ACR criteria. Either had stable disease or were experiencing a flare-up according to the physician’s assessment. |
Murphy, et al5 | Development and assessment of a diagnostic method | Outcome | INDIVIDUAL definition of “what pain flare means to you;” during the 7-day period; defined in terms of pain quality (e.g., sharp, increase in pain, intense), timing (e.g., sudden onset, short duration, or variable), and antecedents and consequences (specific activities, e.g., stairs, walking, sitting too long; resort to medication). INVESTIGATOR definition: inadequate pain relief for an episode of intense pain that is usually brought on by too much activity | Qualitative | Community-living adults > 50 yrs of age recruited from pain clinic; knee OA (ACR criteria) |
Esen, et al6 | Development and assessment of a diagnostic method | Outcome | Pain on a single knee for last 72 h with VAS > 30 mm; also uses WOMAC, but no definition of what level of pain, etc. constitutes flare | Quantitative | Pain on a single knee (for the last 72 h VAS > 30 mm); ACR criteria; ≥ 40 yrs of age; KL grade ≥ 2 |
Wise, et al7 | Longitudinal, observational cohort | Inclusion/outcome | Interview: subject reported WOMAC score in the highest 30% of all WOMAC scores: yes or no | Qualitative | Age ≥ 50 years; males and females; physician-diagnosed hip and/or knee OA; pain in hip or knee on at least 15 out of the last 30 days at baseline; had at least 1 case period (flare) and at least 1 control period |
Chapple, et al8 | Observational/review | Outcome | Progression of disease: deterioration in functional status or pain on WOMAC or VAS, or radiographic change as increase in KL grade or joint space narrowing score, increase in osteophytes, or decrease in joint space width | Quantitative | Adults aged over 18 years; males and females; any duration of symptoms; knee OA classified by clinical or radiographic reference standards |
Makovey, et al9, Zobel, et al10, Ferriera, et al11 | Observational | Outcome | Disabling increase in knee symptoms lasting longer than 8 h without settling. Increase in knee pain severity of 2 points from baseline on a NRS (0–10) | Quantitative | Aged ≥ 40 years; have active e-mail address and access to Internet; experience pain that fluctuates in intensity in at least 1 knee on most days in the past month; radiographic evidence of knee OA |
Weaver, et al12 | Subcategory of RCT | Inclusion | Pain, PtGA, and PGA. Defined as worsening of knee pain on motion or knee pain on weight-bearing and worsening of both the patient’s and PGA to at least a score of 2, with a ≥ 1 grade worsening from screening | Quantitative | Adults, > 100 lbs with history of OA knee for at least 6 mos and radiographic evidence of OA |
Zhao, et al13 | Clinical trial | Design | Worsening of signs and symptoms of the disease after discontinuation of NSAID or other analgesics for 2- to 7-day washout period. Uncertain how measured | Quantitative | Men and women outpatients; ≥ 18 yrs; symptomatic OA; met ACR criteria for primary OA knee ≥ 3 mos, functional class I, II or III |
Yocum, et al14 | Clinical trial | Design | Worsening of disease activity from initial screening that included at least 1 grade deterioration in PGA of disease, increase of at least 100 mm on VAS for PtGA of disease activity, increase greater than 35 mm on patient overall assessment of pain | Quantitative | Current NSAID user; ≥ 40 yrs of age; at least 3-mos history of OA knee confirmed radiographically and by signs and symptoms; pain on movement in target joint; experienced flare after ceasing NSAID for 3 days from baseline visit |
Theiler, et al15 | Clinical trial | Design | No definition of flare | — | Males and females ≥ 50 yrs, painful OA of the knee or hip according to ACR criteria; intake of NSAID for at least 5 days prior to study entry; pain intensity of 40 mm or more on the VAS in the previous 48 h when walking on a flat surface; be reluctant to continue on previous NSAID and be willing to change drug treatment; at least grade II to IV on the KL scale on a radiograph taken within the previous 12 mos |
Cibere, et al16 | Clinical trial | Design | Either the patient’s perception of worsening of symptoms with a concomitant increase by at least 20 mm in WOMAC pain on walking (clinically important change), or a significant worsening in the PGA by at least 1 grade (1–5 scale) | Quantitative | (1) OA knee, met ACR criteria, (2) KL grade ≥ 2; (3) current daily use of glucosamine for at least 1 mo, (4) at least moderate improvement in knee pain since starting on glucosamine, measured on a 6-point scale of knee pain |
Baer, et al17 | Clinical trial | Design | Between screening visit (when therapy withdrawn) and baseline: an increase in total WOMAC pain subscale score of at least 2 and at least 25%, with a baseline total WOMAC pain score of at least 6 (out of a possible 20), and a score of ≥ 2 (out of a possible 4) on at least 1 of the 5 items in the WOMAC pain subscale | Quantitative | Men and women, age 40–85 yrs, radiologically confirmed primary OA knee and a flare of pain at baseline following discontinuation of prior therapy |
Rother, et al18 | Clinical trial | Design | (1) Pain in the index knee on walking > 40 mm on VAS, (2) increased by > 15 mm compared with pain on prestudy treatment (screening), and (3) PtGA score for OA of 3–5 and at least 1 grade increase from screening | Quantitative | Minimum 6-mos history of knee OA; met 2 of the following: (1) morning stiffness ≥ 30-min, crepitus on motion and age > 40 yrs; (2) rate knee pain > 3 on a 5-point Likert scale; and (3) taking oral NSAID at least 3 days/week for the past 3 mos or for 25 of the past 30 days |
Boswell, et al19 | Clinical trial | Design | A worsening in WOMAC pain Q1 from screening of ≥ 15 mm, and have ≥ 1 point worsening between screening and baseline for the PtGA of arthritis condition | Quantitative | Men and women ≥ 40 yrs of age; symptomatic primary knee OA ≥ 3 mos; met ACR criteria for OA knee; recent (≤ 12 mos) radiographic evidence of tibiofemoral OA (grade 2 or 3 on the KL scale); ARA functional class rating of I, II, or III |
Hochberg, et al20 | Clinical trial | Design | WOMAC pain score of ≥ 40 mm at baseline, mean change in WOMAC pain score from screening to baseline of ≥ 15 mm, worsening of PtGA by ≥ 1 point | Quantitative | ≥ 50 years of age, 6-mos history of symptomatic, clinically diagnosed OA knee (meeting ACR criteria); ACR functional class rating of I, II, or III, receiving a stable dose of NSAID, COX-2–selective inhibitors, or other oral analgesic therapy for 6 weeks. Agreed to maintain physical activity at a stable level throughout the study |
Essex, et al21 | Clinical trial | Design | A flare was demonstrated if the physician’s and PtGA of arthritis were both “fair,” “poor,” or “very poor” at the baseline visit, and if the baseline patient’s assessment of arthritis pain VAS measurement was between 40–90 mm (on 100 mm scale; 0 = no pain and 100 = very severe pain), the PtGA of arthritis showed an increase of 1 or more grades and the PGA of arthritis showed an increase of 1 or more grades | Quantitative | African American patients aged ≥ 45 yrs, with OA of the knee (according to ACR criteria) in a flare state, and with a physician-classified functional capacity of I–III |
Sands, et al22 | Clinical trial | Design | From original paper (Strand, et al23): reported a score ≥ 4 but < 9 on the pain NRS and an increase ≥ 1 grade on the PtGA of arthritis to “fair, poor, or very poor” between screening (visit 1) and flare (visit 2), and a score of “fair, poor, or very poor” on the PGA of arthritis at visit 2 | Quantitative | Aged 18–80 yrs with knee or hip OA, determined by ACR criteria |
Gibofsky, et al24 | Clinical trial | Design | > 15 mm increase in WOMAC pain subscale score (on VAS) from screening to baseline | Quantitative | Men and women, clinically and radiographically confirmed hip and/or knee OA (KL grade II–III); ≥ 40 yrs of age, body weight ≥ 45 kg and a BMI < 40 kg/m2 |
Liu, et al25 | Clinical trial | Inclusion | ICOAP intermittent pain scale score > 0 + reporting unacceptable symptom state | Quantitative | Existing community cohort ≥ 45 yrs with hip or knee OA |
Bartholdy, et al26 | Exercise arm of clinical trial | Outcome | Knee pain above 5 on 0–10 NRS | Quantitative | Aged 40 yrs+, clinical diagnosis of knee OA confirmed by radiography, and BMI between 20 and 35 kg/m2 |
Altman, et al27 | Clinical trial | Design | ≥ 15 mm increase in WOMAC Pain score after discontinuation of NSAID/acetaminophen | Quantitative | ≥ 40 yrs of age; confirmed hip or knee OA; (KL grade II–III); chronic users of NSAID and/or acetaminophen; WOMAC pain score ≥ 40 mm |
OA: osteoarthritis; ACR: American College of Rheumatology; VAS: visual analog scale; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; KL: Kellgren-Lawrence arthritis grading scale; NRS: numerical rating scale; PtGA: patient’s global assessment; PGA: physician’s global assessment; NSAID: nonsteroidal antiinflammatory drug; BMI: body mass index; ICOAP: Intermittent and Constant Osteoarthritis Pain score; ARA: American Rheumatism Association; COX-2: cyclooxygenase-2.