Determinants of radiographic progression in early psoriatic arthritis: insights from a real-world cohort.

OBJECTIVE: Persistent articular inflammation in psoriatic arthritis (PsA) is associated with radiographic damage. Despite advances in diagnosis and therapy, radiographic structural damage remains prevalent in PsA. To elucidate this topic, we studied which baseline clinical characteristics determine radiographic progression. METHODS: For this analysis, data were used from DEPAR (Dutch South West Psoriatic Arthritis) Study, a real-world cohort of patients with newly diagnosed PsA. Radiographic changes were assessed using the modified Total Sharp/van der Heijde Score (mTSS) for PsA. Univariable-multivariable mixed-effects negative binomial regression analysis was applied to define baseline predictors for radiographic progression over time. RESULTS: The study included 476 patients with early PsA with 1660 hand and feet radiographs from four different time points (baseline, first, second and third year). The progressive group (n=71) had a higher mTSS compared with the non-progressive group (n=405) at diagnosis (17 (3-36) vs 0 (0-1)). A comparison of the two groups revealed that the progressive group had significantly older (59 (12) vs 49 (13)) and a higher rate of the presence of swollen joints (93% vs 78%) at diagnosis. Multivariable analysis identified age (incidence rate ratio (IRR)=1.10, p=0.000), sex (female) (IRR=0.48, p=0.043) and baseline mTSS (IRR=1.11, p=0.000) as significant determinants of radiographic change over time. For the progressive subset, additionally, the multivariable analysis highlighted baseline Disease Activity in PSoriatic Arthritis (IRR=1.05, p=0.006) and swollen joint count (IRR=1.07, p=0.034) as predictors. CONCLUSIONS: According to this real-world cohort, patients with early PsA exhibit minimal radiographic progression under current treatment protocols. This study indicates that while old age and initial radiographic damage predict progression, female sex confers a protective effect on it. Furthermore, disease activity score and swollen joints emerged as predictors for radiographic changes during the follow-up in progressive patients.

Window of opportunity in psoriatic arthritis: the earlier the better?

OBJECTIVES: To investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay. METHODS: All newly diagnosed, disease-modifying antirheumatic drug-naïve PsA patients who participated in the Dutch southwest Early PsA cohoRt and had ≥3 years of follow-up were studied. First, total delay was calculated as the time period between symptom onset and PsA diagnosis made by a rheumatologist and then split into patient and physician delays. The total delay was categorised into short (<12 weeks), intermediate (12 weeks to 1 year) or long (>1 year). These groups were compared on clinical (Minimal Disease Activity (MDA) and Disease Activity index for PSoriatic Arthritis (DAPSA) remission) and patient-reported outcomes during 3 years follow-up. RESULTS: 708 PsA patients were studied of whom 136 (19%), 237 (33%) and 335 (47%) had a short, intermediate and long total delay, respectively. Patient delay was 1.0 month and physician delay was 4.5 months. Patients with a short delay were more likely to achieve MDA (OR 2.55, p=0.003) and DAPSA remission (OR 2.35,p=0.004) compared with PsA patients with a long delay. Patient-reported outcomes showed numerical but non-significant differences between the short and long delay groups. Female patients and those presenting with enthesitis, chronic back pain or normal C-reactive protein (CRP) had a longer delay. CONCLUSIONS: In PsA, referral and diagnosis within 1 year is associated with better clinical outcomes, suggesting the presence of a window of opportunity. The most gain in referral could be obtained in physician delay and in females, patients with enthesitis, chronic back pain or normal CRP.

Validity, reliability, responsiveness and feasibility of four hand mobility measures in hand osteoarthritis.

OBJECTIVES: To investigate metric properties of four hand mobility tests in hand OA patients, using the OMERACT filter. METHODS: Trained assessors examined the Hand Mobility in Scleroderma test (HAMIS), fingertip-to-palm distance (FPD), modified Kapandji index (MKI) and number of hand joints with limited mobility in participants from two cohorts [Genetics ARthrosis and Progression (n = 207) and Hand OSTeoArthritis in Secondary care (n = 174)]. Validity was appraised by assessment of correlations with other outcome measures, and ability to measure thumb vs finger mobility specifically, using cumulative probability plots. The proportion of participants changing in hand mobility based on the smallest detectable difference was calculated for responsiveness. Intraclass correlation coefficients (ICCs) for intra- and interobserver reliability, and feasibility (time to perform tests) were studied in a random sample (n = 20). RESULTS: Participants displayed large variation in mobility scores. Strongest correlations were observed with structural damage (rs = 0.43-0.52) and bony swelling (rs = 0.46-0.58); correlation patterns were similar among tests. HAMIS, FPD and MKI could all measure finger mobility specifically, but only HAMIS measured thumb mobility particularly. Interobserver reliability was best for HAMIS, ICC 0.90 (95% CI: 0.76, 0.96); intraobserver reliability was excellent for all (ICCs 0.94-0.97). In 2 years, little change was observed; HAMIS was the most sensitive-to-change (smallest detectable difference 3.7% of maximum score). The mean performance time ranged from 0.7 (s.d. 0.5, for FPD) to 5.7 (s.d. 1.3, for HAMIS) min. CONCLUSION: HAMIS, FPD, MKI and number of joints with limited mobility are all valid, reliable and feasible measures for assessing hand mobility in hand OA, although HAMIS had slightly more favourable properties. Studies assessing sensitivity-to-change in a clinical trial setting are warranted.

Clustering of hand osteoarthritis progression and its relationship to progression of osteoarthritis at the knee.

OBJECTIVE: To investigate patterns of osteoarthritis (OA) progression within hand joints and the relationship between hand OA progression and progression of OA at the knee. METHODS: Radiographic progression over 6 years, defined as change in osteophytes or joint space narrowing above the smallest detectable change, was assessed on hand and knee radiographs of 236 hand OA patients participating in the Genetics, Arthrosis and Progression (GARP) sibling pair cohort study using OARSI atlas. Clustering of radiographic progression between hand joint groups (DIP, PIP, IP-1 and CMC-1) was assessed using χ(2) test. Symmetry, clustering by row and ray and familial aggregation in sibling pairs were also evaluated. The association between hand OA progression and progression of OA at the knee was assessed using generalised estimating equation analysis. RESULTS: There was clustering of OA progression between hand joint groups, the strongest relationship among DIP, PIP and IP-1 joints. Other patterns were symmetry (OR 4.7 (95% CI 3.3 to 6.5)) and clustering by row (OR 2.9 (95% CI 1.9 to 4.6)) but not by ray (OR 1.3 (95% CI 0.7 to 2.4)). There was familial aggregation of hand OA progression. Patients with progression of hand OA had a higher risk for radiographic change at the knee than those without hand OA progression (OR 2.3 (95% CI 1.3 to 4.0)). CONCLUSIONS: Progression of hand OA clusters between hand joint groups, especially between IP joints, and within sibling pairs. It is associated with OA change at the knee. These findings contribute to defining hand OA subsets and suggest a role for systemic factors.

Comparison of features by MRI and radiographs of the interphalangeal finger joints in patients with hand osteoarthritis.

OBJECTIVES: To examine the construct validity of MRI in the detection of structural hand osteoarthritis features with conventional radiography (CR) as reference and explore the association between radiographic severity and MRI-defined pathology. METHODS: 106 hand osteoarthritis patients (97 women, mean age 68.9 years (SD 5.6)) had 1.0T contrast-enhanced MRI and CR of the dominant hand. The 2nd-5th interphalangeal joints were scored according to the preliminary Oslo hand osteoarthritis MRI score and Kellgren-Lawrence (KL) scale and Osteoarthritis Research Society International atlas for radiographs. The authors compared the number of joints with structural features by MRI and CR (Wilcoxon signed-rank test) and examined concordance at the individual joint level. The OR of MRI features in joints with doubtful (KL grade 1), mild (2) and moderate/severe (≥3) radiographic osteoarthritis was estimated by generalised estimating equations (KL grade 0 as reference). RESULTS: MRI detected approximately twice as many joints with erosions and osteophytes compared with CR (p<0.001), but identification of joint space narrowing, cysts and malalignment was similar. The sensitivity of MRI was very high for osteophytes (1.00) and erosions (0.95), while specificity was lower (0.22 and 0.63). The prevalence of most MRI features increased with radiographic severity, but synovitis was more frequent in joints with mild osteoarthritis (OR2.1, 95% CI 1.4 to 3.2) than in moderate/severe osteoarthritis (OR1.4, 95% CI 1.0 to 2.2). CONCLUSION: MRI detected more osteophytes and erosions than CR, suggesting that erosive osteoarthritis may be more common than indicated by CR. Synovitis was most common in mild osteoarthritis. Whether this is due to burn-out of inflammation in late disease must be investigated further.

Association between several clinical and radiological determinants with long-term clinical progression and good prognosis of lower limb osteoarthritis.

OBJECTIVE: To investigate the factors associated with clinical progression and good prognosis in patients with lower limb osteoarthritis (OA). METHODS: Cohort study of 145 patients with OA in either knee, hip or both. Progression was defined as 1) new joint prosthesis or 2) increase in WOMAC pain or function score during 6-years follow-up above pre-defined thresholds. Patients without progression with decrease in WOMAC pain or function score lower than pre-defined thresholds were categorized as good prognosis. Relative risks (RRs) for progression and good prognosis with 95% confidence interval (95% CI) were calculated by comparing the highest tertile or category to the lowest tertile, for baseline determinants (age, sex, BMI, WOMAC pain and function scores, pain on physical examination, total range of motion (tROM), osteophytes and joint space narrowing (JSN) scores), and for worsening in WOMAC pain and function score in 1-year. Adjustments were performed for age, sex, and BMI. RESULTS: Follow-up was completed by 117 patients (81%, median age 60 years, 84% female); 62 (53%) and 31 patients (26%) showed progression and good prognosis, respectively. These following determinants were associated with progression: pain on physical examination (RR 1.2 (1.0 to 1.5)); tROM (1.4 (1.1 to 1.6); worsening in WOMAC pain (1.9 (1.2 to 2.3)); worsening in WOMAC function (2.4 (1.7 to 2.6)); osteophytes 1.5 (1.0 to 1.8); and JSN scores (2.3 (1.5 to 2.7)). Worsening in WOMAC pain (0.1 (0.1 to 0.8)) and function score (0.1 (0.1 to 0.7)), were negatively associated with good prognosis. CONCLUSION: Worsening of self-reported pain and function in one year, limited tROM and higher osteophytes and JSN scores were associated with clinical progression. Worsening in WOMAC pain and function score in 1- year were associated with lower risk to have good prognosis. These findings help to inform patients with regard to their OA prognosis.

Association between leptin, adiponectin and resistin and long-term progression of hand osteoarthritis.

OBJECTIVE: To investigate the association between baseline serum adipokines levels-leptin, adiponectin and resistin-and long-term progression of hand osteoarthritis (HOA). METHODS: Baseline and 6-year radiographs of 164 patients (mean age 60 years, 81% women) with HOA (defined as a Kellgren and Lawrence score ≥2 in at least two hand joints) were assessed for joint space narrowing (JSN) in 32 hand joints using the Osteoarthritis Research Society International atlas. Progression was defined as a change in the sum of the JSN score above the smallest detectable change of 2, reflecting change above measurement error. Serum adipokines were measured at baseline and patients were categorised by adipokine tertiles. RRs (and 95% CI) of HOA progression for patients in the second and third tertiles were calculated relative to the first tertile, using generalised estimating equations. Adjustments were made for age, sex and body mass index. RESULTS: Patients in the two highest tertiles of adiponectin had a decreased risk of 70% (RR=0.3 (0.2 to 0.7)) for HOA progression in comparison with patients in the lowest tertile. Leptin and resistin levels were not associated with progression. CONCLUSION: Adiponectin levels are associated with progression of HOA, suggesting that adiponectin may be involved in the pathophysiology of OA.

Thumb base involvement in symptomatic hand osteoarthritis is associated with more pain and functional disability.

OBJECTIVE: To assess the impact of different subsets of symptomatic hand osteoarthritis (OA) on pain and disability. METHODS: From 308 patients with hand OA a group with carpometacarpal joint (CMCJ) symptoms only (group I, n=20) was identified as well as groups with symptoms at the interphalangeal joints (IPJs) only (group II, n=138), and symptoms at both sites (group III, n=150). Hand pain and function, assessed with the AUSCAN, were compared between groups using linear mixed models. Radiological OA was assessed using the Kellgren-Lawrence grading scale. RESULTS: Mean (SD) AUSCAN scores for groups I, II and III were 23.1 (11.7), 18.3 (11.9) and 26.4 (12.5), respectively. After adjustment for age, gender, body mass index, family effects and number of symptomatic hand joints, significant differences in AUSCAN scores of 7.4 (95% CI 1.8 to 13.0) between groups I and II, and 5.7 (95% CI 2.7 to 8.6) between groups II and III were found. AUSCAN scores were 5.8 (95% CI 3.1 to 8.6) higher for patients with versus patients without CMCJ symptoms. Kellgren-Lawrence scores did not differ between groups. CONCLUSION: In symptomatic hand OA, CMCJ OA contributes more to pain and disability than IPJ OA. Hence, treatment of CMCJ OA should be emphasised, even if it coincides with IPJ OA.

Using the common sense model of illness perceptions to examine osteoarthritis change: a 6-year longitudinal study.

OBJECTIVE: To examine the association between changes in common sense models and changes in functional status over a 6-year follow-up in patients with osteoarthritis. DESIGN: At baseline and follow-up, osteoarthritis outpatients (N = 241) recruited from a university medical center completed the Illness Perception Questionnaire-Revised (IPQ-R), the Australian/Canadian Osteoarthritis Hand Index, and the Western Ontario and McMasters Universities Osteoarthritis Index. Also, their physician-assessed pain intensity, and biomedical, and clinical measures of medical severity of osteoarthritis were recorded. MAIN OUTCOME MEASURES: Functional disability, pain intensity. RESULTS: Over 6 years, functional disability and pain intensity increased. The IPQ-R dimensions of timeline, personal control, and illness coherence became more negative, and emotional representations became less negative (i.e., more accepting). Patients identified as sharing a similar profile of negative changes on the IPQ-R had significantly worse functioning on 2 of 3 outcomes, independent of objectively measured osteoarthritis severity. CONCLUSIONS: Changes in illness perceptions were associated with changes in outcomes. Interventions to prevent increasingly negative patterns of illness perceptions over time, with an emphasis on strengthening control cognitions, may benefit functional status outcomes in patients with osteoarthritis.

Familial influence on tibiofemoral alignment.

BACKGROUND: Tibiofemoral alignment has a role in knee osteoarthritis (OA), but which factors contribute to alignment is unknown. OBJECTIVE: To investigate familial aggregation of tibiofemoral alignment in participants of the GARP (Genetics ARthrosis and Progression) study. METHODS: The tibiofemoral anatomical angle on semiflexed knee radiographs was measured in sibling pairs (mean age 60 years, 81% women) with primary OA with multiple joint involvement. Radiographic OA was assessed according to the Kellgren-Lawrence (KL) method. Heritability estimates of the tibiofemoral angle were calculated by comparing twice the between-sibling variance with the total variance; adjustments were made for age, gender, body mass index, history of meniscectomy, lower limb fracture and in analyses including all knees, for KL score. RESULTS: 360 subjects representing 180 families were studied. The mean (SD) tibiofemoral angle of right and left knees in the probands was 182.7 (2.9) degrees and 182.8 (2.6) degrees , respectively; similar angles were measured in the siblings. Radiographic knee OA (KL score > or =2) was present in 27% of the knees. Stratified analyses in sib pairs with non-osteoarthritic right or left knees showed adjusted heritability estimates of the tibiofemoral angle of the right and left knees of 0.42 (95% CI 0.02 to 0.82) and 0.56 (95% CI 0.19 to 0.93). In addition, adjusted heritability estimates of the tibiofemoral angle in all right and left knees were calculated, being 0.48 (95% CI 0.18 to 0.78) and 0.50 (95% CI 0.21 to 0.79), respectively. CONCLUSION: The alignment of the tibiofemoral joint is influenced by familial factors, implying that tibiofemoral malalignment may add to the genetic predisposition for knee OA development. These results need to be confirmed in other study populations.