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Objective Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA).Methods Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data.Results 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported.Conclusion In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.

Background/objective The aim of this study was to evaluate relative performance of composite measures in psoriatic arthritis and assess the impact of structural damage and functional disability on outcomes during ixekizumab treatment.Methods Data from SPIRIT-P1 and SPIRIT-P2 were analysed to evaluate the effect of ixekizumab on achievement of low disease activity (LDA) and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE and modified Composite Psoriatic Disease Activity Index (mCPDAI). Performance was compared by quantifying residual symptom burden and the impact of structural damage and functional disability.Results Significantly more ixekizumab-treated patients achieved treatment targets at week 24 versus placebo assessed with all composites. More patients achieved targets assessed by mCPDAI and DAPSA than other composites. Residual disease activity was similar between composites, but residual high patient-reported outcomes (PROs) and functional disability were more frequent when assessed with mCPDAI and DAPSA. Achievement of treatment targets was reduced by high baseline levels of structural damage and functional disability.Conclusion Residual disease activity was similar in patients achieving treatment targets assessed with all composites, but residual high PROs and functional disability were more common when assessed with mCPDAI and DAPSA, most likely due to the absence/attenuated functional assessment in these composites. High baseline levels of structural damage and functional disability attenuated response rates with all composites, affecting MDA/VLDA most prominently; LDA may be the most appropriate target in these patients.Trial registration number NCT01695239.

Objective We used the Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) data set to examine the impact of presence of enthesitis, dactylitis, nail disease and/or psoriasis on treatment response in patients with early psoriatic arthritis (PsA).Methods This post hoc analysis evaluated the effect of baseline Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index (EI), Leeds Enthesitis Index (LEI), Leeds Dactylitis Index (LDI), modified Nail Psoriasis Severity Index (mNAPSI) scores and body surface area (BSA) on composite outcomes of minimal disease activity (MDA) responses, Psoriatic Arthritis Disease Activity Score (PASDAS) low disease activity (LDA), PASDAS changes and Good Responses and Disease Activity Index for Psoriatic Arthritis (DAPSA) scores at Week 24.Results Overall, 851 patients completed the SEAM-PsA trial and were included in the analysis. Baseline enthesitis (SPARCC EI>0 vs SPARCC EI=0 or LEI>0 vs LEI=0) was not associated with improved outcomes. Baseline dactylitis (LDI>0 vs LDI=0) was positively associated with improved MDA (OR: 1.4, p=0.0457), PASDAS LDA (OR: 1.8, p=0.0014) and Good Responses (OR: 1.6, p=0.0101) and greater reductions in PASDAS (estimate: –0.9, p1 vs mNAPSI≤1) was positively associated with improved MDA (OR: 1.8, p=0.0233) and PASDAS LDA (OR: 1.8, p=0.0168) responses and greater reduction in PASDAS (estimate: –0.7, p=0.0005) at Week 24.Conclusions Results from our analysis suggest that presence of dactylitis and nail disease, but not enthesitis, are associated with improved outcomes in patients with early PsA who were treated with methotrexate and/or etanercept.

Objectives This post-hoc analysis explored the impact of body mass index (BMI) on tofacitinib efficacy/safety in patients with active psoriatic arthritis (PsA).Methods Data were pooled from two phase 3 studies (NCT01877668; NCT01882439). Analyses included patients randomised to tofacitinib 5/10 mg two times a day or placebo, stratified by baseline BMI:

Objective Evaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year.Methods Adults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab 100 mg Q4W at Week24 (PBO→Q4W) through Week48. Clinical efficacy through Week52 (employing non-responder imputation) and adverse events (AEs) through Week60 were evaluated.Results Of 381 treated patients, 90% completed the study. Numerical increases in the proportions of patients achieving ≥20% improvement in ACR criteria (ACR20) were observed post-Week24, reaching 73% (94/128) and 60% (76/127) for Q4W-randomised and Q8W-randomised patients, respectively, by Week52. Proportions of patients achieving ACR50/ACR70/skin responses and minimal/very low disease activity were maintained, as were improvements in physical function and health-related quality of life, through Week52 in guselkumab-randomised patients. Response to guselkumab was maintained in both TNFi-naïve and TNFi-experienced patients. Serious AEs and serious infections occurred in similar proportions of guselkumab Q4W-randomised (3% and 0%) and Q8W-randomised (6% and 2%) patients through Week60, with no new safety concerns versus observations through Week24. No guselkumab-treated patient and two patients receiving placebo died; no study participant developed opportunistic infection or inflammatory bowel disease.Conclusion Guselkumab provided sustained improvement across multiple clinical manifestations of PsA, maintaining a favourable benefit-risk profile, through 1 year regardless of prior TNFi exposure.

Objective To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA).Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses.Results Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24).Conclusions At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis.Trial registration number ClinicalTrials.gov: NCT02319759.URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.

Background The interleukin-12/23p40-subunit-inhibitor ustekinumab significantly improved spondylitis-related symptoms through Week 24 in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (PA-PRS) in PSUMMIT-1&2. We further evaluated ustekinumab’s effect on spondylitis-related endpoints in PSUMMIT-1&2 tumour necrosis factor-inhibitor (TNFi)-naïve patients with PA-PRS.Methods Patients with active PsA (≥5 swollen and ≥5 tender joints, C-reactive-protein ≥ 3.0 mg/L) despite conventional (PSUMMIT-1&2) and/or prior TNFi (PSUMMIT-2) therapy received subcutaneous ustekinumab 45 mg, 90 mg or placebo (Week 0, Week 4, Week 16). Changes in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) neck/back/hip pain question (#2) and modified BASDAI (mBASDAI, excluding PA) scores and Ankylosing Spondylitis Disease Activity Score (ASDAS) responses were assessed at Weeks 12 and 24.Results The pooled PSUMMIT-1&2, TNFi-naïve (n=747), PA-PRS (n=223) subset (158 with human-leucocyte-antigen (HLA)-B27 results) presented with moderate-to-severe spondylitis-related symptoms (mean BASDAI-neck/back/hip pain-6.51, mBASDAI-6.54, BASDAI-6.51, ASDAS-3.81). Mean Week 24 changes were larger among ustekinumab than placebo-treated patients for both neck/back/hip pain (−1.99 vs −0.18) and mBASDAI (−2.09 vs −0.59). Improvements in neck/back/hip pain and fatigue appeared numerically greater in HLA-B27+ than HLA-B27– patients; those for other domains were generally consistent. Greater proportions of ustekinumab versus placebo-treated patients achieved ASDAS clinically important improvement at Week 24 (decrease ≥ 1.1; 49.6% vs 12.7%; nominal p

A study was conducted to compare the gait pattern of 12 patients with ankylosing spondylitis with axial disease only with that of 11 healthy controls using a telemeterised electrogoniometer gait analysis system. The reproducibility of the gait variables was found to be acceptable. Angles for movement at the hip and knee were less in patients with ankylosing spondylitis, but hip/knee angle ratios did not differ between the two groups. The stride length was shorter in the patients with ankylosing spondylitis. These findings are due to the increased rigidity of the spine, which results in decreased shock absorption and consequently a more cautious gait pattern in the absence of clinically and radiologically detectable peripheral joint disease. [ABSTRACT FROM PUBLISHER]

Objectives In disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis (RA), to compare the efficacy of methotrexate (MTX) and infliximab (IFX) with MTX and intravenous corticosteroid for remission induction. Methods In a 78-week multicentre randomised controlled trial, double-blinded to week 26, 112 treatment-naive RA patients (1987 American College of Rheumatology classification criteria) with disease activity score 44 (DAS44)>2.4 were randomised to MTX + IFX or MTX + single dose intravenous methylprednisolone 250 mg. A treat-to-target approach was used with treatment escalation if DAS44>2.4. In the IFX group, IFX was discontinued for sustained remission (DAS44<1.6 for 6 months). The primary outcome was change in modified total Sharp-van der Heijde score (mTSS) at week 50. Results The mean changes in mTSS score at week 50 in the IFX and intravenous steroid groups were 1.20 units and 2.81 units, respectively (adjusted difference (95% CI) -1.45 (-3.35 to 0.45); p=0.132). Radiographic nonprogression (mTSS<2.0) occurred in 81% vs 71% (OR 1.77 (0.56 to 5.61); p=0.328). DAS44 remission was achieved at week 50 in 49% and 36% (OR 2.13 (0.91 to 5.00); p=0.082), and at week 78 in 48% and 50% (OR 1.12 (0.47 to 2.68); p=0.792). Exploratory analyses suggested higher DAS28 remission at week 6 and less ultrasound synovitis at week 50 in the IFX group. Of the IFX group, 25% (14/55) achieved sustained remission and stopped IFX. No substantive differences in adverse events were seen. Conclusions In DMARD-naive early RA patients, initial therapy with MTX+high-dose intravenous steroid resulted in good disease control with little structural damage. MTX +IFX was not statistically superior to MTX+intravenous steroid when combined with a treat-to-target approach. [ABSTRACT FROM AUTHOR]

Objective: In 1971 McEwen and colleagues suggested that the radiological changes of classic ankylosing spondylitis (AS), and the changes of the spondylitis associated with inflammatory bowel disease differ in several respects from the radiological features of psoriatic and reactive spondylitis. The findings of this study have never been confirmed. The aim of this study was to replicate the McEwen study comparing films blinded to diagnostic group.Methods: The study population comprised 91 patients with classic AS, 15 patients with regional enteritis, 16 patients with ulcerative colitis, five patients with sexually acquired reactive arthritis, two with post-dysenteric arthritis, and 34 with psoriatic arthritis. Blinded reading of spinal radiographs was undertaken, scoring for severity, symmetry, paravertebral ossification, size of syndesmophytes, ligamentous calcification, squaring, discitis, pseudofractures, zygoapophyseal joint involvement, and complete ankylosis.Results: Comparison of the four groups--classic, enteropathic, psoriatic, and reactive AS--showed differences with respect to symmetry of sacroiliitis, symmetry of lumbar spinal involvement, and frequency and size of syndesmophytes. Zygoapophyseal joint involvement was more frequent in the lumbar spine in classic and enteropathic spondylitis but no between group differences were found with respect to symphisitis, squaring, apophyseal joint involvement and ligamentous calcification in the lumbar spine, and other areas.Conclusions: Some of the radiological differences described by McEwen et al, notably the asymmetry, the less severe changes, and the distinctive syndesmophytes in psoriasis, have been confirmed. A number of phypotheses are proposed to explain these differences including biomechanical, biochemical, and genetic factors. [ABSTRACT FROM AUTHOR]

Investigates the relation of heel position and distribution of forefoot plantar pressures and skin callosities in rheumatoid arthritis. Comparison of peak pressures in the rheumatoid normal heel with rheumatoid valgus heel group; Inability of lateral metatarsal heads to bear weight in rheumatoid valgus heel group.

Objectives: To establish consensus case definitions for several common work related upper limb pain syndromes for use in surveillance or studies of the aetiology of these conditions.Methods: A group of healthcare professionals from the disciplines interested in the prevention and management of upper limb disorders were recruited for a Delphi exercise. A questionnaire was used to establish case definitions from the participants, followed by a consensus conference involving the core group of 29 people. The draft conclusions were recirculated for review.Results: Consensus case definitions were agreed for carpal tunnel syndrome, tenosynovitis of the wrist, de Quervain's disease of the wrist, epicondylitis, shoulder capsulitis (frozen shoulder), and shoulder tendonitis. The consensus group also identified a condition defined as "non-specific diffuse forearm pain" although this is essentially a diagnosis made by exclusion. The group did not have enough experience of the thoracic outlet syndrome to make recommendations.Conclusions: There was enough consensus between several health professionals from different disciplines to establish case definitions suitable for use in the studies of several work related upper limb pain syndromes. The use of these criteria should allow comparability between studies and centres and facilitate research in this field. The criteria may also be useful in surveillance programmes and as aids to case management. [ABSTRACT FROM AUTHOR]

Repetitive strain injury, or work related upper limb disorder, provides an interesting paradigm for the study of the relative contribution of physical and psychological factors to the resulting pain and disability. Sixty three subjects were studied, comprising the work-force of a subsection of a large local industrial company, in whom pain in the arm related to work was known to be common. Ergonomic data were obtained by estimating the cumulative daily load on the wrist joint for each of four identified tasks. Data on the occurrence of pain, treatment sought, and disability were obtained by a structured self administered questionnaire. Psychological data were obtained by administering the Hospital Anxiety and Depression (HAD) scale, a self reported measure of anxiety and depression, and the Bradford Somatic Inventory (BSI), an inventory of somatic symptoms associated with anxiety and depression. The employment specific period prevalence of work related upper limb disorder was 81%, with 30% of the subjects having pain at the time of the study. Domestic disability was minimal in all but two subjects, though the use of devices such as jar openers at home was common (12 of 51 subjects). Medical advice was seldom sought. Twenty per cent of subjects had received anti-inflammatory drugs, 10% had received physiotherapy, and 47% had wrist splints. Pain was related to the tasks with the highest estimated daily loads, but a history of pain and current pain were associated with higher scores on the HAD and BSI scales, suggesting an interaction between physical and psychological factors. [ABSTRACT FROM PUBLISHER]

Cytidine deaminase activity, C reactive protein, histidine, and erythrocyte sedimentation rate were measured in 36 subjects with psoriatic arthritis of varying disease duration and severity. Although cytidine deaminase activity may provide an integrated measure of synovial inflammation in rheumatoid arthritis, neutrophil accumulation in psoriatic plaques compromises this measure in psoriatic arthritis. Low histidine concentrations confirm that this amino acid provides a non-specific index of synovial inflammation. In psoriatic arthritis high C reactive protein concentrations seem to be associated with extensive joint destruction. In this study the erythrocyte sedimentation rate was found to be the best laboratory guide to clinical disease activity in psoriatic arthritis. [ABSTRACT FROM PUBLISHER]

A strain gauged torsion dynamometer linked to a microprocessor was used to assess the dynamic qualities of isometric grip strength in patients with rheumatic diseases. Maximum grip strength, time to maximum grip, and percentage fatigue provide independent information on the grip. Time to maximum grip does not appear to be an objective correlate of subjective stiffness. The usefulness of these dynamic variables for the assessment of stiffness appears limited in arthritic disease, where pain may interfere with the maximum voluntary effort of the test. [ABSTRACT FROM PUBLISHER]

Metacarpophalangeal joint stiffness was measured using a new microprocessor controlled arthrograph in 135 patients with rheumatoid arthritis. Subjects were prospectively subdivided according to the stage of the disease in the joint. Compared with a normal population stiffness variables in active rheumatoid arthritis were decreased, significantly so for non-elastic stiffness. This study casts doubts on the literal interpretation of symptomatic stiffness as an indicator of disease activity in rheumatoid arthritis and suggests a number of explanations for the discordant result. [ABSTRACT FROM PUBLISHER]

Studies the subjective improvement in joint stiffness following intra-articular injection of corticosteroid. Beneficial effect of corticosteroid in synovial inflammation; Adverse effects; Similarity with monosodium urate crystals; Objective measure of joint stiffness; Changes seen after 24 hours.

Examines the intended meaning of words used by patients to describe arthritic symptoms. Discrimination between different patient groups on the basis of symptom description; Patient categorization of descriptors; Use of descriptors between different diseases.

Objective: To relate weakness of grip to loss of forearm muscle bulk, hand joint deformity, and hand joint tenderness in patients with rheumatoid arthritis (RA).Methods: Using anthropometric data we have estimated the anatomical cross-sectional area (CSA) of forearm muscles in 100 subjects with RA compared with 100 aged and sex-matched normal subjects. We also recorded hand joint tenderness using a modification of the Ritchie articular index, and a simple index of hand joint deformity.Results: We found a significant reduction in anatomical CSA in RA (forearm CSA in normal subjects 29.7 cm2 and in RA 25.9 cm2; p = 0.002). In simple linear regression we found that 46.3% of the variation in grip strength in normal subjects was explained by variation in muscle CSA; in RA this figure decreased to 33.4%. Adding terms for joint deformity and pain in a multiple regression model improved the amount of variation explained to 37.9%.Conclusions: Although there is significant muscle wasting in RA, it is likely that reduction in strength is also attributable to joint deformity and pain leading to inhibition of grip directly and, indirectly, by arthrogenous muscle inhibition. Doubts remain about the quality of muscle in RA. [ABSTRACT FROM AUTHOR]

The case is presented of a patient with mild rheumatoid arthritis who developed an enlarged painful tissue mass in the left lower leg. Although the history, clinical, and imaging appearances suggested that it was a soft tissue sarcoma, a biopsy specimen showed histological features consistent with either a rheumatoid nodule or subcutaneous granuloma annulare. [ABSTRACT FROM PUBLISHER]