scholarly journals Golimumab for Rheumatoid Arthritis

2019 ◽  
Vol 8 (3) ◽  
pp. 387 ◽  
Author(s):  
Eleftherios Pelechas ◽  
Paraskevi Voulgari ◽  
Alexandros Drosos
Keyword(s):  
Rheumatoid Arthritis ◽  
Opportunistic Infections ◽  
Current Data ◽  
Genetically Engineered ◽  
Phase Iii ◽  
Real World Data ◽  
Standard Dosage ◽  
Subcutaneous Dose ◽  
Phase Iii Trials ◽  
Factor Α

Since the advent of infliximab for the treatment of rheumatoid arthritis (RA), new genetically-engineered molecules have appeared. This review aims to present the current data and body of evidence for golimumab (GLM). Safety, efficacy, tolerability and immunogenicity are all being investigated, not only through phase III trials (GO-BEFORE, GO-FORWARD, GO-AFTER, GO-MORE, GO-FURTHER, GO-NICE), but also through studies of real-world data. It seems that GLM in the subcutaneous form is an efficacious molecule with a good safety profile at the standard dosage scheme, but a 100 mg subcutaneous dose is associated with a higher risk of opportunistic infections, lymphoma and demyelination. Furthermore, when compared to other tumor necrosis factor-α molecules, it is non-inferior, and, at some points, such as when it comes to immunogenicity and persistence of the drug, it has a better profile. In summary, GLM is an effective, well-tolerated option for the treatment of RA, for both the clinician and patients who are seeking a convenient dosage scheme.

CVP alternating with fludarabine (CVP/F) chemotherapy prior to idiotype vaccination for follicular lymphoma (FL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8065-8065
Author(s):  
W. Z. Ai ◽  
F. J. Hsu ◽  
J. M. Timmerman ◽  
D. Czerwinski ◽  
B. Taidi ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Tumor Burden ◽  
Phase Iii ◽  
The Novel ◽  
Effective Immune Response ◽  
Best Response ◽  
Time To Treatment Failure ◽  
Phase Iii Trials ◽  
Idiotype Vaccine

8065 Background: Reducing the tumor burden prior to vaccination facilitates an effective immune response (IR) against the idiotype in FL. In this context, we evaluated the efficacy and toxicity of a novel cytoreductive regimen, CVP/F. Methods: Newly diagnosed, advanced stage FL patients (pt) were treated with CVP (cyclophosphamide 400 mg/m2 PO d1–5, vincristine 2 mg d 1, prednisone 100 mg/m2 d1–5) alternating with F (25 mg/m2 IV d1–5) every 21 days for 2 cycles beyond best response (maximum 8). Pt judged to be cytoreduced adequately were vaccinated monthly × 5 with idiotype protein made from their FL. Results: Among 34 enrolled pt, median age was 45 years (yr), and FLIPI scores were: 18% low, 71% intermediate and 12% high. 38% pt had grade 1 and 62% had grade 2 FL. There were no toxic deaths or opportunistic infections. With 233 cycles (117 CVP and 116 F) given to 33 evaluable pt, neutropenic fever occurred in 7 cycles (3%). 20 cycles (17%) of CVP and 29 cycles (25%) of F were dose reduced for leukopenia. 18 pt (53%) achieved a CR (16) or CRu (2), and 13 pt (38%) had a PR. 22 pt (65%) treated with CVP/F proceeded to vaccination; 10 additional pt (29%) were vaccinated after secondary chemotherapy was given for further cytoreduction. At median follow-up of 11.2 yr, 15-yr overall survival (OS) was 85%. Two of 5 deaths occurred without lymphoma progression. TTF (time to treatment failure = second treatment, relapse, death) at 11 yr was 38%. Anti-idiotype antibody and T cell IR were seen in 44% and 31% pt, respectively. There were no differences in TTF or OS according to IR. Conclusions: CVP/ F was effective in advanced FL, comparing favorably with our historical experience with CVP in terms of CR rate, proportion proceeding to vaccination, TTF and OS after vaccination. This favorable outcome may have been due to the novel alternating CVP/F cytoreductive regimen, idiotype vaccination or both. The idiotype vaccine is now being tested in phase III trials. The CVP/F regimen also warrants further evaluation. No significant financial relationships to disclose.

scholarly journals Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis

2015 ◽  
Vol 75 (6) ◽  
pp. 1133-1138 ◽  
Author(s):  
K L Winthrop ◽  
S-H Park ◽  
A Gul ◽  
M H Cardiel ◽  
J J Gomez-Reino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Viral Infections ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
A Priori ◽  
Clinical Trial Data ◽  
Incidence Rates ◽  
Phase Iii ◽  
High Background ◽  
Latent Tb

ObjectivesTo evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib.MethodsPhase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05).ResultsWe identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15–161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)).ConclusionsWithin the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.

scholarly journals Changing Perspectives in Diabetic Macular Oedema – Recognising and Understanding Chronic Diabetic Macular Oedema

2014 ◽  
Vol 08 (02) ◽  
pp. 145
Author(s):  
Usha Chakravarthy ◽  
Albert Augustin ◽  
Yit Yang ◽  
Michael Diestelhorst ◽  
Pascale Massin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Clinical Trial Data ◽  
Fluocinolone Acetonide ◽  
Phase Iii ◽  
Real World Data ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

The satellite symposium moderated by Usha Chakravarthy entitled ‘Changing Perspectives in Diabetic Macular Oedema: Recognising and Understanding Chronic Diabetic Macular Oedema’ was convened at the 2014 EURETINA Congress. The symposium discussed the multiple processes involved in chronic diabetic macular oedema (DMO) and the use of medications, in particular, corticosteroids in its management. As DMO progresses, inflammatory cytokines are up-regulated relative to vascular endothelial growth factor (VEGF) and these promote various pathways that ultimately result in retinal damage in chronic disease. It is important therefore that treatments for chronic DMO address this altered inflammatory cytokine profile to effectively manage the condition. ILUVIEN®, a 190 μg intravitreal implant in applicator (with a daily release rate of 0.2 μg/day fluocinolone acetonide [FAc] implant) is a second-line therapy indicated for the treatment of chronic DMO. This implant has been shown in phase III trials to lead to marked improvements in visual acuity and in retinal thickness in patients with chronic DMO that were insufficiently response to first-line therapy (i.e. laser). Clinical trial data strongly support the use of the FAc implant in chronic DMO and now ‘real world’ data from its use in regular clinical practice are becoming available and interim results complement those reported in a clinical trial setting.

scholarly journals The role of upadacitinib in the treatment of moderate-to-severe active rheumatoid arthritis

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110476
Author(s):  
Ali Berkant Avci ◽  
Eugen Feist ◽  
Gerd Rüdiger Burmester
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Profile ◽  
High Efficiency ◽  
Janus Kinase ◽  
Phase Iii ◽  
Jak Inhibitors ◽  
Real World Data ◽  
Study Program ◽  
Once Daily ◽  
Randomized Controlled Studies

Despite recent promising developments in the treatment of rheumatoid arthritis (RA), a substantial proportion of patients still cannot achieve the treatment targets: low disease activity and remission. Janus kinase (JAK) inhibitors have the potential to fill this important gap with their high efficiency, rapid onset of action, and acceptable safety profile. The fact that the previously approved two JAK inhibitors, tofacitinib and baricitinib, inhibit more than one JAK molecule raised the question whether a safer profile can be possible by inhibiting fewer JAK molecules. Upadacitinib, a JAK 1 selective molecule developed in this context has been evaluated in the SELECT phase-III study program and demonstrated a high and rapid efficacy in monotherapy as well as in combination with csDMARDs both in csDMARD-naive RA patients and in patients refractory to csDMARD and bDMARD treatments. Upadacitinib 15 mg once daily displayed a similar safety profile except for increased creatine phosphokinase (CPK) levels and herpes zoster (HZ) risk compared to its active comparators methotrexate (MTX) and adalimumab. Most of the CPK elevations were asymptomatic, and most of the HZ cases were not serious. Along with the randomized-controlled studies and meta-analysis results, upadacitinib 15 mg once daily has a favorable efficacy/safety profile. Long-term extensions of current studies and real-world data will be important to fully appreciate its potential in the treatment of RA.

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