Long term treatment of psoriatic arthritis with infliximab (original) (raw)
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British Journal of Dermatology, 2007
Background Infliximab, an antitumour necrosis factor-a chimeric monoclonal antibody, is effective for the treatment of severe psoriasis. While the induction of antinuclear antibodies (ANA) and antidouble-stranded-DNA antibodies (anti-dsDNA-ab) is frequently observed in patients with rheumatoid arthritis and Crohn disease receiving infliximab, the incidence of induced biological and clinical autoimmunity remains unknown in the context of psoriasis. Objectives To investigate biological and clinical signs of autoimmunity in 28 patients receiving infliximab for severe, recalcitrant forms of psoriasis, and the clinical response to treatment. Methods Twenty-eight patients, 15 men and 13 women (median age 39AE4 years) with psoriasis refractory to three or more systemic treatments were included. Twenty presented with plaque-type psoriasis [median Psoriasis Area and Severity Index (PASI) score 25AE9; range 7AE2-48], five with psoriatic erythroderma (median PASI score 54; range 48-72) and three with generalized pustular psoriasis (GPP). Psoriatic arthritis was present in 13 patients (46AE4%). Infliximab 5 mg kg )1 was given at week (W) 0, W2, W6 and every 8 weeks thereafter. Clinical data were assessed at baseline and before each infusion. Detection of ANA and of IgM and IgG anti-dsDNA-ab were performed at baseline and at W22 by immunofluorescence and enzyme-linked immunosorbent assay, respectively. Results The mean number of infliximab infusions was 5AE5 (range 2-15). Among patients with plaque-type and erythrodermic psoriasis, 17 of 25 (68%) and three of five reached a PASI improvement of 75% or more, respectively, while rapid improvement of clinical and biological signs was observed in all three patients with GPP. The prevalence of positive detection of ANA raised from 12% at baseline to 72% at W22 (P ¼ 0AE0001), an increase which was also observed for IgM anti-dsDNA-ab (68% vs. 0%, P < 0AE0001), while no significant change was observed for the IgG isotype (16% vs. 0%, P ¼ 0AE125). Three patients developed nonerosive polyarthritis, without any other criteria for systemic lupus. Conclusions The incidence of biological autoimmunity is high in patients with refractory psoriasis receiving infliximab. The concomitant onset of polyarthritis in three cases raises the need to investigate the incidence of autoimmune manifestations in psoriatic patients receiving infliximab in further large-scale studies.
Infliximab-Induced Lupus: A Case Report
GE - Portuguese Journal of Gastroenterology, 2016
after starting infliximab (November 2013), the patient complained of inflammatory symmetrical polyarthralgia (knee, shoulder, elbow, and wrist) without synovitis, which started every week before the administration of infliximab. Resolution of symptoms was observed after each infliximab infusion. In July 2014, the autoantibody re-evaluation showed positive ANA with a homogeneous pattern with a titer of 1: 640, weak positive anti-dsDNA (30.2), and positive anti-histone with C3 decreased (80.3). She was then diagnosed with lupus induced by infliximab and initiated hydroxychloroquine 400 mg. Infliximab was suspended. On re-evaluation, the erythrocyte sedimentation rate was 25 mm/h (1st hour), C-reactive protein 0.5 mg/dL (previously erythrocyte sedimentation rate 15 mm/h and C-reactive protein 1.2 mg/dL), and endoscopically, the mucosa was scarred, with some atrophy and scarce mucus in the lower rectum. About 10 months after discontinuation of infliximab, repeated autoantibodies proved all negative, keeping only low C3 (87). The patient also reported complete resolution of the arthralgia.
Arthritis and Rheumatism, 2005
ObjectiveTo investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA).To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA).MethodsOne hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score.One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score.ResultsThe proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of ≥2.5 at baseline, 68% of infliximab-treated patients achieved improvement of ≥75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups.The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of ≥2.5 at baseline, 68% of infliximab-treated patients achieved improvement of ≥75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups.ConclusionTherapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.
Infliximab in Psoriasis and Psoriatic Arthritis
BioDrugs, 2013
Psoriasis is a chronic inflammatory disorder of the skin and joints. Although rarely life threatening, psoriasis can significantly impair quality of life (QOL) and cause considerable physical and psychological distress. Between 6 and 42% of patients with psoriasis develop psoriatic arthritis, which is characterized by stiffness, pain, swelling and tenderness of the joints. Nail psoriasis is highly prevalent in both plaque-type psoriasis and psoriatic arthritis and is found in approximately 50% of patients with psoriasis and in 80% of patients with psoriatic arthritis. Infliximab, a chimeric human-murine monoclonal antibody directed against tumour necrosis factor a, is approved in the USA and EU for the treatment of plaque psoriasis and psoriatic arthritis at a recommended dosage of 5 mg kg administered by intravenous infusion at 0, 2 and 6 weeks, then every 8 weeks thereafter. The EXPRESS and EXPRESS II trials demonstrated that infliximab is efficacious as induction and maintenance therapy in the treatment of moderate to severe plaque psoriasis and also improved health-related QOL. Infliximab is also efficacious in the treatment of psoriatic arthritis, as shown in the IMPACT and IMPACT II studies. Infliximab is generally well tolerated, with a similar adverse event profile in both psoriasis and psoriatic arthritis. The use of infliximab in three case reports is presented. The patients are similar to those normally seen by clinicians, and include a male patient with plaque psoriasis and a history of severe psoriatic arthritis who was corticosteroid dependent and in whom other systemic treatments were not effective or were not able to be used. This patient showed a rapid response to infliximab with no skin lesions or arthritis after 7 weeks' treatment. Infliximab was also safe and effective in the treatment of a female patient with plaque and nail psoriasis and a history of psoriatic arthritis. Importantly, this case report supports the efficacy of infliximab in psoriatic nail disease in the context of severe skin and joint involvement. Case 3 describes a young male patient with moderate plaque-type psoriasis associated with severe nail involvement and early signs of psoriatic arthritis. Treatment with infliximab improved nail psoriasis and appears to be an effective biological treatment for nail psoriasis. Importantly, ultrasound was able to diagnose joint involvement, as seen from the proliferative synovitis in the distal interphalangeal joint and mild enthesitis, despite there being no clinical evidence of psoriatic arthritis. This case report highlights the importance of early screening. If such abnormalities are detected early on in the course of psoriasis, clinicians may be able to predict which patients are more likely to develop psoriatic arthritis, and therefore offer effective and long-term treatment that may reduce the disability and impairment of daily activities that can be associated with psoriatic arthritis.
Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial
Annals of the Rheumatic Diseases, 2005
Objectives: To evaluate further in a phase III, double blind trial the efficacy of infliximab in patients with active psoriatic arthritis (PsA), as observed in the smaller IMPACT trial. Methods: 200 patients with active PsA unresponsive to previous treatment were randomised to infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, 14, and 22. Patients with inadequate response entered early escape at week 16. The primary measure of clinical response was ACR20. Other measures included Psoriatic Arthritis Response Criteria (PsARC), Psoriasis Area and Severity Index (PASI), and dactylitis and enthesopathy assessments. Results: At week 14, 58% of patients receiving infliximab and 11% of those receiving placebo achieved an ACR20 response and 77% of infliximab patients and 27% of placebo patients achieved PsARC (both p,0.001). Among the 85% of patients with at least 3% body surface area psoriasis involvement at baseline, 53/83 (64%) patients receiving infliximab had at least 75% improvement in PASI compared with 2/87 (2%) patients receiving placebo at week 14 (p,0.001). These therapeutic effects were maintained through the last evaluation (week 24). Fewer infliximab patients than placebo patients had dactylitis at week 14 (18% v 30%; p = 0.025) and week 24 (12% v 34%; p,0.001). Fewer infliximab patients (22%) than placebo patients (34%) had active enthesopathy at week 14 (p = 0.016); corresponding figures at week 24 were 20% and 37% (p = 0.002). Infliximab was generally well tolerated, with a similar incidence of adverse events in each group. Conclusions: Infliximab 5 mg/kg through 24 weeks significantly improved active PsA, including dactylitis and enthesopathy, and associated psoriasis.
Antinuclear Antibodies in Patients with Psoriatic Arthritis Treated or Not with Biologics
PLOS ONE, 2015
Background With the emergence of biotherapies, accurate diagnosis in early arthritis is needed. At this time, there is no biological marker of psoriatic arthritis. Objective To test whether antinuclear antibodies (ANA) can be used as a diagnostic tool in psoriatic arthritis (PsA), we evaluated the prevalence of ANA in biologic-naïve PsA patients and in healthy blood donors. Methods 232 patients from the Rheumatology department, St Marguerite's Hospital, Marseilles, who fulfilled the CASPAR criteria for PsA, underwent clinical and laboratory investigations. Antinuclear antibodies (ANA), anti-extractable nuclear antigen antibodies (ENA), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) were assayed. Ninety-one healthy blood donors were also tested. Results Detection of ANA by indirect immunofluorescence was significantly more frequent in sera from PsA patients than those from controls at serum dilution of 1:100 (57% compared with 40%, Odds Ratio (OR) 1.98 (1.2-3.4) p<0.02) and 1:160 (52% compared with 24%, OR 3,7 (1.9-7.2) p<0.001). No patients had lupus specific autoantibodies, 15 % had RF (34/232), and 1.7 % had ACPA (4/232).
Efficacy of infliximab in resistant psoriatic arthritis
Arthritis & Rheumatism, 2003
Objective. To evaluate the efficacy and safety of the anti-tumor necrosis factor ␣ monoclonal antibody infliximab in the treatment of active psoriatic arthritis (PsA) resistant to previous symptom modifying antirheumatic drugs. Methods. Sixteen patients with peripheral active PsA with at least 6 months of methotrexate (MTX) therapy at a stable dosage were treated with infliximab administered at a dosage of 3 mg/kg at 0, 2, 6, 14, 22, and 30 weeks while continuing to receive MTX. Intake of nonsteroidal antiinflammatory drugs and corticosteroids was stable during the study period. Standard clinical assessments, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were determined at baseline and at weeks 2, 6, 14, 22, and 30.
Infliximab induced chilblain lupus in a patient with rheumatoid arthritis
The Journal of rheumatology, 2005
We read with interest of the experience of Richette and colleagues in the use of infliximab in rheumatoid arthritis (RA) 1 , in which they describe the development of necrotizing vasculitis-associated sensory neuropathy in one patient and the deterioration of rheumatoid vasculitis-associated mononeuritis multiplex in another. This contrasts with our own recent experience of a patient with rheumatoid vasculitis who developed a mononeuritis of the left common peroneal nerve with foot-drop, resistant to 6 infusions of cyclophosphamide and high dose oral steroid, but resolving entirely after 6 doses of infliximab. The patient was a 52-year-old woman with a 20 year history of erosive seropositive RA, which had been resistant to treatment with a range of disease modifying antirheumatic drugs over the years, including methotrexate, myocrisine, and D-penicillamine; she was then maintained on leflunomide 10 mg and prednisolone 20 mg daily. Her drug therapy had been unchanged for over a year, except for a gradual increase in her dose of steroid. She had a history of rheumatoid vasculitis, treated successfully with intravenous cyclophosphamide, but leaving her with a peripheral sensory neuropathy in both feet, with reduced sensation from mid-shin distally. She presented 4 months before commencing infliximab therapy with left-side foot-drop that had developed over a few days. On examination, there was complete loss of power on dorsiflexion of the left foot. Nerve conduction studies revealed marked distal delay in the left common peroneal nerve (6.2 ms) and undetectable motor response. The rest of the neurological examination was unchanged. She received 6 infusions of 500 mg cyclophosphamide over 12 weeks, with 40 mg prednisolone daily and cotrimoxazole prophylaxis, without any improvement in her foot-drop. Four months after her presentation she commenced infliximab (3 mg/kg), stopped leflunomide, and restarted methotrexate at a dose of 7.5 mg/week. The steroid dose was initially unchanged, but was gradually reduced to 5 mg daily once she reported significant clinical improvement in pain and stiffness with infliximab infusions. After the third infliximab infusion, there was a gradual return of left ankle dorsiflexion, and after the sixth infusion, power had returned to normal. Despite the negative experience of Richette and colleagues, and other reports of the development of optic neuritis with infliximab treatment in RA 2 , we suggest that the drug can offer benefits to at least some patients with rheumatoid vasculitis-associated mononeuritis.
Cytokine profiles during infliximab monotherapy in psoriatic arthritis
British Journal of Dermatology, 2005
Background Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)-a antagonists such as infliximab and etanercept are the most promising as TNF is considered to be essential in driving cytokine cascade at sites of cutaneous and synovial inflammation in this disease. Objectives To evaluate the time-related response of serum cytokine release during infliximab monotherapy and assess serum cytokine levels in order to provide a fast, minimally invasive tool to monitor and ⁄or predict efficacy of anti-TNF-a therapy. Methods Twenty patients affected by PsA with Psoriasis Area and Severity Index (PASI) score between 0AE4 and 42AE8 were treated with infliximab for 30-42 weeks. The assessment of arthritis severity was performed using the American College of Rheumatology (ACR) criteria and ultrasonography evaluation. The treatment schedule consisted of infliximab (5 mg kg)1 intravenously) at 0, 2 and 6 weeks and every 12 weeks on an individual basis determined by therapeutic results and adverse events reported. At baseline and before every infusion blood samples were taken to assess serum cytokine levels [TNF-a, interleukin (IL-6), E-selectin, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase (MMP-2)]. Results Eighteen of 20 psoriatic patients achieved > 50% improvement and 14 of 20 patients attained > 75% improvement in the PASI score at 10 weeks. All arthritic patients achieved > 50% improvement (ACR-50) and 16 of 20 patients attained > 75% improvement (ACR-75) at 10 weeks. TNF-a did not decrease immediately during the first part of the study. A significant decrease was detected at week 12 (P < 0AE01). In contrast, IL-6, VEGF, FGF and E-selectin showed significant decreases after early infliximab infusions. PASI was not correlated with TNF-a in the serum but was significantly correlated with FGF, VEGF and MMP-2. Treatment was well tolerated and there were no significant adverse events in most patients, other than an urticarial reaction and an autoimmune hepatitis. Conclusions Monotherapy with infliximab has to be considered an efficacious and safe treatment for PsA in comparison with traditional disease-modifying antirheumatic drugs. The resolution of cutaneous and synovial symptoms is not related to TNF-a serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response. ANOVA P < 0AE01).