Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study.

BACKGROUND & AIMS: Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). METHODS: This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. RESULTS: In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m2 (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed. CONCLUSIONS: Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

Real-world treatment persistence of four commonly prescribed biologic therapies for moderate to severe psoriasis in Australia.

BACKGROUND/OBJECTIVES: Australian data comparing biologic treatments for moderate to severe chronic plaque psoriasis are lacking. We compared persistence on therapy across four biologic therapies (adalimumab, guselkumab, secukinumab and ustekinumab) used to treat chronic plaque psoriasis. The impact of prior biologic use on persistence was also investigated. METHODS: This retrospective cohort analysis of the Pharmaceutical Benefits Scheme (PBS) 10% sample included data from adult patients prescribed ≥1 biologic of interest by a dermatologist from 1 September 2015 to 31 December 2021. Persistence was defined as continued use until 180 days without a prescription. The index date was the date of the first claim of the biologic. Persistence was evaluated using Kaplan-Meier methods, log-rank tests, adjusted analyses using Cox's regressions, and propensity score matching. RESULTS: In total, 878 patients, with 1131 index prescriptions, were included. Guselkumab median persistence was not reached in the study period (PBS listed from February 2019). In the adjusted analysis, persistence to guselkumab was significantly greater than to adalimumab (n = 105; median 16 months, HR 2.71 (95% CI 1.94-3.8), p < 0.001), ustekinumab (n = 336; median 19 months, HR 2.91 (95% CI 2.22-3.82), p < 0.001) and secukinumab (n = 305; median 30 months, HR 1.8 (95% CI 1.36-2.38), p < 0.001). Bio-naïve patients had longer persistence on treatment than bio-experienced patients. CONCLUSIONS: The nationally representative PBS dataset can provide real-world insights into the persistence on biologic therapies for psoriasis in Australia, where eligibility criteria for reimbursed treatment are stringent. Persistence is an indirect marker of sustained treatment effectiveness and tolerability. Both unadjusted and adjusted analyses found longer persistence for guselkumab compared to adalimumab, secukinumab or ustekinumab.

Effectiveness of biologic therapies in children with palmoplantar plaque psoriasis: An analysis of real-life data from the BiPe cohorts.

BACKGROUND: Palmoplantar plaque psoriasis is a frequent clinical subtype of childhood psoriasis. This study evaluated the effectiveness of biologic therapies in children with palmoplantar plaque psoriasis using data from the two Biological treatments for Pediatric Psoriasis (BiPe) cohorts. METHODS: Data for all 170 patients included in the BiPe cohorts were analyzed. Data on the effectiveness (PGA, PASI between baseline and 3 months of treatment) of biologic therapies were then compared between children with palmoplantar plaque psoriasis (n = 20) and those with generalized plaque psoriasis (n = 136). Clinical and demographic data were also analyzed. RESULTS: Children in the palmoplantar group were more likely to be male (p = .04), with an earlier age of psoriasis onset (p < .001), and more frequent nail involvement (p < .001). After 3 months of biologic treatment, mean PGA scores were higher in the palmoplantar group than in the generalized plaque psoriasis group (p = .004). In the palmoplantar group, continuation rates were higher for adalimumab than for etanercept or ustekinumab (p = .01). Primary inefficacy was a more frequent reason for stopping biologic therapies in the palmoplantar group (p = .01), and disease remission was less frequent (p = .05). Combined systemic and biologic therapies were more frequently used in palmoplantar plaque psoriasis (p < .001). CONCLUSIONS: This study demonstrated the treatment-resistant nature of palmoplantar plaque psoriasis and indicated that adalimumab could be the most effective biologic treatment. Larger studies are needed to allow therapeutic algorithms for palmoplantar plaque psoriasis to be proposed in pediatric psoriasis management guidelines.

Impact of Functional Polymorphisms on Drug Survival of Biological Therapies in Patients with Moderate-to-Severe Psoriasis.

Biological therapies (BTs) indicated for psoriasis are highly effective; however, not all patients obtain good results, and loss of effectiveness is the main reason for switching. Genetic factors may be involved. The objective of this study was to evaluate the influence of single-nucleotide polymorphisms (SNPs) on the drug survival of tumor necrosis factor inhibitors (anti-TNF) medications and ustekinumab (UTK) in patients diagnosed with moderate-to-severe psoriasis. We conducted an ambispective observational cohort study that included 379 lines of treatment with anti-TNF (n = 247) and UTK (132) in 206 white patients from southern Spain and Italy. The genotyping of the 29 functional SNPs was carried out using real-time polymerase chain reaction (PCR) with TaqMan probes. Drug survival was evaluated with Cox regression and Kaplan-Meier curves. The multivariate analysis showed that the HLA-C rs12191877-T (hazard ratio [HR] = 0.560; 95% CI = 0.40-0.78; p = 0.0006) and TNF-1031 (rs1799964-C) (HR = 0.707; 95% CI = 0.50-0.99; p = 0.048) polymorphisms are associated with anti-TNF drug survival, while TLR5 rs5744174-G (HR = 0.589; 95% CI = 0.37-0.92; p = 0.02), CD84 rs6427528-GG (HR = 0.557; 95% CI = 0.35-0.88; p = 0.013) and PDE3A rs11045392-T together with SLCO1C1 rs3794271-T (HR = 0.508; 95% CI = 0.32-0.79; p = 0.002) are related to UTK survival. The limitations are the sample size and the clustering of anti-TNF drugs; we used a homogeneous cohort of patients from 2 hospitals only. In conclusion, SNPs in the HLA-C, TNF, TLR5, CD84, PDE3A, and SLCO1C1 genes may be useful as biomarkers of drug survival of BTs indicated for psoriasis, making it possible to implement personalized medicine that will reduce financial healthcare costs, facilitate medical decision-making and improve patient quality of life. However, further pharmacogenetic studies need to be conducted to confirm these associations.

Drug utilization of biologic therapy in Crohn's disease and ulcerative colitis: a population-based Danish cohort study 2015-2020.

OBJECTIVE: The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015-2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression. RESULTS: Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD.When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29-0.89]), and for CD patients, although not significantly (0.58 [0.32-1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics. CONCLUSION: More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.Key summarySeveral biologic therapies are available in the treatment of ulcerative colitis and Crohn's disease.Clinical guidelines stipulate that infliximab should be the first-line biologic therapy.Drug utilization studies comparing biologic therapies head-to-head are sparse.In Denmark, during 2015-2020 infliximab remained the most widely used biologic treatment, with adalimumab being second.One in four patients experienced more than one biologic during the study period.The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab.Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.

Prompt and Sustained Suppression of Intraocular Inflammation with Adalimumab in Pediatric Patients with Non-Infectious Uveitis Resistant to Traditional Managements: A 6-Month Follow-Up Research.

PURPOSE: To assess the efficacy of adalimumab (ADA) on visual acuity (VA), ocular inflammation, vitreous haze and central macular thickness (CMT) in pediatric refractory non-infectious uveitis. METHODS: Thirty-one eyes of 16 pediatric patients with uveitis of various etiologies were treated with ADA. VA, intraocular active inflammatory cells, vitreous haze, and CMT were evaluated at the baseline and 2nd, 4th, 12th, and 24th weeks following ADA treatment. RESULTS: Twenty-three of 31 eyes had active and the remaining 8 eyes had inactive uveitis (with frequent relapse) before ADA therapy. VA (LogMAR) increased at 12th week following ADA treatment (p< .001). Intraocular inflammation degrees significantly improved within 4 weeks (p< .001). Vitreous haze decreased at fourth week and stabilized at 12th week (p= .038). CMT started to decrease within weeks and stabilized at 12th week (p= .006). CONCLUSIONS: ADA was found to be safe and effective to suppress intraocular inflammation in pediatric non-infectious uveitis, which prevented sight-threatening complications.

Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn's disease: systematic review and network meta-analysis.

OBJECTIVE: There are numerous biological therapies and small molecules licensed for luminal Crohn's disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis. DESIGN: We searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score. RESULTS: We identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82). CONCLUSION: In a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission.

Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn's Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD. METHODS: We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55). CONCLUSIONS: Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.

Despite the era of biologic therapies, the management of fistulizing Crohn's disease remains challenging. This is the first systematic review and network meta-analysis to compare the efficacy of biologic therapies in inducing response and remission in patients with fistulizing Crohn's disease. We found that anti-tumor necrosis factor agents are effective in inducing response and remission. Infliximab was superior to adalimumab for inducing response but not for inducing remission.

IgA Vasculitis in the Setting of Biologic Therapy for Psoriasis and Recurrent Cutaneous Methicillin-Resistant Staphylococcus aureus Colonization.

IgA vasculitis is a form of cutaneous small-vessel leukocytoclastic vasculitis (LCV) that has various triggers, including anti-tumor necrosis factor (TNF) α therapy. As the use of more targeted biologic therapies such as the IL-17 inhibitor secukinumab increases, so do reports of associated adverse events. Herein, we describe an uncommon case of IgA vasculitis in a man undergoing biologic therapy with adalimumab and secukinumab for psoriasis with recurrent cutaneous methicillin-resistant Staphylococcus aureus (MRSA) colonization. A review of the current literature also is provided.

Tapering biologics in axial spondyloarthritis: A systematic literature review.

INTRODUCTION: The emergence of biologics has improved the management of patients with rheumatic disease, mainly with spondyloarthritis (SpA). Sustained remission has become a reachable goal thanks to the treat to target strategy. Contrary to rheumatoid arthritis, data on biologic optimization among SpA patients in remission is scarce and still a subject of debate. The main objective of this systematic review was to provide the most up-to-date published literature regarding biologic tapering in axial spondyloarthritis. METHODS: This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until December 20th 2021, and tackling tapering strategies of the biologics in patients with axial SpA were included RESULTS: Fourteen studies met the inclusion criteria. They were published between 2008 and 2020. The most studied molecules were Etanercept (ETN) (n = 13), Infliximab (IFX) (n = 6), Adalimumab (ADA) (n = 5), certolizumab pegol (CZP) (n = 2), Golimumab (n = 1) and ETN biosimilar. There are no studies published regarding anti-IL 17 tapering strategy. Patient-tailored dose reduction of anti TNF-α agents was successful in preserving stable low disease activity in most of the studies with remission rates ranging between 20.2 % and 93.7 %. Complete treatment discontinuation is associated with a high risk of flares. CONCLUSION: To conclude, published data indicate that a progressive tapering strategy for anti TNF-α therapy is successful among axial SpA in sustained remission. However, further studies with more homogenized tapering strategies are needed in order to ascertain the specific implication of each subset for a better holistic approach.

Adalimumab therapy is associated with increased faecal short chain fatty acids in hidradenitis suppurativa.

Altered gut microbiota composition has been observed in individuals with hidradenitis suppurutiva (HS) and many other inflammatory diseases, including obesity, type 1 and type 2 diabetes. Here, we addressed whether adalimumab, a systemic anti-inflammatory therapy, may impact the microbiota biochemical profile, particularly on beneficial metabolites such as short-chain fatty acids (SCFAs). We conducted an observational single-arm pilot trial to assess gut microbiota composition by 16S rRNA gene sequence analysis and to detect metabolite signatures by gas chromatography in stool samples from participants with HS prior to and 12 weeks after commencing adalimumab therapy. HS individuals that better responded to adalimumab treatment showed a shift in the composition and function of the gut microbiota with significantly increased SCFA acetate and propionate compared to age, gender and BMI-matched healthy controls. A positive correlation was observed between propionate with Prevotella sp and Faecalibacterium prausnitsii. Increased SCFAs, changes in gut microbiota composition, function and metabolic profile following 12 weeks of adalimumab suggest that targeting SCFAs may be considered a potential biomarker to be evaluated as a complementary protective factor or as a diagnostically relevant signal in HS.

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Adalimumab Mitigates Lumbar Radiculopathy in a Case of Ankylosing Spondylitis.

BACKGROUND Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory condition grouped under spondyloarthritis (SpA), which is an umbrella term for a group of interrelated inflammatory rheumatic conditions with characteristic radiographic findings such as erosions and ankylosis of the sacroiliac joint. Unfortunately, there is an average delay of 8-9 years between the onset of the symptoms and diagnosis due to infrequent consideration of this disease in the differential diagnosis of patients with low back pain and unusual or incomplete presenting clinical symptoms. CASE REPORT We describe the case of a 37-year-old male patient with no significant past medical history and surgical history of bilateral hip arthroplasty secondary to idiopathic aseptic necrosis of the bilateral femoral head and bilateral rotator cuff repaired surgery due to multiple motor vehicle accidents (MVA) with a chief concern of chronic low back pain. In this case of ankylosing spondylitis presenting with low back pain and radicular symptoms, his symptoms were resistant to multiple opioid medications, trigger point injections, and epidural steroid injections. Initiation of adalimumab subsequently relieved the patient's symptoms and restored his ability to perform daily activities. CONCLUSIONS This is an unusual presentation of AS with radiographic evidence of bilateral sacroiliitis. The neurological manifestations in AS are not uncommon, and they can occur during the quiescent stage of the disease. It should be emphasized that early diagnosis is essential to prevent progression of the disease and avoid unnecessary treatment for the patient.

Adalimumab or etanercept as first line biologic therapy in enthesitis related arthritis (ERA) - a drug-survival single centre study spanning 10 years.

OBJECTIVES: To analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis). METHODS: In this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009-2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions. RESULTS: During the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9-5.7) for adalimumab, compared to 2years (95%CI 1.4-4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32--0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20-0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15-0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21-0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29-0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08-2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22-3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13--3.64). CONCLUSION: Following an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings.

Differential Impact of Biologic Therapy on Heart Function Biomarkers in Rheumatoid Arthritis Patients: Observational Study on Etanercept, Adalimumab, and Tocilizumab.

BACKGROUND: Rheumatoid arthritis (RA) represents the most frequent form of inflammatory arthritis, affecting approximately 1% of the population worldwide. The introduction of novel therapeutic strategies targeting proinflammatory cytokines (TNF-α and interleukin-6) revolutionized the treatment of RA. This kind of treatment, although effective in a substantial portion of patients, may potentially cause many side effects. Among them, cardiovascular safety is one of the main concerns. OBJECTIVES: In the present study, we investigated the impact of treatment with anti-TNF-α and anti-IL-6 agents on heart function and levels of heart function biomarkers. METHODS: To measure this, we used cardiac function biomarkers, such as NT-pro Brain Natriuretic Peptide, mid regional pro-Atrial Natriuretic Peptide, Galectin-3, and Heart-Type Fatty Acid-Binding Protein and compared them to patients treated with methotrexate as well as healthy controls. RESULTS: Patients treated with biologics were characterized by low disease activity or were in remission. The disease activity in these groups was significantly lower than in the methotrexate group. All patients recruited for the study were characterized by normal heart function measured using echocardiography (EF>50%). With the exception of MR-proANP between tocilizumab and adalimumab (median: 1.01 vs. 0.49 nmol/L, p<0.05), we failed to observe any significant differences in biomarkers levels between groups treated with biologics. Contrary to this, patients on MTX showed higher NT-proBNP levels compared to adalimumab and healthy controls (p<0.05 for both). Striking differences have been shown in regard to H-FABP. The levels of these biomarkers were elevated in all biologics and the methotrexate group compared to healthy controls. CONCLUSION: As this biomarker reflects potential heart injury, we suggest that heart damage proceeds in a continuous manner in RA patients despite effective treatment and attainment of remission/low disease activity. This finding, however, should be verified in a larger cohort of RA patients to ascertain if the routine assessment of H-FABP may be useful for the detection of patients with RA who are at risk of development of heart damage.

Combining biological therapies in patients with inflammatory bowel disease: a Finnish multi-centre study.

BACKGROUND AND AIMS: Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. MATERIALS AND METHODS: Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. RESULTS: A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). CONCLUSION: DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.

Biologic therapy in refractory neurobehçet's disease: a multicentre study of 41 patients and literature review.

OBJECTIVES: To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug. METHODS: Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters. RESULTS: We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment. CONCLUSIONS: BT appears to be effective and relatively safe in refractory NBD.

Deferred time of delivery of biologic therapies in patients with stabilized psoriasis leads to a 'perceived satisfaction': a multicentric study.

OBJECTIVE: Thanks to their specificity of action, biologic drugs often lead to complete clearance of psoriatic lesions. In order to maintain its effectiveness, biological therapies cannot be discontinued. The aim of the study was to investigate the effect of widening the administration window of four biologic drugs, thus improving the quality of life of psoriatic patients and satisfying their desire to feel free from the disease, without loss of effectiveness. METHODS: We performed a multicentric cohort study considering patients with moderate-severe plaque psoriasis and/or arthropathic psoriasis treated with infliximab, adalimumab, etanercept or ustekinumab. The study group included patients with stabilized psoriasis in which the administration regimen of the biologic drug was deferred. The control group included psoriatic patients treated according the product monograph. RESULTS: The percentage of relapses in case of deferred administration intervals was comparable to that of standard administration intervals. The delayed administration modality got a good psychological consensus from the patients themselves, that reported a greater 'perceived satisfaction'. A consistent economic advantage was reported in case of prolonged administration intervals. CONCLUSIONS: The administration of biologic drugs with prolonged intervals maintains the same effectiveness as standard administration and produces a 'perceived satisfaction' in psoriatic patients.

Predictors of drug survival of biologic therapies in psoriasis patients.

INTRODUCTION: We aimed to investigate the clinical, immunological, and genetic factors affecting the response to anti-TNFα (tumor necrosis factor-α) and interleukin-12/23 therapies and drug survivals. METHODS: A total of 180 patients were divided into two groups: 89 patients who used at least two biologic agents, with the initial biologic agent used less than 12 months (group A), and 91 biologic-naive patients who have been receiving a single biologic agent for more than 12 months (group B). ELISA (enzyme-linked immunosorbent assay) was used to analyze anti-drug antibodies (ADAs) in blood samples. Clinical data of the patients were retrospectively analyzed. HLA-SSO (sequence-specific oligonucleotide) Typing Kits were used for HLA-C typing. IBM SPSS v.21 was used for statistical analysis.Results: Infliximab had the longest drug survival as the first biologic agent in group A (p = .015). Etanercept had the lowest ADA count compared to the other anti-TNF agents (p = .001). HLA-Cw6 negativity, late-onset psoriasis, smoking and alcohol use were determined to be risk factors for treatment failure in group A. HLA-Cw6 was found to be associated with type I psoriasis (p = .000). CONCLUSIONS: Although our study is retrospective of a relatively low number of patients, this is a preliminary study focusing on two different patient populations based on therapy response.