Long-term costs and outcomes in psoriatic arthritis patients not responding to conventional therapy treated with tumour necrosis factor inhibitors: the extension of the Psoriatic Arthritis Cost Evaluation (PACE) study.

OBJECTIVES: Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs). METHODS: Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared. RESULTS: The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years. CONCLUSIONS: The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.

The adherence to ASAS classification criteria and to ASAS recommendations for the use of anti-TNH-alpha agents in axial spondyloarthritis.

OBJECTIVES: To determine the adherence of practicing rheumatologists, before and after an educational project, to Assessment of SpondyloArthritis international Society (ASAS) classification criteria and to ASAS recommendations for the use of anti-tumor necrosis factor (TNF)-alpha agents in patients with axial spondyloarthritis (SpA). METHODS: The project involved 53 rheumatologists attending 2 educational meetings on an update of SpA. Each meeting included interactive sessions on 1) clinical cases, 2) clinimetric evaluation, including ASAS core set for daily practice and 3) imaging. Diagnostic and therapeutic approach of each participant was tested using short clinical cases, obtained from real-life rheumatology settings, at the beginning and at the end of this educational project. Each case for diagnostic (n=10) or therapeutic purpose (n=10) had 10 possible choices. Each participant gave a score from 0 (total disagreement) to 10 (total agreement) for each choice. RESULTS: At baseline, the rheumatologists had an excellent agreement with ASAS classification criteria for axial SpA and anti-TNF-alpha treatment according to ASAS recommendations with a further significant improvement after the educational programme. In axial SpA cases with acute anterior uveitis (AU) or Crohn's disease, anti-TNF-alpha treatment was indicated mainly as monoclonal anti-TNF antibody. In presence of elevated levels of CRP, anti-TNF option has been considered useful. CONCLUSIONS: Practicing rheumatologists had a satisfying adherence to ASAS classification criteria and to ASAS recommendations for the use of anti-TNF-alpha agents for patients with axial SpA. Extra-articular manifestations and other variables might play a role in the decision-process of the management of axial SpA.

Pharmacoeconomic burden in the treatment of psoriatic arthritis: from systematic reviews to real clinical practice studies.

The economic assessment of treatment options in a chronic and severe disease like Psoriatic Arthritis (PsA) is crucial to estimate the burden of costs. In particular, the impact of new costly medications such as biologic agents have been studied to figure this important aspect of a multifaceted disease. In a previous observational, longitudinal multicentre cost evaluation study, the results showed that biologic agents are cost-effective. This study was obtained from the real clinical practice and encompassed PsA patients refractory to traditional treatments. Similar data were also obtained from reviews analysis of Randomized Controlled Trials (RCTs). Recently, Cawson et al. performed a systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active PsA. The review was conducted to identify relevant, recently published studies and the new trial data were synthesized, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). In particular the analysis showed that, on average, etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. This study, as a systematic review, has been focused on main RCTs on active PsA treated by biological DMARDs and limitations to this analysis arise from a paucity of data on long-term follow up, as well as radiological progression and long-term safety. These interesting results reflected the important role of biologic agents in the management of PsA, highlighting their efficacy and cost-effectiveness. However, there are some unmet needs for pharmacoeconomic considerations based on prospective and/or on real clinical practice studies, as well as considering all the intriguing aspects of this challenging disease.

Remission in ankylosing spondylitis treated with anti-TNF-α drugs: a national multicentre study.

OBJECTIVE: The primary objective of this retrospective study was to investigate the possibility of achieving partial remission (PR) in AS patients treated with anti-TNF-α antagonists, such as adalimumab (ADA), etanercept (ETA) and infliximab (INF), in a real clinical practice setting. Predictors of PR were also evaluated. METHODS: A retrospective study was conducted in patients with AS treated with ADA, ETA and INF from 2000 to 2012. Kaplan-Meier survival curves were plotted to determine the rates of PR during the treatment with anti-TNF-α drugs. RESULTS: A total of 283 patients with AS were treated with ADA (18.7%), ETA (26.8%) and INF (54.4%) as first anti-TNF-α drugs, with a PR rate of 57.6%. The probability of obtaining PR with ADA, ETA or INF was not significantly different among all anti-TNF-α patients. AS patients treated with a second anti-TNF-α drug had a PR rate of 40.5%, but after switching for lack of response, the probability of obtaining PR with a second anti-TNF-α drug was significantly lower from that of the first anti-TNF-α drug (P = 0.0039). The probability of obtaining PR in patients with enthesitis (P = 0.04) or psoriasis (P = 0.0016) or low levels of CRP (P = 0.0225) was significantly lower compared with that of patients without these manifestations at baseline. CONCLUSION: Our real-life study on PR confirmed the effectiveness of ADA, ETA or INF as first or second anti-TNF-α drugs. The presence at baseline of enthesitis or psoriasis or low CRP values yielded a lower probability of obtaining PR.

Unmet needs in outcome measures of Psoriatic Arthritis: focus on axial radiographic and nail involvement.

OBJECTIVES: This article reviews some unmet needs on the outcome measures in Psoriatic Arthritis (PsA). In particular, the radiological assessment of axial PsA and the assessment of nail involvement still remain problematic and this, in turn, could affect the best management. At present, the radiological assessment of spine has been evaluated by using scoring systems borrowed from Ankylosing Spondylitis (AS). In particular, the Bath Ankylosing Spondylitis Radiology Index (BASRI) and the modified Stoke Ankylosing Spondylitis Spine Score (m-SASSS) have been validated for the axial PsA and a new index for assessing the radiological axial involvement in PsA was also developed, called Psoriatic Arthritis Spondylitis Radiology Index (PASRI). Nail involvement has been evaluated by two different instruments: the Nail Psoriasis Severity Index (NAPSI) and its modified version (mNAPSI). Both are good instruments but only a few data are available on these instruments when adopted at a daily clinical practice level.

Biomarkers of subclinical atherosclerosis in patients with autoimmune disorders.

Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, and ß-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of ß-carotene in patients with RA and PsA than in controls. ß-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders.

Etanercept in psoriatic arthritis.

In this update on etanercept (ETN) in psoriatic arthritis (PsA) we analyze this drug's mechanism of action, clinical efficacy/effectiveness, optimal dosage, disease-modifying antirheumatic drugs (DMARD) association, radiological progression, safety, switching aspects, and pharmacoeconomy. The efficacy/effectiveness of ETN in PsA has been demonstrated in randomized placebo-controlled trials as well as in observational studies representing routine clinical practice. At 1 and 2 years, ETN inhibited radiographic disease progression, assessed by the modified total Sharp score. ETN (generally at a dosage of 50 mg/weekly) can be used either in monotherapy or in combination with DMARD such as methotrexate. A systematic search of randomized, placebo-controlled trials of ETN to treat adults with plaque psoriasis or PsA suggests that the short-term risk/benefit ratio is favorable. Longterm studies, such as observational studies, confirmed this safety profile of ETN. A variable percentage of patients withdrew anti-tumor necrosis factor-α (TNF-α) inhibitor treatment owing to inefficacy or poor tolerability. Observational studies showed that in the case of treatment failure with 1 agent, switching to the other agent may also be useful in patients with PsA because of the different molecular structures and targets of available TNF-α blockers. The clinical effect of ETN is associated with favorable pharmacoeconomic considerations.

The radiological assessment of axial involvement in psoriatic arthritis.

This article summarizes the state of radiological assessment of axial involvement in psoriatic arthritis (PsA). The definition and measurement of axial disease in PsA remain problematic and this situation in turn could affect the choice of approach to evaluate radiological findings of the spine. At present, the radiological assessment has been evaluated by using scoring systems borrowed from ankylosing spondylitis (AS). In particular, the Bath AS Radiology Index (BASRI) and the modified Stoke AS Spine Score (m-SASSS) have been validated for axial PsA. A recent study showed that BASRI and m-SASSS were valid instruments; however, neither score encompassed all radiological features of PsA. Therefore, a new index for assessing radiological axial involvement in PsA was developed--the PsA Spondylitis Radiology Index (PASRI). This new index encompassed a greater range of the spinal radiological features of PsA, providing a greater score range, and it correlated well with anthropometric and patient-reported outcomes. Recently, a study assessed the sensitivity to change of BASRI, m-SASSS, and PASRI, and showed that these 3 instruments provided a moderate sensitivity to change but high specificity to detect the true changes.

Clinical and ultrasonography assessment of peripheral enthesitis in ankylosing spondylitis.

OBJECTIVE: The aim of this study was to compare clinical examination with power Doppler US (PDUS) in the detection of entheseal abnormalities in patients with AS. METHODS: Thirty-six AS patients underwent clinical and PDUS examination of the following bilateral entheseal sites: common extensor tendon at its insertion at the lateral humeral epicondyle; gluteus tendons at their insertion at the greater trochanter; quadriceps tendon at its insertion at the superior pole of the patella; patellar tendon at its proximal insertion at the inferior pole of the patella; patellar tendon at its distal insertion at the tibial tuberosity; Achilles tendon at its insertion at the calcaneus; and plantar aponeuroses at its insertion at the calcaneus. RESULTS: Clinical and PDUS examination revealed at least one abnormal enthesis in 23 (63.9%) and 35 (97.2%) AS patients, respectively. Furthermore, of 432 entheses examined in our 36 AS patients, 64 (14.8%) were considered abnormal by clinical examination and 192 (44.4%) by PDUS. US abnormalities most commonly found were enthesophytes (31.7%), calcifications (33.7%), thickening (29.8%) and hypoechogenicity (26.6%). We found erosions and PD signals in 9.7 and 6% of examined entheseal sites, respectively. The evidence of entheseal abnormalities by clinical examination has a poor likelihood ratio (LR) for the presence of US abnormalities with vascularization (LR = 1.61), without vascularization (LR = 1.24) or erosions (LR = 1.51) at all sites. CONCLUSIONS: PDUS permits detection of structural and inflammatory abnormalities of the enthesis in AS and may complement the physical examination in order to better evaluate enthesitis.

Rituximab infusion-related adverse event rates are lower in patients with systemic lupus erythematosus than in those with rheumatoid arthritis.

OBJECTIVES: Rituximab (RTX) is a therapeutic option for patients with SLE or RA. We conducted a prospective, longitudinal, observational study to compare rates of RTX-related adverse events (AEs) in these two patient groups. METHODS: RTX was used in 23 patients with SLE that was refractory to conventional therapy and in 31 patients with RA that had been unsuccessfully treated with TNF-α inhibitors. Infusion-related and infectious AE rates were calculated for each group. RESULTS: Seven (22.5%) RA patients experienced an infusion-related reaction. These AEs involved 7/91 (7.7%) infusions administered in the RA group. None of the 102 infusions administered to SLE patients was associated with infusion-related AEs (P = 0.038 vs RA group). The mean daily glucocorticoid dose administered during the week preceding RTX treatment in the SLE group was higher than that for the RA group [0.25 (0.2) vs 0.18 (0.14) mg/kg, P = not significant] and significantly higher than that received by the subgroup of the seven RA patients who experienced infusion-related AEs [0.10 (0.02) mg/kg; P = 0.0017]. Infectious AE rates were also lower (but not significantly so) in the SLE group (8.7 vs 12.9% in RA). CONCLUSIONS: Repeated cycles of RTX in combination with different immunosuppressants is a safe therapeutic option for SLE and RA patients. The lower incidence of infusion-related AEs in the SLE patients might reflect the higher dosage glucocorticoid therapy they received during the week before RTX infusion.