Serum adenosine deaminase may predict disease activity in rheumatoid arthritis

To determine the relationship between serum adenosine deaminase (ADA) and disease activity, and to develop a new disease activity index based on serum ADA in rheumatoid arthritis (RA). Seventy RA patients were included. Disease activity based on Disease Activity Score 28-ESR (DAS28-ESR) and Disease Activity Score 28-CRP (DAS28-CRP) and serum ADA were measured. There were correlations when serum ADA compared with DAS28-ESR and DAS28-CRP. (R ²?=?0.014, 0.175, respectively, P values?<?0.00). New disease activity index was developed by replacing ADA with ESR and CRP in DAS28-ESR and DAS28-CRP. There were strong correlations when new model compared with DAS28-ESR and DAS28-CRP. (R ²?=?0.94 and 0.95, respectively, P values?<?0.00) The best new model values corresponding to DAS28-ESR values of 2.6, 3.2, and 5.1 were 2.79, 3.4, and 4.82, respectively; and new model values corresponding to DAS28-CRP values of 2.3, 2.7, and 4.1 were 2.1, 2.9, and 4, respectively. There were agreements when the new model compared with DAS28-ESR and DAS28-CRP for determination of patients in different disease activity categories. (Kappa?=?0.81 and 0.71, respectively, P values?<?0.00). The new disease activity index that applies serum ADA may help in predicting disease activity in RA.     

IL-6 is an independent predictive factor of drug survival after dose escalation of infliximab in patients with rheumatoid arthritis

Objective: We aimed to investigate factors predictive of increased serum infliximab (IFX) concentration with improvement of disease activity, as well as better 1-year continuation rate after dose escalation, in patients with rheumatoid arthritis (RA) who showed inadequate response to 3?mg/kg IFX.

Methods: Among 42 patients allotted to receive 3?mg/kg IFX, 13 patients showed adequate response (DAS28?Results: One year after IFX dose escalation, 25 patients completed the study protocol, and 16 patients (64%) continued to show a good response for one year, while 9 patients (36%) required switching of biologics because of inadequate response. Multivariate analyses revealed that a serum IL-6 level of less than 4.0?pg/mL at baseline was the only factor predictive of a clinically beneficial increase of serum IFX concentration in patients who required dose escalation. Receiver operating characteristic analysis revealed that 5.16?pg/mL of IL-6 was the cut-off value with sensitivity 0.833 and specificity of 0.769 (95%CI for AUC: 0.712–1.006). In patients with IL-6 levels of less than 5.16?pg/mL at baseline, the serum IFX concentration significantly increased after dose escalation with adequate response. The 1-year drug survival rates of patients with IL-6 levels less than 5.16?pg/mL and in those with levels greater than or equal to 5.16?pg/mL at baseline were 83.3% and 30.8%, respectively (log-rank test, p?=?.011).

Conclusions: The results of our study indicated that a baseline serum level of IL-6 below 5.16?pg/mL might be a predictive factor for a clinically beneficial increase of serum IFX concentration with improvement of disease activity and better 1-year continuation rate after IFX dose escalation.     

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab

Objective: This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA).

Methods: Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP)?Results: DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382–0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002–1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively.

Conclusion: Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.     

Time lag between the initiation of adalimumab after methotrexate correlates with the efficacy of adalimumab in rheumatoid arthritis patients

Objectives: To evaluate the efficacy and safety of adalimumab (ADA) and methotrexate (MTX) in patients with rheumatoid arthritis (RA) and investigate critical factors associated with efficacy.

Methods: In this retrospective cohort study, patients received ADA at a single facility. Clinical outcome was retrospectively evaluated using the Disease Activity Score in 28 joints with Erythrocyte Sedimentation Rate (DAS28-ESR).

Results: Of the 122 patients undergoing treatment with ADA between July 2008 and April 2014, DAS28-ESR data after 6 months of treatment were available for 103 and 87 (84.5%) were treated with a combination of ADA and MTX. For combination therapy, time lag between MTX and the initiation of ADA significantly correlated with efficacy of ADA at 6 months, as well as prior use of biologics, but not disease duration.

Conclusions: Clinical outcomes were correlated with the time lag between MTX and the initiation of ADA, not disease duration. Early initiation of ADA after MTX might improve clinical outcomes.     

Gender specific differences in patients with psoriatic arthritis

Objectives: To assess gender related differences in a cohort of patients with psoriatic arthritis (PsA).

Methods: Consecutively recruited patients were included and underwent clinical, radiological and laboratory evaluation by using standardized protocol and case report forms.

Results: Women (n?=?115) with PsA had higher symptom duration and body mass index (BMI), tender and swollen joint counts, disease activity score-28 joints (DAS28), Erythrocyte sedimentation rate (ESR) and poorer physical activity and fatigue than men (n?=?72) with PsA. Psoriasis area and severity index (PASI) were higher in male patients. However quality of life (SF36 physical and mental component scores), articular pattern, extra-articular features (including uveitis, iritis) and family history for psoriasis, spondyloarthritis (SpA) (PsA and ankylosing spondylitis [AS]) were quite similar between men and women.

Conclusions: Some of the clinical and laboratory variables tend to be different between men and women with PsA. The extent of quality of life and articular pattern seem to be similar in both genders. Men with PsA are more likely to have higher PASI scores and longer duration to develop arthritis after the onset of psoriasis, while women are more likely to have higher disease activity and report more fatigue and physical activity limitations.     

Safety and effectiveness of abatacept in Japanese non-elderly and elderly patients with rheumatoid arthritis in an all-cases post-marketing surveillance

Abstract

Objectives: To investigate the safety, effectiveness, and risk-benefit balance of intravenous abatacept (ABA) in non-elderly (<65 years: NEG) and elderly (≥65 years: EG) rheumatoid arthritis patients.

Methods: This sub-analysis of an all-cases postmarketing surveillance in Japan assessed safety in all enrolled patients and effectiveness in those with Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) measurements at ≥2 time points including baseline. Risk-benefit was evaluated based on infections and DAS28-CRP improvement >1.2.

Results: The NEG and EG of the safety analysis set comprised 2,170 and 1,712 patients, respectively; corresponding 6-month ABA retention rates were 80.2% and 77.1%. The NEG had fewer adverse drug reactions (14.5% vs. 17.2%, p?=?.021) and infections (4.8% vs. 7.2%, p?=?.002) than the EG. DAS28-CRP changed similarly between groups. The proportion of patients with low-risk/high-benefit and high-risk/low-benefit were 33.1% and 6.9% (NEG) and 29.7% and 9.0% (EG). Low-risk/high-benefit patients were younger, had shorter disease duration and fewer comorbidities, and were with less use of oral glucocorticoid and prior biologics, more use of methotrexate and higher DAS28-CRP than high-risk/low-benefit patients at baseline.

Conclusion: ABA was well tolerated and similarly efficacious in the EG and NEG. Identification of factors related to low-risk/high-benefit may aid appropriate patient selection.     

Addition of another disease-modifying anti-rheumatic drug to methotrexate reduces the flare rate within 2 years after infliximab discontinuation in patients with rheumatoid arthritis: An open,randomized, controlled trial

Abstract

Objectives. We examined whether the addition of another conventional disease-modifying anti-rheumatic drugs (DMARDs) to methotrexate (MTX) upon infliximab (IFX) discontinuation in well-controlled rheumatoid arthritis (RA) patients could suppress subsequent disease flare.

Methods. RA patients maintaining DAS28-CRP (Disease Activity Score of 28 joints with C-reactive protein) scores < 2.6 for ≥ 6 months with IFX were randomized either to receive addition of bucillamine (BUC) to MTX (BUC + MTX group; n = 24) or not (MTX group; n = 31) upon discontinuing IFX. The primary endpoint was the flare rate within 2 years of IFX discontinuation.

Results. Six patients discontinuing MTX during the study were excluded from analyses. Seventeen patients (63.0%) experienced flares in the MTX group, which was significantly reduced in the BUC + MTX group (31.8%; p = 0.045). Further, the flare rates differed significantly between remission and non-remission by a Boolean definition upon IFX discontinuation in the MTX group (40.0% vs. 91.7%, respectively; p = 0.014), but they were comparable in the BUC + MTX group. BUC treatment was interrupted in seven patients due to rash, proteinuria and incompliance.

Conclusions. DMARDs combination therapy may be a better treatment strategy than MTX monotherapy for maintaining RA control after successful discontinuation of biological agents.     

Fractures lead to worsening of disease activity in rheumatoid arthritis

Objectives: The cause of rheumatoid arthritis (RA) flares is multifactorial and not well understood. No reports of fractures influencing disease activity in patients with RA have been published. The purpose of this study was to determine whether fractures influence disease activity in patients with RA.

Methods: Hospital records of 470 patients with RA between 2011 and 2014 were analyzed. We first examined the incidence of flare using multiple regression analysis. Secondly, we examined the incidence of flare using DAS28-ESR, DAS28-CRP, and drug changes before bone fracture until bone union in the fracture cases.

Results: Multiple linear regression analysis showed that female sex (p?<?0.001), bottom DAS28-ESR (p?<?0.001), and fracture (p?=?0.041) were independent factor for DAS28-ESR at the last observation period, and sex (p?=?0.040), bottom DAS28-CRP (p?<?0.001), and fracture (p?=?0.019) were independent factor for DAS28-CRP at the last observation period. The average DAS28-ESR value was significantly increased from 3.19 (prefracture) to 3.58 (bone union). The average DAS28-CRP value was also significantly increased from 2.45 (prefracture) to 2.79 (bone union).

Conclusions: We have demonstrated that fractures influence disease activity in patients with RA. Larger numbers of fracture cases are required to confirm the present observations; however, the prevention of fracture is clearly required in patients with RA.     

Development of psoriasis in IBD patients under TNF-antagonist therapy is associated neither with anti-TNF-antagonist antibodies nor trough levels

Background: The cause of anti-TNF-induced psoriasis is still unknown.

Objective: We aimed to evaluate if the appearance of psoriasis under anti-TNF therapy is associated with anti-TNF antibody levels and TNF-antagonist trough levels.

Methods: In this case-control study we identified 23 patients (21 with Crohn’s disease [CD], two with ulcerative colitis [UC]) who developed psoriasis under infliximab (IFX, n?=?20), adalimumab (ADA, n?=?2), and certolizumab pegol (CZP, n=?1) and compared them regarding the anti-TNF-antagonist antibody levels with 85 IBD patients (72 with CD, 13 with UC) on anti-TNF therapy without psoriasis.

Results: Median disease duration was not different between the two groups (7 years in the group with psoriasis under TNF-antagonists vs. 10 years in the control group, p?=?0.072). No patient from the psoriasis group had antibodies against TNF-antagonists compared to 10.6% in the control group (p?=?0.103). No difference was found in IFX trough levels in the group of patients with psoriasis compared to the control group (2.6?μg/mL [IQR 0.9–5.5] vs. 3.4?μg/mL [IQR 1.4–8.1], p?=?0.573). TNF-antagonist therapy could be continued in 91.3% of patients with TNF-antagonist related psoriasis and most patients responded to topical therapies.

Conclusion: Anti-TNF-induced psoriasis seems to be independent of anti-TNF antibodies and trough levels. Interruption of Anti-TNF therapy is rarely necessary.     

Association of anti-Ro/SSA antibody with response to biologics in patients with rheumatoid arthritis

Objective: To compare the effectiveness of three different biologics in anti-Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA).

Methods: The study subjects were 110 biologics naïve patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody-negative patients.

Results: We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-β levels.

Conclusions: Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-β levels, but not to TCZ and ABT.     

Drug levels, anti-drug antibodies, and clinical efficacy of the anti-TNFα biologics in rheumatic diseases

The objectives of this study are to evaluate the effect of anti-drug antibodies on the clinical efficacy and withdrawal rate of the anti-TNFα biologics in patients with rheumatic diseases. Consecutive patients with rheumatic diseases recently commenced on anti-TNFα biologics were recruited. Serum samples were collected for assay of drug level and antibody titer against the corresponding biologics. Comparison of the clinical efficacy and drug retention rate was performed between patients with and without anti-drug antibodies. Fifty-eight Chinese patients were studied (64 % women; age 47.8?±?12.9 years; disease duration 6.7?±?6.4 years). The proportion of patients using infliximab (IFX), adalimumab (ADA), and etanercept (ETN) was 41, 28, and 31 %, respectively. Antibodies against IFX, ADA, and ETN were demonstrated in 12(50 %), 5(31 %) and 0(0 %) patients, respectively. Patients who developed anti-drug antibodies had significantly lower levels of the corresponding drugs (IFX level: 0.004?±?0.01 vs 3.81?±?3.49 μg/ml; p?=?0.002; ADA level: 0.0 vs 7.6?±?8.3 μg/ml; p?=?0.008). Anti-drug antibody-positive patients had a significantly higher cumulative drug withdrawal rate due to inefficacy (64.7 and 71.8 % vs 10.3 and 10.3 % at month 12 and month 24, respectively; p?<?0.001). In rheumatoid arthritis and psoriatic arthritis, non-responders was significantly more frequent in antibody-positive patients (54 vs 13 %; p?=?0.01). In spondyloarthritis, the improvement in ankylosing spondylitis disease activity score was significant in patients without antibodies (3.89?±?0.82 to 2.22?±?0.86; p?=?0.01) but not in those with anti-drug antibodies (3.40?±?1.67 to 3.23?±?1.40; p?=?0.73). We concluded that the presence of neutralizing antibodies is associated with lower serum levels of the anti-TNFα biologics, leading to lower efficacy and higher withdrawal rate.     

Comparison of Long-term Outcomes of Infliximab versus Adalimumab in 1,488 Biologic-Naive Korean Patients with Crohn’s Disease

Background/AimsData on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with Crohn’s disease (CD) are rare, particularly for Asian patients. We compared the key clinical outcomes (surgery, hospitalization, and corticosteroid use) of use of these two drugs in biologic-naive Korean patients with CD.MethodsUsing National Health Insurance claims, we collected data on patients who were diagnosed with CD and exposed to IFX or ADA between 2010 and 2016.ResultsWe included 1,488 new users of biologics (1,000 IFX users and 488 ADA users). Over a median follow-up period of 2.1 years after starting biological therapy, no significant differences were found between IFX and ADA users in the risks for surgery (ADA vs IFX adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.81 to 1.84), hospitalization (aHR, 1.02; 95% CI, 0.81 to 1.28), and corticosteroid use (aHR, 0.82; 95% CI, 0.56 to 1.19). These results were unchanged even when only patients who used biologics for over 6 months were analyzed (aHR [95% CI] surgery, 1.31 [0.82 to 2.11]; hospitalization, 1.02 [0.80 to 1.30]; corticosteroid use, 0.80 [0.54 to 1.18]). Additionally, these results were unchanged in patients treated with biologics as monotherapy or in combination with immunomodulators.ConclusionsIn this nationwide population-based study, no significant difference was found in the long-term effectiveness of IFX and ADA in the real-world setting of biologic-naive Korean patients with CD. In the absence of trials to directly compare IFX and ADA, our study indicates that the selection of one of these two biologics can be determined by patient and/or physician preference.     

Reduction of methotrexate and glucocorticoids use after the introduction of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis in daily practice based on the IORRA cohort

Objectives: To evaluate usage patterns for methotrexate (MTX) and/or glucocorticoids in rheumatoid arthritis (RA) patients receiving biological disease-modifying antirheumatic drugs (bDMARDs) in daily practice.

Methods: Data from RA patients who commenced treatment with bDMARDs (infliximab [IFX], etanercept [ETN], tocilizumab [TCZ], or adalimumab [ADA]) from 2008 to 2010 were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The proportions of patients taking concomitant MTX and glucocorticoids and doses of these medications were evaluated before and 2 years after initiation of each bDMARD.

Results: A total of 470 RA patients who had initiated a bDMARD (IFX: n?=?98, ETN: n?=?181, TCZ: n?=?90, and ADA: n?=?101) were evaluated. The proportion of patients taking MTX decreased over time among ETN and TCZ users, while it increased among ADA users. The MTX dose decreased over time among IFX, ETN, and TCZ users, but not among ADA users. Although the rate of glucocorticoid use and dose decreased after bDMARD initiation in all four bDMARD groups, approximately 50% of patients continued to receive glucocorticoids 2 years after bDMARD initiation.

Conclusion: MTX and glucocorticoid use and doses in daily practice were commonly reduced after the initiation of bDMARDs, with the dose adjustment varied depending on the bDMARD.     

The efficacy of abatacept in Japanese patients with rheumatoid arthritis: 104 weeks radiographic and clinical results in clinical practice

Objective: We aimed to assess the efficacy of abatacept in Japanese patients with rheumatoid arthritis (RA) in clinical practice.

Methods: We examined 92 patients who received abatacept for 104 weeks. Analysis of radiographic efficacy was conducted using van der Heijde-modified total Sharp score (mTSS). Disease activity score was assessed using disease activity score in 28 joints (DAS28) and simplified disease activity index (SDAI) by last observation carried forward.

Results: The change in mTSS was 0.61 at 52 weeks and 0.27 at 52–104 weeks. Structural remission occurred in 64.9% at 52 weeks and 76.6% at 104 weeks. The significant risk factors for joint damage progression at 52 weeks were prednisolone use, baseline C-reactive protein level (CRP), and erythrocyte sedimentation rate (ESR), as well as average DAS28-CRP and DAS28-ESR scores, SDAI, CRP, ESR, and matrix metalloproteinase-3 (MMP-3) levels. The clinical remission rates were 47.8% by DAS28-CRP, 39.1% by DAS28-ESR, and 30.4% by SDAI at 52 weeks, were 59.8% by DAS28-CRP, 48.9% by DAS28-ESR, and 43.5% by SDAI at 104 weeks.

Conclusion: This study suggested efficacy of abatacept treatment in Japanese patient with RA for 104 weeks in daily clinical practice. Abatacept lead to suppress joint destruction for 104 weeks.     

Minimum Effective Dosages of Anti-TNF in Rheumatoid Arthritis: A Cross-sectional Study

AimsTo evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR.Patients and methodsCross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. Main variables: dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR.Results195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%).ConclusionsRA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients.     

Twenty-four-week clinical results of adalimumab therapy in Japanese patients with rheumatoid arthritis: retrospective analysis for the best use of adalimumab in daily practice

Abstract

Objective We evaluated patient drug adherence to and efficacy and safety of adalimumab (ADA) based on data collected from approximately 200 patients to retrospectively examine the best use of ADA in Japanese patients with longstanding rheumatoid arthritis (RA) managed in daily practice.

Methods For explorative comparisons, patients were stratified by prior use or no use of biologics (Bio-naïve vs. Bio-switch) and concomitant use (+) or no use (?) of methotrexate (MTX) into four subgroups. The primary efficacy endpoint was extent of improvement in the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) from baseline to 24 weeks assessed as European League Against Rheumatism (EULAR) good response. Secondary endpoints included ADA treatment continuation as represented by Kaplan–Meier survival curves and percentages of patients achieving remission as defined by DAS28-ESR <2.6.

Results Overall, mean DAS28-ESR significantly decreased from 5.6 ± 1.2 at baseline to 4.1 ± 1.7 at week 24 (p < 0.0001), and >30 % of patients achieved EULAR good response. Subgroup analyses indicated that patients in the Bio-naïve and MTX (+) subgroup showed the highest EULAR good response rate of 37.3 % at week 24. The three most commonly reported adverse events (AEs) were skin allergies such as injection-site reactions, infections, and respiratory disorders such as interstitial lung lesions and organizing pneumonia.

Conclusion In conclusion, ADA therapy resulted in significant clinical response in established Japanese patients with RA treated in daily practice. It also demonstrated generally good safety and tolerability. It was suggested that the best use of ADA may be in biologically naïve patients with concomitant administration of MTX.     

Prediction of DAS28-CRP remission in patients with rheumatoid arthritis treated with tacrolimus at 6 months by baseline variables

Abstract

We attempted to determine what baseline variables are responsible for the efficacy of tacrolimus at 6 months in Japanese patients with rheumatoid arthritis (RA). One hundred and six RA patients treated with tacrolimus for 6 months were entered in this study. The outcome was set as the achievement of Disease Activity Score 28 C-reactive protein (DAS28-CRP) remission at 6 months. We examined the association of gender, DAS28-CRP at baseline, concomitant use of methotrexate (MTX), and concomitant use of prednisolone with the achievement of DAS28-CRP remission at 6 months by logistic regression analysis. Twenty-three of 106 patients (21.7%) achieved DAS28-CRP remission at 6 months. There was concomitant use of MTX by 20 patients (18.9%), prednisolone by 93 (87.7%), and prednisolone >5 mg/day by 43 (40.6%) at baseline. Logistic regression analysis showed that male gender (first) and moderate disease activity at baseline (second) are independent predictors toward achieving DAS28-CRP remission at 6 months. Maximum tacrolimus dosage administrated for patients over a 6-month period appeared not to be predictive for the DAS28-CRP remission at 6 months. In conclusion, we revealed for the first time that good outcome in RA patients treated with tacrolimus can be predictive by some baseline variables. That is clinically valuable for daily practice in the choice of disease-modifying antirheumatic drugs (DMARDs), especially tacrolimus.     

Measuring treatment effect on psoriatic arthritis-related domains: insights from the SPIRIT-H2H study at weeks 24 and 52

Introduction

Improvements in both musculoskeletal and non-musculoskeletal manifestations are important treatment goals in psoriatic arthritis (PsA).

Objective

These post hoc analyses determined whether additional benefits related to various PsA domains are observed in patients simultaneously achieving 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100), the primary endpoint of the SPIRIT-H2H study.

Methods

Patients with active PsA and psoriasis in SPIRIT-H2H (N = 566) were categorised into two sets of four response groups irrespective of treatment allocation (approved dosages of ixekizumab or adalimumab): patients who simultaneously achieved ACR50 and PASI100 response, achieved ACR50 response only, achieved PASI100 response only, or did not achieve ACR50 or PASI100 response after 24 and 52 weeks of treatment. Patients achieving simultaneous ACR50 and PASI100 response were compared with the other patient response groups at the corresponding time point for efficacy and health-related quality of life (HRQoL) outcomes.

Results

Patients simultaneously achieving ACR50 and PASI100 responses at week 24 or 52 showed higher rates of ACR70 response, minimal disease activity, Disease Activity in Psoriatic Arthritis ≤ 4, resolution of enthesitis and dactylitis, and HRQoL improvement at weeks 24 and 52, respectively, than the other corresponding response groups at both time points.

Conclusion

High levels of disease control, such as those obtained with simultaneous achievement of ACR50 and PASI100 response, were linked to better outcomes across a wide range of endpoints that are important for patients with PsA. Patients meeting this combined endpoint showed more comprehensive and thus greater control of disease activity.

Trial registration

NCT03151551

Serum Levels of IL-10 and IL-22 Cytokines in Patients with Psoriasis

Background: As a chronic inflammatory condition, psoriasis results from an interaction between genetic and immunologic factors in a predisposing environment. In spite of compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)- 10 and IL-22 have not been sufficiently investigated. Objective: To assess the serum levels of IL-10 and IL-22 in patients with psoriasis compared to healthy controls. Methods: A total of 28 patients with psoriasis were compared with 28 age and sexmatched healthy subjects. Psoriasis Area and Severity Index (PASI) criteria were used to measure the severity of the disease. Serum levels of IL-10 and IL-22 were measured in both groups and compared. Results: The mean serum level of IL-10 was 89.5±18.7 in patients compared to 117.2±23.4 pg/ml in the controls (p=0.36). Also, serum level of IL-22 was 284.1±49.7 in patients versus 425.4±82.8 pg/ml in control group (p=0.17). There was a significant direct correlation between levels of IL-10 and IL-22 in patients group (p=0.0005). The clinical severity of psoriasis was significantly correlated with high levels of IL-22 (p<0.0001).Conclusions: The decreased levels of IL-10 in psoriatic patients and direct correlation between higher levels of IL-22 and disease severity support the clinical implication of both cytokines in psoriasis.     

Involvement of IL-33 in the pathogenesis of rheumatoid arthritis: the effect of etanercept on the serum levels of IL-33

To investigate the role of interleukin (IL)-33 in rheumatoid arthritis (RA) patients, we measured the serum levels of IL-33 in RA patients before and after the administration of etanercept. Twenty-four patients with RA were treated with etanercept. Clinical and laboratory examinations, including serum levels of C-reactive protein (CRP) and hemoglobin (Hb); white blood cell (WBC) and red blood cell (RBC) counts; and the Disease Activity Score of 28 joints including CRP (DAS28-CRP), were performed at the baseline and at 3 and 6 months after the initial treatment with etanercept. The mean serum IL-33 levels had decreased significantly at 3 and 6 months after the initial treatment with etanercept. Serum IL-33 levels showed a significant correlation with the number of tender joints, CRP, DAS28-CRP, and the WBC count, and an inverse correlation with the RBC count and Hb level. These findings indicated that the decrease of serum IL-33 levels was a novel function of etanercept, shown for the first time in this study. Measurement of serum levels of IL-33 may become a useful control marker for RA treatment.