European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.

BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.

Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies.

Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and non-targeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly non-committing discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker-drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed.

Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor alpha inhibitor. METHODS: Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks' follow-up. The patient's assessment of arthritis pain (pain), patient's assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded. RESULTS: At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (> or =0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components. CONCLUSIONS: CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis.

OBJECTIVES: To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis. METHODS: Patients with recent-onset rheumatoid arthritis receiving traditional antirheumatic therapy from either the BeSt study, a randomised controlled trial comparing different treatment strategies (group A), or two Early Arthritis Clinics (group B) were included. In group A, systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS < or =2.4). In group B, treatment was left to the discretion of the treating doctor. Functional ability (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated. RESULTS: At baseline, patients in group A (n = 234) and group B (n = 201) had comparable demographic characteristics and a mean HAQ of 1.4. Group A had a longer median disease duration than group B (0.5 vs 0.4 years, p = 0.016), a higher mean DAS28 (6.1 vs 5.7, p<0.001), more rheumatoid factor-positive patients (66% vs 42%, p<0.001) and more patients with erosions (71% vs 53%, p<0.001). After 1 year, the HAQ improvement was 0.7 vs 0.5 (p = 0.029), and the percentage in remission (DAS28 <2.6) 31% vs 18% (p<0.005) in groups A and B, respectively. In group A, the median SHS progression was 2.0 (expected progression 7.0), in group B, the SHS progression was 1.0 (expected progression 4.4). CONCLUSIONS: In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression.

Efficacy of intraarticular infliximab in patients with chronic or recurrent gonarthritis: a clinical randomized trial.

OBJECTIVE: To evaluate the efficacy and safety of intraarticular infliximab compared with intraarticular methylprednisolone in patients with gonarthritis. METHODS: In 23 patients with recurrent gonarthritis despite previous intraarticular corticosteroid therapy, a total of 41 intraarticular injections (20 infliximab and 21 methylprednisolone) were performed in 28 knees. Initial therapy was randomly assigned, and crossover therapy was eligible within 3 months. The clinical effect was assessed during 6 months of followup. The primary outcome was event-free survival, defined as the time after treatment until local retreatment was performed and/or nonimprovement of the knee joint score. Adverse effects were recorded during followup. RESULTS: All patients treated with intraarticular infliximab had an insufficient response. In contrast, 8 of the 21 intraarticular methylprednisolone injections were effective (P = 0.004). Between groups, no differences in the patients' age, disease duration, number of disease-modifying antirheumatic drugs, or previous intraarticular methylprednisolone were observed. Reported adverse effects were not related to therapy. CONCLUSION: Treatment with intraarticular infliximab injection was not effective in patients with a chronically inflamed knee joint. Intraarticular injection with methylprednisolone was superior despite previous intraarticular corticosteroid therapy. Further investigation is needed to provide these patients with a better alternative.

Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment.

OBJECTIVE: Joint damage is related to disease activity in rheumatoid arthritis (RA), but the degree of its progression and the temporal associations between disease activity and joint damage are unclear. The aim of this study was to evaluate whether there is a latency in the effect of disease activity on radiographic progression in patients with RA. METHODS: Data were obtained from the PREMIER trial, a 2-year randomized, controlled clinical trial of adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in early RA. Radiographic progression of joint damage was calculated using the modified total Sharp score in a subset of patients whose disease was in remission (Simplified Disease Activity Index

Patient-reported outcomes in a randomized trial comparing four different treatment strategies in recent-onset rheumatoid arthritis.

OBJECTIVE: To investigate the effectiveness of 4 different treatment strategies for recent-onset rheumatoid arthritis (RA) on 2-year patient-reported outcomes, including functioning and quality of life. METHODS: A total of 508 patients with recent-onset RA were randomly assigned to 1) sequential monotherapy, 2) step-up combination therapy, both starting with methotrexate, 3) initial combination therapy, including a tapered high-dose prednisone, or 4) initial combination therapy with methotrexate and infliximab. Treatment was adjusted every 3 months if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis Patient Preference Disability Questionnaire, the Short Form 36 (SF-36), and scores for pain, global health, and disease activity measured on a 100-mm visual analog scale (VAS) were compared between groups at baseline and every 3 months thereafter for 2 years. RESULTS: After 2 years, all patient-reported outcomes had improved significantly from baseline, irrespective of the treatment strategy. SF-36 subscale scores approached population norms for 3 physical components, and achieved population norms (P > 0.05) for bodily pain and 4 mental components. Improvement in functioning, VAS scores, and physical items of the SF-36 occurred significantly earlier in patients treated with initial combination therapies (all comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus groups 3 and 4). CONCLUSION: All 4 DAS-driven treatment strategies resulted in substantial improvements in functional ability, quality of life, and self-assessed VAS scores after 2 years. Initial combination therapy led to significantly faster improvement in all patient-reported measures.

Safety of biological therapies following rituximab treatment in rheumatoid arthritis patients.

OBJECTIVE: To assess the safety of biological disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients following rituximab. METHODS: RA patients who participated in an international rituximab clinical trial programme were included. Patients who had received one or more rituximab courses and entered safety follow-up (SFU) were permitted additional biological DMARD. Serious infection events (SIE) were collected. RESULTS: Of 185 of 2578 patients who entered SFU and received another biological DMARD, 88.6% had peripheral B-cell depletion at the time of initiation of another biological agent. Thirteen SIE (6.99 events/100 patient-years) occurred following rituximab but before another biological DMARD and 10 SIE (5.49 events/100 patient-years) occurred following another biological DMARD. SIE were of typical type and severity for RA patients. 153 had received one or more tumour necrosis factor inhibitor(s). No fatal or opportunistic infections occurred. CONCLUSIONS: In this analysis, treatment with biological DMARD after rituximab was not associated with an increased serious infection rate. Sample size with limited follow-up restricts definitive conclusions.

Progression of hand osteoarthritis over 2 years: a clinical and radiological follow-up study.

OBJECTIVES: To investigate the course of hand osteoarthritis over 2 years by currently available outcome measures. METHODS: 189 participants of the Genetics, Arthrosis and Progression (GARP) study with hand osteoarthritis were followed for 2 years. Self-reported hand pain and functional limitations were assessed with the Australian/Canadian osteoarthritis hand index (AUSCAN LK 3.0). Pain intensity upon lateral pressure in the interphalangeal and thumb base joints was graded on a four-point scale. Osteophytes (0-3) and joint space narrowing (JSN) (0-3) was scored at baseline and after 2 years in interphalangeal and thumb base joints. Standardised response means (SRM) were calculated. RESULTS: 172 (91%) patients completed the 2-year follow-up (mean age 60.5 years, 78.5% women). Statistically significant increases in self-reported pain and function scores, in pain intensity scores as well as in osteophyte and JSN total scores were seen over 2 years. SRM were 0.25, 0.23, 0.67, 0.34 and 0.35, respectively, for self-reported pain and function scores, pain intensity scores, osteophyte and JSN total scores. Radiological progression was not associated with changes in self-reported pain and function. Women in an early post-menopausal stage were especially at risk of progressing radiologically. CONCLUSIONS: Currently available outcome measures were able to assess progression over the relatively short time period of 2 years. Radiographic outcomes were more responsive than self-reported outcomes. Pain intensity upon lateral pressure seems to be a responsive measure but needs validation.

Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis.

OBJECTIVES: To compare the clinical and radiological efficacy of initial vs delayed treatment with methotrexate (MTX) and infliximab (IFX) in patients with recent onset rheumatoid arthritis (RA). METHODS: In a post hoc analysis of the BeSt study (for Behandel Stratagieen, Dutch for treatment strategies), 117 patients who started initial MTX+IFX were compared with 67 patients who started MTX+IFX treatment after failing (disease activity score (DAS)>2.4; median delay to IFX: 13 months) on > or =3 traditional DMARDs. If the DAS remained >2.4, the protocol dictated IFX dose increases to 6, 7.5 and 10 mg/kg. In case of a DAS < or =2.4 for > or =6 months, IFX was tapered and finally stopped. We aimed to correct for allocation bias using propensity scores. Functional ability was measured by the Health Assessment Questionnaire (HAQ), radiological progression by Sharp/van der Heijde scoring (SHS). RESULTS: Baseline differences between the initial and delayed groups were no longer significant after propensity score adjustment. At 3 years after baseline, patients treated with initial MTX+IFX experienced more improvement in HAQ over time and were less likely to have SHS progression than patients treated with delayed MTX+IFX (p = 0.034). At 2 years after IFX initiation, more patients in the initial group compared with the delayed group could discontinue IFX after a good response (56% vs 29%, p = 0.008). CONCLUSIONS: The results of this post hoc analysis suggest that using MTX+IFX as initial treatment for patients with recent onset RA is more effective than reserving MTX+IFX for patients who failed on traditional DMARDs, with more HAQ improvement over time, more IFX discontinuation and less progression of joint damage.