Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis.

BACKGROUND: Psoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA. METHODS: We searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence. RESULTS: We included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety. CONCLUSIONS: In conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available. PROTOCOL REGISTRATION: PROSPERO: CRD42022315577.

A case of certolizumab-induced purpura annularis telangiectodes of Majocchi and literature review.

Tumor necrosis factor alpha (TNFα) inhibitors are now widely used to treat immune-mediated inflammatory diseases. Although they have a good safety profile, they are also associated with adverse cutaneous events. Pigmented purpuric dermatoses (PPD) include a variety of skin diseases characterized by multiple petechial hemorrhages due to capillaritis. Five major clinical types of PPD have been described and purpura annularis telangiectodes of Majocchi (PATM) is a rare subtype of PPD. The cause of PPD is unknown, but drugs are implicated in a minority of cases. There are very few cases in the literature triggered by TNFα inhibitors. We present a case of PATM induced by certolizumab pegol and perform a review including 4 articles in the literature reporting 5 PPD cases induced by TNFα inhibitors. When purpuric eruptions develop in patients treated with TNFα inhibitors, PPD and vasculitis should be differentiated. Thus, patients are not exposed to unnecessary evaluations and treatments.

[Overview and therapy update Crohn's disease].

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. The pathophysiology of CD includes a disrupted interplay of intestinal bacteria, the intestinal immune system and the intestinal surface in genetically susceptible individuals, which remains incompletely understood. Conventional therapies include steroids, but numerous advanced therapies are also available. Three tumor necrosis factor (TNF) inhibitors (infliximab, adalimumab and certolizumab pegol (Switzerland)) have been approved for MC. Additional treatment options include the interleukin (IL)-12/23 inhibitors ustekinumab and the integrin inhibitors vedolizumab. With risankizumab, a first selective IL-23 inhibitor for CD has been approved by the EMA in 2022. Moreover, the Janus kinase-1 inhibitor upadacitinib has been available for the treatment of CD in the EU since 2023. For localized CD, elective surgical resection also remains a valid option with good long-term outcomes. Perianal and fistulizing CD are difficult to treat and require a close interdisciplinary collaboration between gastroenterologists and colorectal surgeons. Surgical fistula treatment with curative intent should only be performed in well-controlled CD. The recent increase in therapeutic options in CD is encouraging, since more safe and effective therapies are now available to patients. Nevertheless, CD remains an incurable disease and so far, for all existing treatments only a fraction of patients responds to the therapy. Therefore, the development of new therapies should continue.

Efficacy of certolizumab pegol across baseline rheumatoid factor subgroups in patients with rheumatoid arthritis: Post-hoc analysis of clinical trials.

AIM: Certolizumab pegol (CZP), an Fc-free, PEGylated tumor necrosis factor inhibitor (TNFi), has shown rapid and sustained reduction in signs and symptoms of rheumatoid arthritis (RA). Elevated rheumatoid factor (RF) level has been associated with RA disease progression and poorer TNFi response. We assessed the efficacy of CZP in patients with early and established RA across baseline RF levels. METHODS: This post-hoc analysis included data from 6 trials: C-OPERA (NCT01451203), pooled RAPID trials (RAPID-1 [NCT00152386], RAPID-2 [NCT00160602], J-RAPID [NCT00791999], RAPID-C [NCT02151851]), and EXXELERATE (NCT01500278). Patients who received CZP or placebo/comparator with methotrexate (MTX) were categorized by baseline RF quartiles. Efficacy was assessed with Disease Activity Score-28 erythrocyte sedimentation rate (DAS28-ESR). RESULTS: Overall, 316, 1537, and 908 patients were included in C-OPERA, pooled RAPID trials, and EXXELERATE, respectively. Patient demographics and baseline disease characteristics were similar between treatment groups and across RF quartiles. DAS28-ESR low disease activity (LDA) and remission (REM) rates were numerically higher in the CZP + MTX group than PBO + MTX group at weeks 12 and 24, across RF quartiles. LDA and REM rates in the CZP + MTX groups were comparable across RF quartiles at weeks 12 and 24. Mean DAS28-ESR decreased from week 0 to week 24 in the CZP + MTX groups, across RF quartiles. CONCLUSION: CZP showed steady efficacy across baseline RF quartiles in patients with early and established RA, over 24 weeks. CZP treatment may be considered in patients with RA irrespective of baseline RF levels and time from diagnosis.

Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Results from a 24-week post-marketing surveillance study.

OBJECTIVES: To report 24-week safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a post-marketing surveillance study. METHODS: Enrolled patients were newly receiving CZP. All adverse events (AEs) and adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes included: 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) and European Alliance of Associations for Rheumatology (EULAR) response. Missing data were imputed using the last observation carried forward. RESULTS: 3727 patients were enrolled; safety and effectiveness were evaluated in 3586 and 1794 patients, respectively. 24.9% of patients reported AEs (893/3586), 14.7% reported ADRs (528/3586), 8.3% (298/3586) reported serious AEs and 5.3% (190/3586) reported serious ADRs. Selected serious ADRs of interest: infections (110; 3.1%), tuberculosis (6; 0.2%), interstitial pneumonia (15; 0.4%), malignancy (8; 0.2%), and hepatic function disorder (7; 0.2%). No allergic reactions, autoimmune disease, cardiac failure, demyelinating diseases, or pancytopenia were reported. Mean DAS28-ESR reduced from 4.8 (baseline) to 3.4 (final evaluation). At final evaluation, 34.7% of patients achieved EULAR good response. CONCLUSIONS: These real-world safety and effectiveness results were consistent with previously reported data, with no new safety signals identified. Long-term, real-world CZP safety and effectiveness data are needed.

A Rare Case of Drug-induced Erectile Dysfunction with Adalimumab and Certolizumab Solved after Switch to Ustekinumab in a Crohn's Disease Patient.

BACKGROUND: Crohn Disease (CD) is an intestinal inflammatory condition characterized by a complex pathogenesis, with elevated levels of inflammatory cytokines. Adalimumab and certolizumab are two biologic drugs inhibiting TNF-α. OBJECTIVE: We report the first case of a probable relationship, according to Naranjo causality assessment score, between two consecutive treatments with TNF-α inhibitors and induced erectile dysfunction (ED), that disappeared after switching to another biologic drug (ustekinumab). CASE PRESENTATION: This case report describes a possible and important association of two TNF-α inhibitors (certolizumab and adalimumab) and ED in a male patient with CD, with resolution after switching to Ustekinumab (anti-interleukin 12 and 23 biologic drug). A 65 years old man experienced erectile dysfunction during treatment with an anti-TNF. The adverse effect disappeared after discontinuation of the drug. All necessary urologic exams were carried out. Adalimumab was replaced by certolizumab and sexual disfunction symptoms appeared again, improving typically at the end of treatment periods and getting worse with each new dose. RESULTS: Switching to ustekinumab lead to a resolution of the erectile dysfunction. CONCLUSION: We describe for the first time a sexual dysfunction possibly due to two similar anti TNF drugs and its resolution after the switch to another similar but different drug, highlighting the potential difference between biologic drugs.

Reported congenital malformations after exposure to non-tumour necrosis factor inhibitor biologics: A retrospective comparative study in EudraVigilance.

AIMS: To evaluate the number and nature of reported congenital malformations (CMs) after intrauterine exposure to non-tumour necrosis factor inhibitor biologics (non-TNFi biologics) compared to certolizumab pegol (CZP). METHODS: A retrospective comparative study was conducted in the EudraVigilance (EV) database. A safe biologic (CZP) was considered as the reference group. Odds ratios (ORs) for CMs were calculated for each non-TNFi biologic (including abatacept, anakinra, belimumab, ixekizumab, rituximab, secukinumab, tocilizumab, ustekinumab and vedolizumab), versus CZP (quantitative assessment). Then, CM patterns were reviewed in consultation with a clinical geneticist (qualitative assessment). RESULTS: ORs were not statistically significant except for belimumab and vedolizumab (similar in magnitude). Except for vedolizumab, no specific CM patterns were observed for the included non-TNFi biologics. Three cases of corpus callosum agenesis (CCA) were identified for vedolizumab (versus none in CZP and other investigated non-TNFi biologics). Two of the CCA cases were associated with other neurological CMs (one cerebral ventriculomegaly with microcephaly and one polymicrogyria). This may indicate that these CCAs are related to undiagnosed genetic alterations or are associated with the underlying maternal disease, although a definite relationship with vedolizumab exposure cannot be ruled out. CONCLUSION: No special safety signal was identified regarding the occurrence of CMs after exposure to abatacept (n = 64), anakinra (n = 20), belimumab (n = 93), ixekizumab (n = 29), rituximab (n = 57), secukinumab (n = 128), tocilizumab (n = 124) and ustekinumab (n = 215). Regarding observed CCAs in the vedolizumab group (n = 113), no firm conclusions can be made based on available information.

Certolizumab pegol for maintenance of medically induced remission in Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a disease with an impaired immune response characterized by chronic, relapsing-remitting, and progressive inflammation mainly affecting the gastrointestinal tract. Certolizumab pegol (CZP) is a biological agent that regulates the impaired immune response by controlling tumour necrosis factor-α (TNFα). However, the efficacy and safety of long-term administration of CZP for people with CD with inflammation under control are not well understood. OBJECTIVES: To assess the efficacy and safety of CZP for maintenance of remission in people with CD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, and conference abstracts from inception to 23 March 2022. We contacted pharmaceutical companies involved with the production of CZP for further relevant information. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing CZP with placebo in adults with CD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. The main outcomes were failure to maintain clinical remission at week 26, failure to maintain clinical response at week 26, and serious adverse events. We planned to perform meta-analyses including all available studies if similar enough for pooling to be appropriate and calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes. We analyzed the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) to indicate the magnitude of treatment effects. The same two review authors independently evaluated the risk of bias by using the Cochrane RoB 2 tool and evaluated the certainty of evidence using the GRADE framework. MAIN RESULTS: We identified one study meeting our prespecified eligibility criteria. The included study enrolled 428 adults with CD who responded to induction therapy with CZP 400 mg at weeks 0, 2, and 4. The study evaluated long-term efficacy and safety of CZP administered subcutaneously every four weeks compared with placebo. The proportion of participants who failed to maintain clinical remission at week 26 was 52.3% (113/216) in the CZP group compared to 71.7% (152/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical remission at week 26 (RR 0.73, 95% CI 0.63 to 0.85). The NNTB was 5 (95% CI 4 to 9). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who failed to maintain clinical response at week 26 was 37.5% (81/216) in the CZP group compared to 64.2% (136/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical response at week 26 (RR 0.58, 95% CI 0.48 to 0.71). The NNTB was 4 (95% CI 3 to 5). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who developed serious adverse events was 5.6% (12/216) in the CZP group compared to 6.6% (14/212) in the placebo group. Treatment of CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment (RR 0.84, 95% CI 0.40 to 1.78). The NNTB was 95 (95% CI NNTH 19 to NNTB 25). We evaluated the risk of bias for this outcome as low. We evaluated the certainty of evidence as low due to the low number of events occurred and the CIs were not sufficiently narrow. AUTHORS' CONCLUSIONS: CZP probably results in a large reduction in failure to maintain clinical remission and response at week 26 in people with CD. The evidence suggests that CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment. However, the current studies are limited to 26 weeks of follow-up and only included adults. Therefore, these conclusions cannot be used to guide longer term treatment or for treatment in children at present.

Long-term safety and clinical outcomes of certolizumab pegol treatment in patients with active non-radiographic axial spondyloarthritis: 3-year results from the phase 3 C-axSpAnd study.

BACKGROUND: 52-week results from C-axSpAnd demonstrated the safety and efficacy of certolizumab pegol (CZP) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammation (sacroiliitis on MRI and/or elevated C-reactive protein levels). Long-term safety and clinical outcomes, including MRI assessments, are evaluated up to 3 years for CZP-treated patients with nr-axSpA. METHODS: C-axSpAnd was a phase 3 study comprising a 1-year double-blind, placebo-controlled period and 2-year open-label safety follow-up extension (SFE). At baseline, 317 patients were randomised 1:1 to placebo or CZP 200 mg every 2 weeks. Patients completing the double-blind phase who enrolled into the SFE received open-label CZP for an additional 104 weeks. Long-term safety and clinical outcomes are reported to Week 156. Continuous outcomes are presented as observed case (OC) and dichotomous outcomes as OC and with non-responder imputation. RESULTS: 243/317 (76.7%) patients entered the SFE, during which 149 (61.3%) experienced ≥1 treatment-emergent adverse event (TEAE); 15 (3.3/100 patient-years) experienced serious TEAEs. Continuous outcome scores (including Ankylosing Spondylitis Disease Activity Score [ASDAS]: 1.8; Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]: 2.7) at Week 52 were maintained at Week 156 (ASDAS: 1.8; BASDAI: 2.6) for the initial CZP-randomised group. Mean SPARCC MRI sacroiliac joint inflammation scores for these patients decreased at Week 52 (baseline: 7.6; Week 52: 1.7), remaining low at Week 156 (2.4). CONCLUSIONS: CZP treatment was well tolerated up to 3 years, with no new safety signals versus previous reports. Clinical outcomes achieved after 1 year were sustained to 3 years. TRIAL REGISTRATION NUMBER: NCT02552212.

The Risk of Adverse Effects of TNF-α Inhibitors in Patients With Rheumatoid Arthritis: A Network Meta-Analysis.

OBJECTIVES: To evaluate the safety of each anti-TNF therapy for patients with rheumatoid arthritis (RA) and then make the best choice in clinical practice. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library. The deadline for retrieval is August 2021. The ORs, Confidence Intervals (CIs), and p values were calculated by STATA.16.0 software for assessment. RESULT: 72 RCTs involving 28332 subjects were included. AEs were more common with adalimumab combined disease-modifying anti-rheumatic drugs (DMARDs) compared with placebo (OR = 1.60, 95% CI: 1.06, 2.42), DMARDs (1.28, 95% CI: 1.08, 1.52), etanercept combined DMARDs (1.32, 95% CI: 1.03, 1.67); certolizumab combined DMARDs compared with placebo (1.63, 95% CI: 1.07, 2.46), DMARDs (1.30, 95% CI: 1.10, 1.54), etanercept combined DMARDs (1.34, 95% CI: 1.05, 1.70). In SAEs, comparisons between treatments showed adalimumab (0.20, 95% CI: 0.07, 0.59), etanercept combined DMARDs (0.39, 95% CI: 0.15, 0.96), golimumab (0.19, 95% CI: 0.05, 0.77), infliximab (0.15, 95% CI: 0.03,0.71) decreased the risk of SAEs compared with golimumab combined DMARDs. In infections, comparisons between treatments showed adalimumab combined DMARDs (0.59, 95% CI: 0.37, 0.95), etanercept (0.49, 95% CI: 0.28, 0.88), etanercept combined DMARDs (0.56, 95% CI: 0.35, 0.91), golimumab combined DMARDs (0.51, 95% CI: 0.31, 0.83) decreased the risk of infections compared with infliximab combined DMARDs. No evidence indicated that the use of TNF-α inhibitors influenced the risk of serious infections, malignant tumors. CONCLUSION: In conclusion, we regard etanercept monotherapy as the optimal choice for RA patients in clinical practice when the efficacy is similar. Conversely, certolizumab + DMARDs therapy is not recommended. SYSTEMATIC REVIEW REGISTRATION: identifier PROSPERO CRD42021276176.

Certolizumab-induced lichenoid eruption in a patient with rheumatoid arthritis.

Certolizumab is a monoclonal antibody against tumour necrosis factor-alpha (TNF-α) commonly used in rheumatologic conditions such as rheumatoid arthritis. Skin rashes are an uncommon side effect with few cases of lichenoid drug eruption reported in the literature. We describe a patient with rheumatoid arthritis who presented 6 weeks after initiating certolizumab pegol. Physical examination showed pink-to-violaceous papules on her upper and lower extremities. Biopsy confirmed a lichenoid drug eruption. The medication was discontinued and she was treated with topical steroids and a calcineurin inhibitor, with resolution of her lesions. Clinicians should be cognizant of such adverse reactions to TNF-α inhibitors and keep drug-induced lichenoid eruptions on the differential. Lichenoid eruptions induced by certolizumab pegol may affect the skin and/or mucous membranes. While most cases occur within weeks to months of starting therapy, eruptions may occur years after treatment initiation, underscoring the importance of a thorough review of medications.

Three-year efficacy and safety of certolizumab pegol for the treatment of plaque psoriasis: results from the randomized phase 3 CIMPACT trial.

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumor necrosis factor biologic. OBJECTIVES: To report 3-year outcomes from the CIMPACT (NCT02346240) phase 3, CZP in moderate to severe plaque psoriasis, randomized controlled trial. METHODS: Adults were randomized 3:3:3:1 to CZP 200 mg every other week (Q2W), CZP 400 mg Q2W, etanercept biweekly or placebo. At Week 16, CZP- and etanercept-treated PASI 75 responders were re-randomized to CZP 200 mg Q2W, CZP 400 mg Q4W, CZP 400 mg Q2W or placebo for maintenance treatment; PASI 75 non-responders entered an open-label escape CZP 400 mg Q2W arm. Patients entering the open-label extension (OLE; Weeks 48-144) from blinded treatment received CZP 200 mg Q2W. RESULTS: Double-blinded results have been reported previously. 261 patients received 200 mg Q2W upon OLE entry. PASI 75 response was maintained in patients continuing 200 mg Q2W treatment through Weeks 16-144 (Week 144: 96.2%). In patients dosed down at Week 48 (double-blinded 400 mg to 200 mg Q2W), PASI 75 decreased (Week 48: 98.7%; Week 144: 85.9%). In patients who received placebo through Weeks 16-48, PASI 75 response decreased (Week 48: 60.4%), then increased following Week 48 switch to 200 mg Q2W (Week 144: 95.1%). 48 and 36 patients initially randomized to 200 and 400 mg Q2W, respectively, were Week 16 PASI 75 non-responders and entered the escape arm; at Week 144, 71.8% and 78.2% achieved PASI 75. No new safety signals were identified. CONCLUSIONS: Response to CZP was durable over three years; no new safety signals were identified.

Certolizumab Pegol in Plaque Psoriasis: Considerations for Pregnancy.

Psoriasis is a chronic, immune-mediated skin condition which commonly affects women of childbearing age. Certolizumab pegol (CZP) is an anti-tumor necrosis factor-alpha (anti-TNFα) agent that has demonstrated long-term safety and efficacy in treating moderate-to-severe plaque psoriasis. Previously, there has been limited safety data surrounding its use in pregnancy. The objective of this article is to review pivotal clinical trial data for CZP and explore safety considerations for this agent in pregnancy. This review demonstrates that CZP offers a safe and effective treatment option for women during childbearing years based on pharmacokinetics and available safety data. The observed occurrence of major congenital malformations and miscarriages appears to be no greater than the background occurrence of those in the general population, and risks to the mother are minimal based on its known safety profile. The use of CZP for treatment of plaque psoriasis should be considered and discussed with patients considering childbearing or whom are currently pregnant or breastfeeding.

Certolizumab pegol in the treatment of psoriasis: Real-life data.

Certolizumab pegol (CZP), the only Fc-free, PEGylated anti-tumor necrosis factor biologic agent. This study aims to investigate the effect and safety of CZP in moderate-to-severe chronic plaque psoriasis. We performed a retrospective observational analysis of the moderate-to-severe psoriasis patients under ceratolizumab pegol therapy. Primer endpoints were efficacy of CZP, defined as statistically significant improvement of Psoriasis Area and Severity Index (PASI), Physician's Global Assessment (PGA), and clinical Disease Activity index for Psoriatic Arthritis (cDAPSA) in the 24 week of therapy. Secondary endpoints were safety of CZP especially during COVID-19 pandemic. Fifty-six moderate-to-severe psoriasis patients treated with CZP were evaluated retrospectively. We observed a rapid and significant reduction of PASI, PGA, and cDAPSA scores in W4. After loading dose, we observed loss of clinical efficacy of CZP in eight patients and optimized therapy by increasing the dosing of CZP. Dose escalation of CZP permitted the achievement and long-term maintenance of clinical improvement in these patients. We compare the clinical efficacy of CZP between naive and patients who has been treated with other biologic agents. There were no statistical differences in efficacy between these two groups. No side effects were observed during CZP treatment. There were no cases of death from COVID-related disease in our study population or patients hospitalized for COVID-19 related disease. Our results demonstrate that CZP is an effective and safe therapeutic option for patients with moderate-to-severe chronic plaque psoriasis.

Three-year clinical outcomes in patients with rheumatoid arthritis treated with certolizumab pegol: results from the observational ECLAIR study.

OBJECTIVES: To describe the long-term effectiveness and safety of certolizumab pegol in patients with moderate-to-severe rheumatoid arthritis (RA) in a real-world setting in France. METHODS: ECLAIR was a 3-year longitudinal, prospective, observational, multicentre study. The primary objective was to describe the EULAR response after 1 year of certolizumab pegol treatment. Other endpoints included DAS28, clinical disease activity index, health assessment questionnaire disability index, fatigue assessment scale, patient's assessment of arthritis pain, patient and physician global assessments of disease activity, patient quality of life, and long-term safety. RESULTS: A total of 792 patients were enrolled, of whom 776 comprised the safety set, and 733 the full analysis set. In the full analysis set, 559, 469 and 430 patients had a 12-, 24- and 36-month visit, respectively. This included 378, 296 and 246 patients still receiving certolizumab pegol at these visits. The percentage of EULAR responders was 75.3% (305/405 patients with an available EULAR response) at 12, 76.5% (261/341) at 24, and 79.6% (226/284) at 36 months. Among those still receiving certolizumab pegol, the percentage of EULAR responders was 81.7% (237/290) at 12, 81.1% (185/228) at 24, and 87.3% (158/181) at 36 months. Sustained improvements were observed in other effectiveness outcomes. Overall, 45.1% (350/776) of patients experienced 776 adverse drug reactions. No new safety signals were identified. CONCLUSIONS: This is the first prospective, observational study of an anti-TNF treatment in France. The results confirm the effectiveness and safety profile of certolizumab pegol treatment in patients with RA in a real-world setting.

Efficacy of certolizumab pegol in naïve versus multi-treated patients affected by psoriatic arthritis.

BACKGROUND: The efficacy and safety of certolizumab pegol over 52 weeks was compared in two groups of patients: Group 1 comprised patients naïve to biologic treatments; Group 2 comprised patients previously treated with one or more antitumor necrosis factor (TNF)-α and/or anti-interleukin (IL) agents. METHODS: We reported results in 50 patients affected by both mild psoriasis (PsO) and psoriatic arthritis (PsA). Primary endpoint was a reduction from baseline at week 52 of Disease Activity Score (DAS44-ESR) in both groups of patients. Secondary endpoints were a reduction from baseline at week 52 of Psoriasis Area Severity Index (PASI), Visual Analog Scale for Pain (PAIN VAS), ESR, CRP, and Dermatology Life Quality Index (DLQI). RESULTS: We observed a statistically significant improvement of both cutaneous and rheumatic disease in all patients, with a consistent reduction of DAS44-ESR, PASI, and PAIN VAS from baseline to week 52. DAS44-ESR decreased from 3.9 at BL to 1.5 at W52 (Group 1), and from 3.8 to 1.7 at W52 (Group 2). Mean PASI Score decreased from 3.2 at baseline (BL) to 0.4 at W52 (Group 1), and from 5.4 to 0.7 at W52 (Group 2). Mean PAIN-VAS decreased from a value of 73.5 at BL to 2.5 at W52 (Group 1), and from a value of 62.4 at BL to 9.2 at W52 (Group 2). We also found a reduction in ESR, CRP and DLQI values for each time point. CONCLUSIONS: Our results confirm that CZP can be administered safely and effectively to treat both psoriasis and psoriatic arthritis irrespective of previous treatments with biologic agents.

Efficacy and safety of certolizumab pegol in pregnant women with uveitis. Recommendations on the management with immunosuppressive and biologic therapies in uveitis during pregnancy.

OBJECTIVES: Clinicians often face the challenge of providing effective and safe therapy for pregnant women with uveitis. Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer. In this study we assessed the efficacy of CZP in pregnant women with uveitis. We also provided information on outcomes of pregnant women and neonates exposed to CZP. METHODS: We carried out a multicentre study of women with uveitis who received CZP during pregnancy and their neonates. The main visual outcomes were visual acuity (VA), intraocular inflammation and corticosteroid-sparing effect. Pregnancy outcomes, maternal and neonatal infections and congenital malformations were also assessed. RESULTS: We studied 14 women (23 affected eyes); mean age of 34.3±5.5 years. The underlying diseases were spondyloarthritis (n=7), idiopathic (n=2), and Vogt-Koyanagi-Harada, rheumatoid arthritis, juvenile idiopathic arthritis, punctate inner choroidopathy and Behçet's disease (1 each). The patterns of ocular involvement were anterior (n=10), posterior (n=2), intermediate (n=1), panuveitis (n=1). Cystoid macular oedema was present in one patient (1 eye). Uveitis was bilateral in nine cases and chronic in seven patients. CZP was started before getting pregnant in ten patients and after conceiving in four. All patients achieved or maintained ocular remission throughout pregnancy. Fifteen healthy infants were born. Only one woman presented a mild infection during pregnancy. Neither infections nor malformations were observed in neonates after a follow-up of 6 months. Six infants were breastfed and all of them received scheduled vaccinations without complications. CONCLUSIONS: Certolizumab pegol is effective and safe in women with uveitis during pregnancy.