BackgroundPsoriatic arthritis (PsA) is typically described by its individual domains or clinical components.1,2ObjectivesThis post hoc analysis aimed to identify hypothesis-free phenotype clusters according to patients’ clinical features and baseline (BL) characteristics with data from the Phase 3 DISCOVER-1 and -2 guselkumab (GUS) clinical trials.MethodsData from bio-naïve patients with PsA treated with GUS 100 mg every 4 or 8 weeks in DISCOVER-1 and -2 were retrospectively analysed. Non-negative matrix factorisation was used as an unsupervised machine learning technique to identify clusters of PsA phenotypes, with BL characteristics and clinical observations as input features, according to which clusters were described.ResultsData from 661 patients were pooled and 8 distinct clusters of PsA phenotypes identified (Table 1). Cluster 1 was characterised by lower limb involvement and the lowest rates of severe skin involvement (Figure 1); Cluster 2 by high skin involvement, the lowest proportion of women and highest proportion of overweight patients (body mass index [BMI] 25–<30, 70%); and Cluster 3 by high burden of disease in the hand/wrist. In Cluster 4 all patients had dactylitis and ≥3% body surface area (BSA) psoriasis involvement and the second highest proportion of men. Cluster 5 had the highest BL enthesitis rate; large joint involvement was also common. Cluster 6 had a high level of small joint involvement in the hands/feet, but low mean dactylitis score; nail involvement and BL enthesitis were also common. In Cluster 7, all patients had axial involvement at BL, 49.4% had dactylitis, 69.9% had enthesitis and most had BSA ≥3% (Figure 1). Cluster 8 had limited joint involvement, extensive skin involvement and the highest proportion of obese patients (BMI >30, 67%). Minimal disease activity (MDA) response rates at Week (W)24 and W52 were highest in Cluster 2 and lowest in Cluster 5. Clusters 3 and 4 had low MDA response rates at W24, increasing at W52.Table 1.Baseline characteristics of PsA phenotype clusters.Cluster 1Cluster 2Cluster 3Cluster 4Cluster 5Cluster 6Cluster 7Cluster 8Feet dominantMale, overweight, psoriasis burdenHand dominantDactylitis dominantEnthesitis and large jointsEnthesitis and small jointsAxial dominantFemale, obese, large jointsRandomised and treated patients, n791259538576083124Age, years45.8 (10.4)45.8 (13.2)48.9 (11.8)44.8 (12.3)43.6 (13.3)45.8 (11.6)43.8 (10.4)47.5 (11.1)Female %54.420.060.026.364.941.736.161.3BMI, kg/m229.3 (5.4)27.4 (3.6)29.3 (6.1)26.9 (4.6)28.6 (7.5)29.0 (6.2)28.4 (6.9)32.1 (6.5)CRP, mg/dL1.7 (1.8)1.7 (2.0)1.4 (2.3)2.5 (2.8)1.7 (1.9)1.7 (1.8)2.2 (3.1)1.5 (1.8)Disease duration, years5.0 (5.3)5.1 (4.8)5.8 (6.5)6.1 (5.5)6.8 (7.6)6.1 (5.6)4.7 (4.6)5.2 (6.7)SJC, 0–6613.2 (7.1)8.2 (3.8)15.0 (8.0)18.0 (10.1)10.1 (5.1)17.5 (11.8)9.0 (4.2)8.8 (3.9)TJC, 0–6823.4 (10.1)12.8 (5.9)26.0 (12.0)30.6 (15.3)23.2 (12.6)37.5 (18.6)14.6 (6.5)12.7 (5.2)BSA, %12.6 (19.4)20.7 (19.8)14.8 (19.5)29.7 (26.4)14.6 (21.6)14.5 (18.4)15.2 (19.4)14.4 (15.7)Dactylitis %48.130.442.1100.036.853.349.431.5Dactylitis score3.0 (4.8)1.4 (3.2)2.7 (4.8)27.5 (12.3)2.3 (5.2)3.9 (6.8)2.2 (2.9)1.3 (2.5)Enthesitis %70.949.658.981.696.573.369.945.2LEI score2.0 (1.7)1.0 (1.3)1.7 (1.8)2.9 (1.9)4.2 (1.6)2.7 (2.3)1.3 (1.2)1.0 (1.3)Data shown are mean (standard deviation) or %. Bold font indicates differentiating features of individual clusters. BMI, body mass index; BSA, body surface area; CRP, C-reactive protein; LEI, Leeds Enthesitis Index; PsA, psoriatic arthritis; SJC, swollen joint count; TJC, tender joint count.ConclusionUnsupervised machine learning identified 8 clusters of PsA phenotypes with significant differences in demographic and clinical features, including patterns of domain involvement and MDA responses. These clusters differ in their initial vs. later responses to GUS.References[1]Coates C et al. Arthritis Rheumatol 2016; 68: 1060–1071.[2]Gossec L et al. Ann Rheum Dis 2012; 71: 4–12.Disclosure of InterestsPascal Richette Speakers bureau:, Consultant of: Pascal Richette has received fees from AbbVie, Amgen, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer and UCB., Marijn Vis Speakers bureau:, Consultant of:, Grant/research support from: Marijn Vis has received research grants, consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation., Sarah Ohrndorf Speakers bureau: Sarah Ohrndorf has received speaker fees or travel expense reimbursements from AbbVie, BMS, Janssen, Novartis and Pfizer., William Tillett Speakers bureau:, Consultant of:, Grant/research support from: William Tillett has received research grants, consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB., Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen, Michel van Speybroeck Shareholder of: Johnson & Johnson, Employee of: Janssen, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen, Alen Zabotti Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis and UCB, Grant/research support from: Novartis

Rheumatologic disorders comprise various conditions having different etiologies and pathogenesis, the leading clinical symptoms of which are chronic joint pain and musculoskeletal impairment. In the context of a multimodal therapy concept, the use of hyperthermia (HT) is a classical and developing adjuvant symptomatic treatment option. wIRA is an effective and well-established variant of thermal therapy in different rheumatologic disorders. This article summarizes the current state of research into locally applied wIRA in the field of rheumatism and rheumatological diseases.Local and serially applied wIRA significantly relieves pain in patients with axial spondyloarthritis (axSpA), osteoarthritis (OA) and fibromyalgia (FM), which, at least reduces the requirement for analgesics and has positive effects on well-being, functional status or disease activity. wIRA has been shown to reduce levels of C-reactive protein (CRP) and proinflammatory cytokine tumour necrosis factor α (TNFα). Given its safety and tolerability, wIRA is highly amenable in combination with standard therapies.Currently, wIRA effects are assessed in OA patients, non-inflammatory arthralgia and recent-onset arthritis of the hands. Preliminary data on effects on pain, global disease burden and functional status are promising. The potential value of wIRA, for e.g., Raynaud’s phenomena and sclerotic skin changes, need further evaluation.

BackgroundGuselkumab (GUS) is a human monoclonal antibody targeting the interleukin-23p19-subunit. It has demonstrated efficacy at Week 24 in the Phase IIIb COSMOS clinical trial of patients with active psoriatic arthritis (PsA) and inadequate response or intolerance to one or two tumour necrosis factor inhibitors (TNFis).1ObjectivesThe aim of this post hoc analysis was to identify predictors of minimal disease activity (MDA) with GUS at Week 24 in patients with active PsA and inadequate response or intolerance to one or two TNFis.MethodsA multiple logistic regression analysis was performed to identify potential predictors of MDA with GUS at Week 24 in TNFi-refractory patients with PsA. Odds ratios, 95% confidence intervals and p-values were calculated. Baseline characteristics assessed as predictors included age, sex, body mass index (BMI), C-reactive protein (CRP), other medication use and disease duration. Clinical features included tender and swollen joint counts (TJC/SJC), affected joint location, dactylitis, enthesitis, spondylitis, Psoriasis Area and Severity Index (PASI) score and psoriasis (PsO) localisation (Figure 1). Missing data for MDA at Week 24 were imputed as non-response; missing baseline values were imputed for two patients.Figure 1.Odds ratios and 95% CIs for potential predictors of minimal disease activity response to guselkumab 100 mg every 8 weeks at Week 24 in patients with PsA and an inadequate response or intolerance to one or two prior TNF inhibitors.BMI, body mass index; CI, confidence interval; CRP, C-reactive protein; csDMARD, conventional systemic disease-modifying anti-rheumatic drug; HAQ-DI, Health Assessment Questionnaire - Disability Index; MDA, minimal disease activity; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsO, psoriasis; TNF, tumour necrosis factor.N=187 for all clinical features and baseline characteristics. Negative predictors are indicated by bold text and positive predictors by italicisation (p<0.05).ResultsOf the 187 patients in this study, 54.6% were women and the mean disease duration was 8.3 years. The patients had a mean TJC 0–68 of 21.0, a mean SJC 0–66 of 10.3, a mean PASI score of 11.6 and a mean BMI of 28.9. Furthermore, 67.9% had enthesitis and 35.8% had dactylitis at baseline. One prior TNFi had been received by 88.2% of patients, and two received by 11.8%. At Week 24, 17.1% of patients (32/187) achieved MDA. Wrist involvement (p=0.031) and scalp PsO (p=0.049) were positive predictors of MDA. Women were significantly less likely to achieve MDA (p=0.036) than men; other negative predictors included involvement of shoulder or small joints of the hand, and hand/foot PsO (all p<0.05). Age, BMI, CRP, TJC/SJC, HAQ-DI, PASI, spondylitis, enthesitis, dactylitis, other medication use and number of prior TNFis were not predictive of MDA (Figure 1).ConclusionBaseline characteristics and clinical features may be positively (wrist involvement, scalp PsO) or negatively (female sex, involvement of shoulder or small joints of the hand, hand/foot PsO) associated with achieving MDA with GUS at Week 24 in a TNFi-refractory population. Though the low patient number limits the generalisability of this analysis, assessment of Week 48 data may further elucidate potential predictors of MDA after longer-term treatment.References[1]Coates C et al. Ann Rheum Dis 2021; 0: 1–11.Disclosure of InterestsWilliam Tillett Speakers bureau:, Consultant of:, Grant/research support from: William Tillett has received research grants and consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB., Sarah Ohrndorf Speakers bureau: Sarah Ohrndorf has received speaker fees or travel expense reimbursements from AbbVie, BMS, Janssen, Novartis and Pfizer., Julio Ramírez Speakers bureau:, Consultant of: Julio Ramírez has received consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis and UCB., Marlies Neuhold Shareholder of: Johnson & Johnson., Employee of: Janssen, Robert Wapenaar Shareholder of: Johnson & Johnson., Employee of: Janssen, Elke Theander Shareholder of: Johnson & Johnson., Employee of: Janssen, Christine CONTRE Shareholder of: Johnson & Johnson., Employee of: Janssen, Mohamed Sharaf Shareholder of: Johnson & Johnson., Employee of: Janssen, May Shawi Shareholder of: Johnson & Johnson., Employee of: Janssen, Marijn Vis Speakers bureau:, Consultant of:, Grant/research support from: Marijn Vis has received research grants and consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation.