Comorbidities in Psoriatic Arthritis
Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi in Psoriasis and Psoriatic Arthritis, 2017
Given the concern for increased cardiovascular events with the use of NSAIDs, it is recommended that NSAIDs be used for the shortest time at the lowest possible dose in patients with PsA and known CVD or multiple known risk factors (Ogdie et al. 2015). Similarly, both NSAIDs and glucocorticoids should be limited in patients with known congestive heart failure (CHF), as they may increase the risk of CHF exacerbations (Ogdie et al. 2015). Likewise, glucocorticoids should be avoided in patients with diabetes given their hyperglycemic effects. Methotrexate should be used with caution in patients with obesity and/or diabetes, as there may be an increased risk of elevated liver function test abnormalities and liver fibrosis (Ogdie et al. 2015). For patients with known CHF New York Heart Association (NYHA) class III or IV, TNF antagonists should be avoided due to limited data (Ogdie et al. 2015). Observational data do not suggest a risk of new-onset CHF in patients being treated with TNF antagonist (Ogdie et al. 2015). Although initial studies with interleukin (IL) 12/23 antagonist therapy, briakinumab and ustekinumab, raised interest in a possible increased risk for cardiovascular events, extended studies with ustekinumab have not demonstrated substantial cardiovascular risk in PsO patients and rare events in PsA clinical trials (McKeage 2014).
Risankizumab for the treatment of moderate to severe psoriasis
Published in Expert Opinion on Biological Therapy, 2019
Andrea Chiricozzi, Luca Antonioli, Salvatore Panduri, Matteo Fornai, Marco Romanelli, Corrado Blandizzi
No safety concerns related to the use of risankizumab have emerged from the phase III trials, even though the occurrence of rare cases of MACEs will make long-term evaluations of this important, class of AEs. Since the clinical development of briakinumab, a fully human monoclonal antibody directed against the IL-12/IL-23p40 subunit, was discontinued due to higher rates of MACEs as compared to placebo, the IL-12/IL-23 inhibition was hypothesized to induce instability of atherosclerotic plaques. However, no warning signals about MACEs have been associated with ustekinumab over the 9 years of clinical usage, which has shown, across national and international registries, the safest profile among the antipsoriatic systemic drugs to date. When compared to ustekinumab, risankizumab is able to inhibit selectively the pathogenic signal mediated by IL-23, thus preserving the IL-12/IFN-γ signaling that is pivotal to both anti-viral and anti-cancer immune-surveillance. However, the robust safety profile, generated by long-term registry data related to the clinical use of ustekinumab, does not support any advantage of blocking the p19 subunit, in terms of safety implications, as compared to the p40 inhibition [42–45]. By contrast, risankizumab might be advantageous over the IL-17/IL-17-receptor blockers in terms of risk of candida infections. Indeed, no harmful signals, in the short- and mid-term period, have been associated with risankizumab, even though mice models do suggest a central role of IL-23 in candida infections [19,46].
Targeting IL-23 in Crohn’s disease
Published in Expert Review of Clinical Immunology, 2018
Silvia Sedda, Gerolamo Bevivino, Giovanni Monteleone
The first study investigating the effect of a neutralizing IL-12/IL-23p40 antibody in CD was a multicenter, randomized, placebo-controlled, phase II clinical trial, which was conducted to assess safety and efficacy of ABT-874/J695 (briakinumab), in patients with active CD [41]. Briakinumab is a recombinant full-length IgG1 antibody targeting IL-12/IL-23p40 and, hence, preventing binding of these two cytokines with their receptors. Seventy-nine patients with moderate-to-severe CD were randomized to receive 7 weekly subcutaneous injections of 1 mg or 3 mg of briakinumab per kilogram of body weight or placebo. Cohort 1 received one injection followed 4 weeks later by one injection per week for 6 weeks, and Cohort 2 received one injection per week for seven weeks [41]. Patients in Cohort 1 were seen two weeks after the first injection and at weekly intervals coinciding with the next six injections; patients in Cohort 2 were seen weekly during the 7-week treatment phase. All patients were followed for 18 weeks after the final injection of study drug and were seen at 6, 12, and 18 weeks. In patients in cohort 1, the rates of clinical response and remission did not differ between the two doses of the drug and placebo at weeks 4, 9, and 18. In contrast, in cohort 2, the clinical response rate was higher in patients receiving 3 mg briakinumab than in those treated with 1 mg briakinumab or placebo at week 7, but were no longer significant at the end of follow up (week 18). The low dose of monoclonal antibody used in the trial may have contributed to the limited benefit of the treatment. Patients receiving briakinumab exhibited reduced production of inflammatory cytokines (i.e. IL-12, IFN-γ, TNF-α) in the gut. The adverse events were documented in more than 10% of patients but were not significantly different among groups, with the exception of skin reaction at injection site, which in cohort 2 was more frequent among patients receiving briakinumab than in those treated with placebo [41].
Anti-CD6 mAbs for the treatment of psoriasis
Published in Expert Opinion on Biological Therapy, 2020
Sunil Dogra, Shabeer D, Murlidhar Rajagopalan
Itolizumab has better side effect profile but lower efficacy than other biologicals like infliximab, secukinumab in psoriasis [63]. In a recently published network meta-analysis comparative efficacy and safety of thirteen biologic therapies for patients with moderate or severe psoriasis, except placebo, briakinumab (0.913) had lowest headache risk and itolizumab (0.851) performed best in infection while ustekinumab (0.874) performed best under the discontinuation endpoint. However, published data is missing on PASI 100 as primary efficacy end point with alefacept, efalizumab, and itolizumab in psoriasis [50]. Clinical experience and various published studies suggest that Itolizumab is particularly useful in stable plaque psoriasis as monotherapy with good safety profile. Its potential advantage over anti TNF biologics is less predisposition to risk of tuberculosis, serious systemic infections or cardiovascular and neurological adverse effects. Comparative analysis indicates longer remission period with Itolizumab as compared to most of other biologics used in psoriasis. The significant limitation with itolizumab use is its intravenous route of administration, infusion reactions and relatively slow onset of action as compared to adalimumab, infliximab and anti IL17/23 biologicals in psoriasis. However, infusion reactions are generally mild noted in early infusions which can be prevented or minimized by premeditations and slowing rate of infusions. Also there is limited published data on its role in unstable, pustular, and erthrodermic psoriasis and moderate efficacy in psoriatic arthritis. It is plausible to use cyclosporine (3–5 mg/kg/day) in initial 2–4 weeks followed by itolizumab to induce fast disease clearance or in combination with methotrexate 10–15 mg/week or apremilast 30–60 mg/day to achieve early and maintain optimum PASI response particularly in patients with severe and unstable disease [64]. The availability of subcutaneous formulations of itolizumab or new anti CD6 molecules in the future may make its position stronger among the biologicals armamentarium of psoriasis therapeutics.
Related Knowledge Centers
- Monoclonal Antibody
- Rheumatoid Arthritis
- Inflammatory Bowel Disease
- Multiple Sclerosis
- Drug Development
- Psoriasis
- Ustekinumab
- Interleukin
- Clinical Trial
- Crohn's Disease