Refractory Psoriatic Arthritis Research Articles

Psoriatic arthritis: State of the art review

Psoriatic arthritis (PsA) accounts for around 20% of referrals to the early arthritis clinic and presents a significant diagnostic and management challenge. Early diagnosis is important to prevent long term functional disability and to ensure optimal management of arthritis and key comorbidities. From the rheumatologist’s perspective, the differential diagnosis includes rheumatoid arthritis, gout and other inflammatory arthritis’s. Once diagnosed, it is essential to assess the disease fully, including arthritis, enthesitis, dactylitis, skin/nail disease and axial involvement. Using this information, appropriate treatment can be planned using therapies that are effective at treating the relevant domains of disease. Despite poor data, traditional disease-modifying anti-rheumatic drugs are commonly used and have been effective in observational studies. Following tumour necrosis factor inhibitors, which have proven excellent efficacy in multiple domains of PsA, new biologics are available or in development and will improve treatment options for people with refractory PsA

Patients With Psoriatic Arthritis-Related Enthesitis and Persistence on Tofacitinib Under Real-World Conditions.

Information on the persistence of tofacitinib (TOF) in psoriatic arthritis (PsA) is scarce in real-world conditions. Our objective was to analyze the persistence and safety of TOF under these conditions. This was a single-center retrospective longitudinal observational study of all patients with PsA who received at least 1 dose of TOF. The main focus was on adverse events (AEs) and drug survival. Drug survival was analyzed by Kaplan-Meier curves and persistence explanatory factors by multivariate Cox regression models. The hazard ratio (HR) was used to measure association. Seventy-two patients were included, 54 women and 18 men, mean age 51.9 (SD 11.1) years, mean disease duration of 10.4 (SD 6.99) years. TOF was ≥ third line of therapy in > 70% of cases. The median survival was 13.0 (IQR 5.3-29.0) months. One-year retention rate was 52.7% (95% CI 42.4-65.6). TOF survival was not influenced by sex, disease duration, comorbidities, or line of treatment. Younger patients (HR 0.96, P = 0.01) and those with enthesitis (HR 0.37, P = 0.03) showed lower odds of drug discontinuation. The overall rate of AEs was 52.9 (95% CI 38.5-70.6)/100 person-years. Most AEs occurred during the first 6 months of exposure. In this real-world study, TOF showed a reasonably good retention rate in a PsA population that was mostly refractory to biologic and oral targeted synthetic disease-modifying antirheumatic drugs. There were no new causes for concern regarding safety. Patients with refractory PsA and enthesitis might be a specific target population for this drug.

Arthroscopic synovectomy versus intra-articular injection of corticosteroids for the management of refractory psoriatic or rheumatoid arthritis of the wrist: study protocol for a randomized controlled trial (ARCTIC trial)

BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up.MethodsThis protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0–100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups.DiscussionPersistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI.Trial registrationDutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020.ClinicalTrials.gov NCT04755127. Registered after the start of inclusion on 15 February 2021.

OA10 Sequential biologic usage in refractory psoriatic arthritis using ultrasound to detect psoriatic arthritis specific sub-clinical active disease

OA10 Sequential biologic usage in refractory psoriatic arthritis using ultrasound to detect psoriatic arthritis specific sub-clinical active disease

Familial Clustering of Juvenile Psoriatic Arthritis Associated with a Hemizygous FOXP3 Mutation.

We describe the clinical and genetic findings in four patients from a single family who presented with refractory psoriatic arthritis and were hemizygous in the forkhead box protein 3 (FOXP3) gene (c.1222G>A). We report four siblings with hemizygous mutation in the FOXP3 gene (c.1222G>A) who presented with type 1 diabetes mellitus and psoriatic arthritis poorly responsive to treatment. Our findings expand the phenotype spectrum of FOXP3 mutations. Immune dysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by mutations in FOXP3 gene, which lead to early onset of constellation of autoimmune manifestations. This report highlights the influence of immune dysregulation in juvenile arthritis.

Treatment With Tofacitinib in Refractory Psoriatic Arthritis: A National Multicenter Study of the First 87 Patients in Clinical Practice.

Tofacitinib (TOF) is the first Janus kinase (JAK) inhibitor approved for psoriatic arthritis (PsA). It has shown efficacy in patients refractory to anti-tumor necrosis factor-α in randomized controlled trials (RCTs). Our aim was to assess efficacy and safety of TOF in clinical practice. This was an observational, open-label multicenter study of PsA patients treated with TOF due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, corticosteroid dose-sparing effect, retention rate, and safety. A comparative study of clinical features between our cohort of patients and those from the OPAL Beyond trial was performed. There were 87 patients (28 women/59 men), with a mean age of 52.8 ± 11.4 years. All patients were refractory to biologic disease-modifying antirheumatic drugs (DMARDs) and/or to conventional synthetic DMARDs plus apremilast. TOF was started at 5 mg twice daily after a mean follow-up of 12.3 ± 9.3 years from PsA diagnosis. At first month, Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) decreased from median 4.8 (IQR 4.1-5.4) to 3.7 (IQR 2.8-4.7, P < 0.01), Disease Activity Index for Psoriatic Arthritis from median 28 (IQR 18.4-34.1) to 15.5 (IQR 10.1-25.7, P < 0.01), and C-reactive protein from median 1.9 (IQR 0.3-5.0) to 0.5 (IQR 0.1-2.2) mg/dL (P < 0.01). Also, TOF led to a significant reduction in prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOF retention rate at Month 6 was 77% (95% CI 65.2-86.3). Patients in clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL Beyond trial. Data from clinical practice confirm that TOF seems to be effective, rapid, and relatively safe in refractory PsA despite clinical differences with patients in RCTs.

EP24 Arthritis mutilans coexisting with three separate granulomatous diseases

Case report - IntroductionGranulomatous disorders are diverse in their aetiologies and presentations. We present an unusual case of severe psoriatic arthritis patient who subsequently developed multiple granulomatous diseases over time, granulomatous interstitial nephritis, granulomatous sarcoidosis with hilar lymphadenopathy and localised laryngeal granulomatous inflammation secondary to lambda type amyloidosis.Case report - Case description52-year-old gentleman with arthritis mutilans secondary to severe poorly controlled psoriatic arthritis was followed up in Rheumatology clinic. Earlier therapy with leflunomide and methotrexate provided inadequate control. Golimumab, despite giving a good response, was stopped in 2013 after 5 months of treatment due to acute kidney injury. Renal biopsy revealed granulomatous interstitial nephritis, thought to be Golimumab-induced based on the timing of usage and reversibility with discontinuation. He was then trialled on Ustekinumab and Secukinumab in 2016 and 2017 respectively with variable response.He also had a few-years history of voice change (high pitched) and sore throat which he attributed to recurrent colds. He denied dysphagia or breathlessness, and he did not have stridor. He has never smoked and only drank alcohol occasionally. ENT team noted white deposits on erythematous and thickened false vocal cords and posterior glottis with a thin web on microlaryngoscopy, which histologically proved to show granulomatous inflammation, potentially consisting of amyloid, although congo red stain was negative. On further investigation, including SAP scan, he was diagnosed with localised lambda type amyloid. Increasing throat pain and worsening dysphonia prompted change of management from conservative to a surgery at a specialist centre and an input from speech and language therapy team.During this time, consideration for Etanercept for his joint and skin disease was put on hold, pending further management of laryngeal amyloidosis. Furthermore, he presented to hospital with breathlessness in 2019, where his chest X-ray showed bulky right hilum and a follow-up CT chest revealed calcified right hilar and mediastinal lymphadenopathy, ground glass opacification and consolidation. Histology from hilar node was suggestive of sarcoidosis, with stain negative for amyloid.He underwent removal of false vocal cords for his symptomatic laryngeal amyloidosis. He continues to be followed up at the local Rheumatology, Dermatology and ENT team.Case report - DiscussionGranulomatous diseases have vast aetiologies, including infectious, immunological, neoplastic, and chemical-induced processes. The age at which they affect patients and tissue they involve also vary hugely. This is the first reported case of three seemingly unrelated granulomatous diseases occurring in a single patient with severe refractory psoriatic arthritis. Retrospective reassessment of the histology samples supported that these are three separate pathologies. It is very unusual for one patient to acquire multiple separate granulomatous diseases, which was why the diagnostic process of this patient was challenging. In this case, managing the original underlying psoriatic arthritis was particularly difficult due to interruptions of treatment for adverse drug effects and investigations and treatment of subsequent granulomatous diseases. The case also raises questions about possible currently unknown association between the pathologies.Case report - Key learning pointsKey points are the uniqueness of this case and that it highlighted the possibility of currently under-reported association between these three granulomatous conditions. As ever, a multidisciplinary approach to managing such a complex patient is important for the provision of good care.

Refractory Psoriatic Arthritis Responding to an Increased Dose of the Anti-TNF Monoclonal Antibody Adalimumab

Refractory Psoriatic Arthritis Responding to an Increased Dose of the Anti-TNF Monoclonal Antibody Adalimumab

Psoriatic arthritis: state of the art review

Psoriatic arthritis (PsA) accounts for around 20% of referrals to the early arthritis clinic and presents a significant diagnostic and management challenge. Early diagnosis is important to prevent long term functional disability and to ensure optimal management of arthritis and key comorbidities. From the rheumatologist's perspective, the differential diagnosis includes rheumatoid arthritis, gout and other inflammatory arthritides. Once diagnosed, it is essential to assess the disease fully, including arthritis, enthesitis, dactylitis, skin/nail disease and axial involvement. Using this information, appropriate treatment can be planned using therapies that are effective at treating the relevant domains of disease. Despite poor data, traditional disease-modifying anti-rheumatic drugs are commonly used and have been effective in observational studies. Following tumour necrosis factor inhibitors, which have proven excellent efficacy in multiple domains of PsA, new biologics are available or in development and will improve treatment options for people with refractory PsA.

Biologic medicine effective against refractory psoriatic arthritis

Biologic medicine effective against refractory psoriatic arthritis

Repository corticotropin injection in patients with refractory psoriatic arthritis: a case series.

PurposeAlthough numerous treatment options are available for patients with psoriatic arthritis (PsA), a need for effective and tolerable treatments remains for patients with refractory disease who have failed previous therapies and continue to experience tender and/or swollen joints, pain, and disease activity. Repository corticotropin injection (RCI) is believed to produce steroidogenic, steroid-independent, anti-inflammatory, and immunomodulatory effects in patients with rheumatic disorders, such as PsA. Limited literature exists on the use of RCI in patients with refractory PsA. The objective of this case series is to provide information on the clinical features of patients with refractory PsA and their response to RCI.PatientsNine patients treated with RCI for refractory PsA were retrospectively identified and included in the case series.ResultsAll the nine patients experienced at least transient improvements in their active skin and joint disease. In some patients, it was necessary to titrate the RCI to an appropriate dose. RCI was used in some patients to bridge with another PsA therapy, such as apremilast or certolizumab. RCI was well tolerated, but discontinued in three patients due to preexisting conditions (hypertension and hyperglycemia).ConclusionRCI may be a safe and effective option for patients with refractory PsA who failed therapy with multiple previous treatments.

Effectiveness and safety of adalimumab in treating moderate to severe psoriasis patients with psoriatic arthritis in Taiwan

Abstract Background/Objective The incidence of psoriasis vulgaris in Asians is estimated at 0.05–0.30%. Studies in North America and Europe demonstrated that adalimumab, a fully human monoclonal IgG1 antibody, is an efficacious treatment for psoriatic arthritis and chronic plaque psoriasis. The aim of this study was to evaluate the efficacy and safety of adalimumab in treating psoriatic arthritis (PsA) in patients who have moderate to severe psoriasis. Methods This was a retrospective study comprising 12 patients with chronic plaque psoriasis and psoriatic arthritis who were treated with adalimumab between October 2008 and February 2013. All had failed treatment with conventional systemic agents. Patients were started on adalimumab 40 mg every other week. Results At week 12, 3 of 12 patients (25%) achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75). With regard to PsA, at week 12, the improved Psoriatic Arthritis Response Criteria (PsARC) response was experienced by 75% (9 of 12) of the patients. Mean improvement in Dermatology Life Quality Index (DLQI) was 42%. Five of 12 patients (42%) experienced adverse events, which were generally mild. Conclusion Patients with refractory psoriatic arthritis appeared to be responsive to adalimumab. The achievement rate of PsARC in our study was comparable to the efficacy reported in previous literature. Detection of antinuclear antibodies was not associated with the responsiveness in this trial, nor did it influence the potential for adverse effects. Adalimumab as a monotherapy is generally effective and safe.

Efficacy of tocilizumab in a patient with refractory psoriatic arthritis

Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis and other possible systemic features. In the last years, PsA therapy has been revolutionized by the increasing knowledge in the pathogenetic mechanisms of the disease, involving dysfunction and oversecretion of multiple proinflammatory molecules, in particular tumor necrosis factor (TNF)-α. Hence, therapy of PsA refractory to disease-modifying antirheumatic drugs (DMARDs) relies mainly on the use of anti-TNF-α agents. However, since PsA can often be refractory also to these therapies, use of agents acting on other cytokines, such as interleukin (IL)-1 receptor targeted by anakinra, the IL-12/23 receptor by ustekinumab, the IL-17A by secukinumab, and the IL-6 receptor by tocilizumab, has been reported successfully. Herein we report a case of a refractory PsA patient successfully treated with the IL-6 receptor agent, tocilizumab. A review of the literature on the use of tocilizumab in PsA has been performed.

OP0164 Long-term TNF blockade induces joint repair in psoriatic arthritis

BackgroundPsoriatic arthritis (PsA) is characterized by a variety of radiographic changes which include both signs of joint destruction (joint space narrowing reflecting cartilage loss and bone erosions) and joint remodeling...

Etanercept Therapy for Psoriatic Arthritis in the Presence of Recurrent Non–Hodgkin Lymphoma

Tumor necrosis factor inhibitors (TNFi) have established efficacy in psoriasis and psoriatic arthritis; however, there are concerns regarding the risk of lymphoma with their use. Although current data suggest that this risk is not increased with TNFi treatment, there are no data on the risk of recurrence of previously treated lymphoma under TNFi therapy. Herein, we describe a 46-year-old man with recurrent non-Hodgkin lymphoma whose refractory psoriatic arthritis was effectively treated for 5.5 years with the TNFi etanercept, initiated just 7 months after achieving lymphoma remission, without recurrence of non-Hodgkin lymphoma. However, he subsequently died 6.5 years later of pancreatic adenocarcinoma.

Infliximab treatment in two Chinese patients with psoriatic arthritis

Psoriatic arthritis (PsA) is a rheumatoid factor (RF)-seronegative systemic inflammatory disorder associated with psoriasis. Current treatment for PsA in China is still focused on disease modifying anti-rheumatic drugs (DMARDs). In this paper, we report two Chinese patients with active longstanding PsA treated with infliximab, a human-mouse chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α). The results show that infliximab acted quickly and effectively in relieving peripheral and axial symptoms and refractory skin lesions, even in recombinant human TNF-α receptor (rhTNFR)-resistant case. The take-home message from our cases is that infliximab is a useful therapeutic option for refractory PsA, especially when a patient has a combination of psoriasis and psoriatic arthritis. Further local evidence and experience must be accumulated in order to make anti-TNF-α therapy more accessible to PsA patients in China.

Pesquisa de autoanticorpos em pacientes com artrite psoriásica sob terapia anti-TNFα

Anti-TNFα therapy has been effective in the treatment of patients with refractory psoriatic arthritis (PSA). However, the risk of developing autoantibodies commonly found in rheumatic diseases in PSA patients undergoing this therapy is not clear. To evaluate the induction of specific autoantibodies after anti-TNFα therapy in PSA patients. Serum samples from 23 PSA patients (women: 61%, age: 45.04 ± 12.68 years, polyarticular: 69.6%, disease duration: 13.3 ± 7.7 years, infliximab: 82.60%) obtained immediately before (baseline) and approximately one year after the introduction of anti-TNF therapy (last sample) (385 ± 131.45 days), were analyzed. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti-RNP and anti-Sm (passive hemagglutination); and anti-Ro/ SS-A and/or anti-La/SS-B, anti-chromatin, anti-histones, anti-citrullinated peptide (CCP), and anti-cardiolipin (ELISA) antibodies. At baseline, ANA was positive in 47.8% of patients, with predominance of homogeneous nuclear pattern (81.8%). All baseline serum samples were negative for rheumatoid factor and antibodies to cardiolipin, RNP, Sm, Ro/SS-A, anti-La/SS-B, anti-histone, and anti-dsDNA antibodies, while two patients were positive for anti-chromatin and one for anti-CCP. All ANA-positive samples at baseline, except for one, remained positive after the introduction of anti-TNF therapy; however, de novo ANA reactivity was observed in four originally negative patients (33.3%). Anti-Ro/SS-A, La/SS-B, cardiolipin, histones, dsDNA, and rheumatoid factor antibodies remained negative in all final serum samples tested, and anti-chromatin positivity was detected in three other patients. Our findings have shown that anti-TNF therapy induced ANA positivity in one third of PSA patients. The concomitant use of methotrexate did not interfere with this finding. In addition, all serum samples were systematically negative for specific rheumatic autoantibodies tested after the introduction of the biological treatment.

Syringotropic hypersensitivity reaction associated with infliximab and leflunomide combination therapy in a child with psoriatic arthritis

A 17-year-old boy with refractory psoriatic arthritis and alpha-1 antitrypsin deficiency who developed a syringotropic hypersensitivity reaction after 9 months of therapy with infliximab and leflunomide is described. Clinically, our patient showed a vasculitic-like skin rash involving both palms and soles, and histopathological examination revealed a syringotropic lymphocytic infiltrate directed toward the intra-epidermal portion of the eccrine ducts. These features have not been previously associated with infliximab or leflunomide therapy and represent a unique cutaneous hypersensitivity reaction that does not fit any known description of an immune-mediated hypersensitivity reaction.

Efficacy, effectiveness and safety of etanercept in monotherapy for refractory psoriatic arthritis: a 26-week observational study

To investigate the efficacy, effectiveness and safety of etanercept, a soluble tumour necrosis factor-alpha receptor, in a prospective observational cohort of patients with refractory psoriatic arthritis and polyarticular involvement. Twenty patients with psoriatic arthritis refractory to conventional anti-rheumatic drugs were treated with etanercept 25 mg subcutaneously twice a week for 26 weeks. Efficacy and safety were recorded at weeks 2, 6, 10, 16, 20 and 26. Effectiveness, defined as clinical remission, reduction of 50% in clinical parameters and concomitant NSAID use, was evaluated at 26 weeks. Etanercept therapy was efficacious in this cohort as 85% of the patients met the Psoriatic Arthritis Response Criterion at week 26. Effectiveness of etanercept for the individual patient was demonstrated, since at least 50% of the patients had a 90 and 85% improvement in swollen and tender joint count, respectively, and a 71% improvement in the Health Assessment Questionnaire at week 26. Four patients showed complete remission and NSAIDs were stopped in 10/15 patients. The most common adverse events were upper respiratory tract infections. Interestingly, in two patients psoriasis worsened during the study, unrelated to the course of arthritis. The administration of etanercept was interrupted in three patients for adverse events: one septic bursitis, one myocardial infarction and one tooth abscess. After resolution of the adverse events, etanercept was successfully reintroduced. Etanercept in monotherapy is efficacious, effective and safe in the majority of patients with refractory psoriatic arthritis.

Infliximab Therapy for Patients With Active and Refractory Spondyloarthropathies at the Dose of 3 mg/kg

: Infliximab at the dose of 5 mg/kg per infusion has been shown effective for the treatment of active spondyloarthropathies. It is not clear if the 5 mg/kg is required in most patients. : To evaluate the long-term efficacy and safety of infliximab at the lower dose of 3 mg/kg in patients with active and refractory ankylosing spondylitis (AS) and psoriatic arthritis (PsA). : Thirty patients were enrolled in a 78-week, single-center, prospective, open-label pilot study, including 16 patients with severe and active AS and 14 patients with active and refractory PsA. Infliximab (3 mg/kg, in combination with a stable dose of methotrexate was administered intravenously at 0, 2 and 6 weeks, and q8 weeks thereafter (schedule-A) and the improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; for AS patients) and Patient Global Assessment of Disease Activity (PDA; for PsA patients) was monitored at baseline and at every visit (primary variables). Patients who did not respond sufficiently at 14 weeks, as well as patients who relapsed at any time during follow-up, received infliximab every 4 weeks (treatment schedule-B). Three different statistical approaches (per-protocol, last observation carried forward and by intention-to-treat) were applied. : Ten patients discontinued treatment for various reasons, including 3 (10.0%) because of allergic reactions. Twenty patients (66.7%, 9 with AS and 11 with PsA) had completed 78 weeks of treatment (schedule-A, 11 patients; schedule-B, 9 patients). Of these patients, 18 (90.0%) showed optimal response (improvement >/=50%), including 13 (65.0%) with improvement >/=70%. ASsessments in AS (ASAS) 50% was attained by 7/9 AS patients (77.8%). At 78 weeks of treatment, statistically significant improvement of indices of disease activity, function and quality of life was observed by all statistical approaches applied. : Infliximab at 3 mg/kg every 8 weeks or, if needed, every 4 weeks appears to be an effective and rather safe treatment of patients with active and refractory AS and PsA after 78 weeks of treatment.