Increased circulating anti‐α6‐integrin autoantibodies in psoriasis and psoriatic arthritis but not in rheumatoid arthritis

In psoriatic skin, laminin integrity is altered, which could lead to insufficient laminin integrin interactions, leaving the α6‐integrin exposed and possibly accessible for autoantibody production. Therefore we investigated the presence of anti‐α6‐integrin autoantibodies in the serum of patients with psoriasis vulgaris (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in comparison with healthy donors. The level of circulating anti‐α6‐integrin antibodies was determined by enzyme‐linked immunoassay using α6‐integrin fragments. Antibodies against at least one recombinant fragment were found in approximately 30% of Ps and PsA patients. In contrast, in RA patients, the frequency of antibodies was similar to healthy controls. Our study shows the presence of anti‐α6‐integrin antibodies in Ps and PsA but not in RA, which could indicate ongoing abnormal processes in the skin. Anti‐α6‐integrin autoantibodies may contribute to the formation of micro‐wounds in the skin and to the characteristic wound‐healing phenotype in psoriasis.     

Effects of anti‐TNF‐α agents on circulating endothelial‐derived and platelet‐derived microparticles in psoriasis

Psoriasis involves TNF‐α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti‐TNF‐α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti‐TNF‐α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti‐TNF‐α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/μl vs 1849/μl, P = 0.02) and of endothelial microparticles (64/μl vs 22/μl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti‐TNF‐α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles.     

New onset or transition of disease state of psoriatic arthritis during treatment with ustekinumab: A single‐center retrospective study

Ustekinumab (UST) is a treatment option for psoriatic arthritis (PsA), but recent observations indicate that some psoriatic patients may experience new onset of PsA or worsening of pre‐existent PsA. We retrospectively analyzed all cases of psoriasis vulgaris (PsV) and PsA treated with UST in our facility between 2011 and 2015. PsA developed in eight out of 179 PsV patients, mostly later than 8 months after initiation of UST. It was generally not severe, and none had received tumor necrosis factor (TNF)‐α inhibitors previously, indicating that the possibility of unmasking pre‐existing subclinical arthritis is minimal. The eruptions were well controlled at the time of the onset of arthritis in most cases. Interestingly, those who developed arthritis showed a significantly lower body mass index. Regarding pre‐existing PsA, nine PsA patients received UST, and at least partial improvement of PsA could be achieved in two out of three bio‐naive and three out of six bio‐switched patients from TNF‐α inhibitors. PsA was largely more refractory to UST than the eruptions. Altogether, our present study is in agreement with the notion that UST may be less efficient than TNF‐α inhibitors for PsA. While UST cannot fully prevent new development of PsA, it is unlikely that UST increases the risk of new onset of PsA as a paradoxical adverse reaction.     

Anti‐tumor necrosis factor‐alpha therapy improves endothelial function and arterial stiffness in patients with moderate to severe psoriasis: A 6‐month prospective study

The aim of the present study was to determine if the use of the anti‐tumor necrosis factor (TNF)‐α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m² or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow‐mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty‐nine patients were studied. Anti‐TNF‐α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti‐TNF‐α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis.     

TNF‐alpha‐Antagonisten in der Therapie der Psoriasis – Nutzen und Risiken

Summary: Anti‐TNF‐α agents including etanercept, a fusion protein of the p75 TNF receptor and IgG1 and infliximab, a chimeric human‐mowie monoclonal antibody. They have been approved for the treatment of rheumatoid arthritis and/or Crohn's disease. New understanding of the importance of the inlammatory cytokine TNF‐α in the pathophysiology of psoriasis led to the use in open‐label and randomized studies in patients with psoriasis and psoriatic arthritis. Although larger randomized trials are needed to confirm early results, both anti‐TNF‐α agents, have demonstrated activity in improving the signs and symptoms of psoriatic arthritis and psoriasis. Further investigations will fully elucidate the role of infliximab in these and other dermatological diseases.     

Cutaneous events during treatment of chronic inflammatory joint disorders with anti‐tumour necrosis factor alpha: a cross‐sectional study

Background Anti‐tumour necrosis factors (anti‐TNF) are more and more used, but the rate of skin adverse events is not known. Objective The aim was to assess the number of skin infections and other dermatoses in patients treated with anti‐TNFα. Patients and methods One hundred eighty‐seven patients suffering from rheumatoid arthritis or ankylosing spondylitis underwent a dermatological exam. Patients with anti‐TNF were compared with those without this treatment in a prospective transversal study. Results Among them, 59 patients were treated with anti‐TNFα and steroids were prescribed in 100 cases. There was no difference in the prevalence of skin infections or eczema or tumours. Skin drug reactions were observed in six patients. Infections by dermatophytes appear very frequent, approaching 70% in both groups. Conclusions This study shows that skin infections (or other skin diseases) are not more frequent in these patients. No differences were observed in infections (bacterial fungal, parasital or viral), tumours, psoriasis or the manifestations of atopic dermatitis. Nonetheless, a long‐term survey might be interesting, especially about skin tumours.     

Psoriasis and bone mineral density: Implications for long‐term patients

Psoriasis is a chronic inflammatory disease associated with several comorbidities. Osteoporosis is defined as a reduction in bone mineral density with impaired bone microarchitecture. Several mechanisms may be implicated as a possible cause for the association between psoriasis and osteoporosis, such as systemic inflammation, anti‐psoriatic drug intake and joint dysfunction for psoriatic arthritis (PsA). The aim of the present study was to assess bone mineral density (BMD) in patients with psoriasis, correlating the prevalence of osteopenia/osteoporosis with Psoriasis Area and Severity Index (PASI) score, mean duration of psoriatic disease, PsA and previous treatments for psoriasis. Forty‐three consecutive patients with psoriasis, 19 of whom were affected by the arthropathic form, were enrolled. We evaluated the severity of psoriasis as measured by PASI score, the CASPAR criteria and ultrasounds of the joints to verify the diagnosis of PsA and the age of psoriasis onset to estimate mean disease duration. Patients underwent a bone density scan of the lumbar spine and femoral neck by dual‐energy X‐ray absorptiometry to measure BMD. Patients with osteopenia/osteoporosis showed a statistically significant longer average duration of psoriatic disease (17 years), compared to patients affected by psoriasis with normal T‐score (8.8 years) (P = 0.04). The linear logistic regression confirms a significant relation between mean psoriatic disease duration and BMD alterations (P = 0.04). Our results suggest the necessity of an early diagnostic evaluation of bone metabolism in patients with psoriasis, especially if characterized by longer disease duration.     

IL‐33 is secreted by psoriatic keratinocytes and induces pro‐inflammatory cytokines via keratinocyte and mast cell activation

IL‐33 is a novel pro‐inflammatory cytokine and ligand for the orphan receptor ST2. Although originally defined as an inducer of Th2‐mediated responses, IL‐33 was recently found to be involved in arthritis, a Th1/Th17‐mediated disease. Here, we assessed the ability of IL‐33 to promote inflammation via mast cells (MCs) and keratinocytes (KCs) activation in psoriasis. IL‐33 resulted elevated in the skin but not in the serum of psoriasis patients. IL‐33 was secreted by psoriasis KCs and HaCaT cells after TNF‐α stimulation. In HMC‐1, TNF‐α, but not IL‐17, could induce a robust increase in IL‐33 expression. In HaCaT cells, TNF‐α was able to induce IL‐6, MCP‐1 and VEGF, and the addition of IL‐33 reinforced these increases. TNF‐α + IL‐33 combination showed similar results in primary KCs and ex vivo skin organ culture. In conclusion, our study suggests that IL‐33 may be involved in psoriasis biology via MCs and KCs.     

Adalimumab‐Induced Cutaneous Lupus Erythematosus in a 16‐Year‐Old Girl with Juvenile Idiopathic Arthritis

Tumor necrosis factor α (TNF‐α) antagonists are used in the treatment of numerous autoimmune conditions. Adalimumab is the first monoclonal antibody to TNF‐α and is used to treat juvenile idiopathic arthritis. A growing body of literature associates anti‐TNF‐α therapies with several adverse dermatologic manifestations, including drug‐induced lupus erythematosus (LE). We describe a case of cutaneous LE in a 16‐year‐old girl treated with adalimumab for juvenile idiopathic arthritis. The temporal association between her presenting symptoms and adalimumab initiation and gradual improvement after stopping biologic therapy suggest adalimumab‐induced cutaneous LE. With increasing use of anti‐TNF therapies in children, the potential for drug‐induced LE should not be overlooked.     

Anti–tumour necrosis factor-α therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study

Background Chronic plaque psoriasis is associated with overweight or obesity. Anti–tumour necrosis factor‐α (anti‐TNF‐α) treatments are now frequently used in psoriasis management. TNF‐α is deeply involved in body weight homeostasis, which may be affected by TNF‐α–targeted therapy. Objective To investigate whether anti‐TNF‐α treatments is associated with changes in body weight in patients with chronic plaque psoriasis. Methods We performed a retrospective controlled analysis comparing the variations in body weight and body mass index (BMI) in three closed cohorts of psoriatic patients during a 6‐month treatment with etanercept (N = 58), infliximab (N = 40) or methotrexate (N = 43). Results We observed a body weight increment of 1.5 ± 2.7 kg (mean ± SD; P = 0.0002) and 2.5 ± 3.3 kg (P = 0.004) in patients treated with etanercept and infliximab, respectively. In contrast, a non‐significant change (0.6 ± 1.4 kg; P = 0.4) was measured in patients treated with methotrexate. The BMI increased with 0.5 ± 0.5 (P = 0.01) and 0.8 ± 1 (P = 0.003) points in patients treated with etanercept and infliximab, respectively, whereas it did not change (< 0.2 ± 0.5; P = 0.06) in patients treated with methotrexate. About one fourth of patients experienced a 4‐ to 10‐kg weight gain. Differences in body weight variations among patients treated with anti‐TNF‐α therapies and methotrexate were statistically significant (P = 0.0005). We could not identify clinical parameters predicting this phenomenon. Conclusions Patients with psoriasis treated with long‐term anti‐TNF‐α therapies may manifest a body weight gain. This effect should be taken into account in the global approach to patients with psoriasis.     

Drug‐induced lupus erythematosus with emphasis on skin manifestations and the role of anti‐TNFα agents

Drug‐induced lupus erythematosus (DILE) is a lupus‐like syndrome temporally related to continuous drug exposure which resolves upon drug discontinuation. There are currently no standard diagnostic criteria for DILE. Findings include skin manifestations, arthritis, serositis, anti‐nuclear and anti‐histone antibodies positivity. Similarly to idiopathic lupus erythematosus, DILE can be divided into systemic (SLE), subacute cutaneous (SCLE) and chronic cutaneous lupus (CCLE). Systemic DILE presents as a milder version of idiopathic SLE, and the drugs most frequently implicated are hydralazine, procainamide and quinidine. Anti‐TNFα therapies are the latest class of medications found to be associated, although rarely, with a “lupus‐like” syndrome, which is however clinically distinct from classical DILE. Drug‐induced SCLE is the most common form of DILE. It is very similar to idiopathic SCLE in terms of clinical and serologic characteristics. The most commonly implicated drugs are antihypertensive drugs and terbinafine, but in recent years also proton pump inhibitors and chemotherapeutic agents have been associated. Drug‐induced CCLE is very rare and usually caused by fluorouracil agents and NSAIDS, but some cases have induced by pantoprazole and anti‐TNFα agents.     

Antinuclear antibodies associate with loss of response to antitumour necrosis factor‐α therapy in psoriasis: a retrospective,observational study

Background An increasing number of patients with severe psoriasis are failing to respond to antitumour necrosis factor (TNF)‐α therapy (etanercept, infliximab and adalimumab). Objectives We observed that many of these patients developed antinuclear antibodies (ANA) and antidouble‐stranded DNA (anti‐dsDNA) antibodies while on treatment prompting us to investigate whether their development is associated with anti‐TNF treatment failure. Methods All patients with psoriasis who had received anti‐TNF therapies were identified and their blood results and treatment histories were obtained from electronic patient records and case notes. Results A total of 97 patients had been treated with anti‐TNF agents (60 were on their first agent, 22 had been on and stopped one agent, nine had been on and stopped two agents and six had been on and stopped all three agents). ANA developed in 17% of patients on their first treatment, 54% of patients who had failed one treatment, 78% of patients who had failed two treatments and 83% of patients who had failed all three treatments. Anti‐dsDNA antibodies developed in 2%, 27%, 33% and 83% of patients from the same respective groups. Significantly, the antibodies developed before treatment had failed with all three agents and their development was not related to the total time that patients had been on anti‐TNF therapy. Conclusions This study suggests that the development of ANA and anti‐dsDNA antibodies on anti‐TNF treatment may act as a marker of forthcoming treatment failure. Large‐scale prospective studies are required to assess the importance of this observation.     

Efficacy comparison of ustekinumab between anti‐tumor necrosis factor‐α drug‐naïve and anti‐tumor necrosis factor‐α drug‐resistant Japanese psoriasis cases

Ustekinumab is highly efficacious for psoriasis; however, it has not been fully clarified whether previous failure in anti‐tumor necrosis factor‐α (TNF‐α) therapy affects the treatment response with ustekinumab. Therefore, we evaluated the efficacy of ustekinumab in anti‐TNF‐α‐naïve and anti‐TNF‐α‐resistant cases and compared the clinical efficacies of adalimumab and ustekinumab in biologic naïve cases. Thirty‐five patients with plaque psoriasis who showed resistance to conventional therapies were enrolled; 26 patients, who had never been treated with biologics, were allocated to ustekinumab or adalimumab; nine patients who failed to achieve psoriasis area and severity index (PASI) 50 at week 16 with one or two TNF‐α antagonists were switched to ustekinumab. The end of the study was defined as 52 weeks after starting the first biologic for anti‐TNF‐α‐naïve patients and after switching to ustekinumab for anti‐TNF‐α‐resistant patients. The primary outcome measurement was the percentage of patients achieving PASI75 at week 16. In patients treated with ustekinumab, 87.5% of anti‐TNF‐α‐naïve and 77.8% of anti‐TNF‐α‐resistant cases achieved a PASI75 response at week 16, and no statistically significant difference was found between the treatment response rates (P = 0.60). When comparing the treatment efficacy of ustekinumab and adalimumab among anti‐TNF‐α‐naïve patients, there was also no statistically significant difference in PASI75 achievement rates (87.5 vs. 83.3%, P = 0.79). Our study suggests that ustekinumab can be considered as a first‐line biologic for psoriasis and a rescue therapy for anti‐TNF‐α‐resistant cases.     

TNF‐α and IL‐10 gene polymorphisms show a weak association with pemphigus vulgaris in the Slovak population

Backround Pemphigus vulgaris is a rare chronic autoimmune disease of skin and mucous membranes, with several cytokines participating in its development. The role of their gene polymorphisms in susceptibility to the disease is, however, not fully understood. Objective The aim of our case‐control study was to investigate whether some of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes (IL‐1α, IL‐1β, IL‐1RI, IL‐1Ra, IL‐4Rα, IL‐12, IFN‐γ, TGF‐β1, TNF‐α, IL‐2, IL‐4, IL‐6 and IL‐10) are associated with pemphigus vulgaris in the Slovak population. Methods DNA samples were obtained from 34 pemphigus vulgaris patients and 140 healthy controls of Slovak origin. Cytokine gene SNPs were determined using the polymerase chain reaction with sequence‐specific primers (PCR‐SSP) method. Results We found a weak association between pemphigus vulgaris and polymorphic variants in TNF‐α and IL‐10 genes only, with haplotypes TNF‐α–308G/–238G and IL‐10 –1082A/–819C/–592C being significantly overrepresented in pemphigus vulgaris patients (TNF‐α GG: 94.12% vs. 82.86%, P = 0.0216; IL‐10 ACC: 44.12% vs. 30.00%, P = 0.0309). Conclusions Our preliminary results suggest that certain TNF‐α and IL‐10 gene polymorphisms might contribute to genetic susceptibility to pemphigus vulgaris; however, their overall impact on disease development will be rather limited.     

Genetic prediction of the effectiveness of biologics for psoriasis treatment

Anti‐tumor necrosis factor (TNF)‐α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome‐wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti‐TNF‐α therapy using Human Omni Express‐8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti‐TNF‐α agents (strongest effect, P < 7.11E‐06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti‐TNF‐α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF‐α production, was previously reported to be associated with treatment responses to TNF‐α inhibitors.     

Development of MGUS in psoriatic patients: a possible undiagnosed event during anti‐TNF‐α‐treatment

Background Monoclonal gammopathies are haematological conditions characterized by the clonal proliferation of plasma cells which produce a monoclonal immunoglobulin that accumulates in the blood. They have already been reported during treatment with a range of drugs but never before during treatment with the anti‐TNF‐α treatments: adalimumab, etanercept and infliximab currently used in the therapy of moderate‐severe psoriasis and psoriatic arthritis. Objective This is a case series describing the development of MGUS in psoriatic patients treated with anti‐TNF‐α. Methods Three hundred patients receiving an anti‐TNF‐α treatment for chronic plaque psoriasis or psoriatic arthritis in a clinical setting in Italy, These patients were screened through serum protein electrophoresis to investigate the possible development of MGUS. Results Eight patients were found to have developed monoclonal gammopathy of undetermined significance. The median treatment duration for the eight patients was 1 year with excessive IgG present in five patients, IgM accumulation in one patient and a double monoclonal component in two patients. Conclusion Our data suggest that there may be an association between anti‐TNF‐α therapy and development of MGUS.     

Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate‐to‐severe psoriasis undergoing anti‐tumor necrosis factor‐α therapy

Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate‐to‐severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti‐tumor necrosis factor (TNF)‐α therapy in these patients. This was a prospective study on a series of consecutive non‐diabetic patients with moderate‐to‐severe psoriasis who completed 6 months of therapy with anti‐TNF‐α‐adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m² or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty‐nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6‐month BSA change compared with baseline results. In patients with moderate‐to‐severe psoriasis, ADMA levels correlate with clinical markers of disease severity.     

Body weight increment in patients treated with infliximab for plaque psoriasis

Background Psoriasis is frequently associated with overweight and obesity. Anti‐TNF‐α therapies are effective in the treatment of psoriasis. TNF‐α is highly involved in body weight regulation. Objective Our objective was to evaluate the increase in weight throughout the treatment with infliximab and the association of weight gain with the body mass index (BMI). Methods Thirty‐five patients affected with severe plaque psoriasis receiving infliximab were included. A control group consisted of 16 patients affected with severe plaque psoriasis and treated with cyclosporine, methotrexate, or acitretin. Assessment of PASI score, body weight and BMI were performed at a 1 and 3‐year follow‐up. Results We observed a body weight increment of 2.5 ± 4.4 kg (mean ± SD) (i.e. + 3.6% of baseline) and 0.1 ± 5 kg (i.e. + 1.2%) in patients treated with infliximab and the control group, respectively (P = 0.046), after 1 year of treatment. After 3 years of infliximab administration, weight gain was 4.8 ± 5 kg (n = 16) (i.e. + 6%) (P = 0.005). Moreover, as classified by BMI, normal weight patients experienced a 4 ± 3.7 kg weight gain (i.e. + 6%) whereas overweight and obese patients had gained 1.3 ± 4.8 kg (i.e. + 1.2%) (P = 0.039) after 1 year of anti‐TNF‐α therapy. Percentual changes in body weight were larger in normal weight patients at baseline than in overweight/obese counterparts (P = 0.0149). Conclusion All patients, including normal weight patients, should receive a dietary intervention.     

Associations between anti‐melanoma differentiation‐associated gene 5 antibody and demographics,clinical characteristics and laboratory results of patients with dermatomyositis: A systematic meta‐analysis

Anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody is a specific biomarker in patients with dermatomyositis (DM). Results from several studies that examined the relationship between anti‐MDA5 antibody and the demographics, clinical characteristics and laboratory results of DM patients have been conflicting. The purpose of this study was to identify the relationship, if any, of anti‐MDA5 antibody with demographics, clinical characteristics and laboratory results of DM patients. PubMed, Web of Science, Embase and the Cochrane Library databases were searched for studies without language restrictions conducted before 16 March 2017. Stata version 12.0 software was used to calculate pooled odds ratios or weighted mean differences and corresponding 95% confidence intervals to determine the relationship between anti‐MDA5 antibody and patient characteristics. Twenty studies comprising 1500 cases were included in this meta‐analysis. Anti‐MDA5 antibody was strongly associated with clinically amyopathic DM (CADM) and rapidly progressive interstitial lung disease (RPILD). Anti‐MDA5 antibody also increased the risk of developing eight characteristics comprising Gottron's sign or papules, mechanic's hand, V rash, skin ulcers, panniculitis, alopecia, arthritis/arthralgia and pneumomediastinum, but reduced the risk of muscle weakness, classic DM (CDM) and elevated creatine kinase (CK). Our meta‐analysis indicated that anti‐MDA5 antibody is related to muscle weakness, Gottron's sign or papules, mechanic's hand, V rash, skin ulcers, panniculitis, alopecia, arthritis/arthralgia, pneumomediastinum, RPILD, CDM, CADM and elevated CK in patients with DM.     

Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris

Background Adherence to treatment is an indicator of treatment success. Long‐term data on adherence to biologic treatment in psoriasis are lacking. Objectives To compare the tumour necrosis factor (TNF)‐α inhibitors regarding drug survival rate and safety in patients with psoriasis. Methods This study is based on data from the Danish nationwide database DERMBIO covering patients with psoriasis treated with a biologic agent. All patients who received anti‐TNF‐α treatment in academic referral centres were included. Baseline data, adverse events, time on treatment and reason for stopping treatment were recorded. Hazard ratios (HRs) for factors determining drug survival were calculated by logistic regression. Results In total, 882 treatment series with etanercept (n = 311), adalimumab (n = 427) or infliximab (n = 144) were administered to 747 patients. Significant predictors of drug survival were: sex, the anti‐TNF‐α agent and the previous response to an anti‐TNF‐α agent. In the group of anti‐TNF‐α‐naïve patients the longest drug survival was observed for infliximab, followed by adalimumab [HR vs. infliximab 3·70, 95% confidence interval (CI) 1·99–6·89] and etanercept (HR vs. infliximab 3·18, 95% CI 1·72–5·86). The 4‐year drug survival is in the range of 40% for etanercept or adalimumab vs. 70% for infliximab. There was no difference in number of adverse events. Conclusions The overall efficacy of anti‐TNF‐α drugs diminishes with time, as envisaged by the progressive loss of patient adherence to treatment. The major reasons for stopping treatment were loss of efficacy, followed by adverse events. Infliximab had the best patient retention ability, with 70% of patients still being on the drug after 4 years of treatment.