Cost per cumulative clinical benefit of biologic therapies for patients with plaque psoriasis: a systematic review.

BACKGROUND: Measuring cumulative clinical treatment benefit over time captures speed and magnitude of effects. Assessing the cost of biologics relative to their cumulative clinical benefits versus a single time point represents an alternative to evaluate the value of a given biologic used to treat psoriasis. OBJECTIVE: To compare cumulative benefit and cost per cumulative benefit of biologics in treatment of moderate to severe psoriasis from a network meta-analysis (NMA). METHODS: Biologics included in the analysis were ixekizumab, adalimumab, guselkumab, ustekinumab, secukinumab, risankizumab, and certolizumab pegol. Psoriasis Area and Severity Index (PASI) responses over the initial 16-week treatment period were obtained from 31 articles. Cumulative benefits for PASI 75, PASI 90, and PASI 100 responses were measured as area under the curve (AUC) using the trapezoidal method. Bayesian-based NMA modeled percent maximum AUC through week 16 (%Max_AUCW16). The AUC estimates over 16 weeks were converted to total skin clearance threshold days achieved for PASI 75, PASI 90, and PASI 100 with each biologic. Cost per cumulative benefit was estimated by multiplying number of doses (per FDA label) by nationally representative discounted wholesale acquisition costs (WACs) for 16 weeks of treatment divided by %Max_AUCW16. The primary cost analysis used WACs, including week 16 doses. Co-primary cost analysis used discounted WACs, including week 16 doses. Sensitivity analysis was conducted using WACs and discounted WACs, excluding doses administered at week 16. RESULTS: Among biologics with available week 16 AUC data for PASI 90 and PASI 100, cumulative benefits over the initial 16-week treatment period ranged from 20.2% (certolizumab pegol) to 47.0% (ixekizumab) for PASI 90 and from 7.4% (adalimumab) to 22.2% (ixekizumab) for PASI 100. The total number of estimated PASI 90 and PASI 100 days achieved over the first 16 weeks of treatment was highest with ixekizumab (53 days and 25 days, respectively). In the primary analysis, guselkumab had the lowest cost per cumulative benefit (95% credible interval [CrI]; $99,742 [$89,941-$111,653]), followed by ixekizumab ($108,906 [$95,928-$126,093]) and adalimumab ($111,233 [$97,549-$129,022]) for PASI 90, and ixekizumab had the lowest cost per cumulative benefit ($230,884 [$191,611-$291,115]), followed by secukinumab ($238,945 [$204,029-$288,072]) and risankizumab ($279,968 [$250,683-$316,872]) for PASI 100 responses. In the co-primary analysis, ixekizumab had the lowest discounted cost per AUC (95% CrI; $60,988 [$53,719-$70,612]), followed by guselkumab ($66,827 [$60,260-$74,807]) and secukinumab ($69,622 [$61,783-$79,786]) for PASI 90, and ixekizumab had the lowest cost per cumulative benefit ($129,295 [$107,302-$163,024]), followed by secukinumab ($148,146 [$126,498-$178,605]) and guselkumab ($188,190 [$166,791-$215,969]) for PASI 100 responses. Conclusions: Among biologics studied, ixekizumab demonstrated the greatest cumulative clinical benefit, maintaining the lowest cost per cumulative benefit for PASI 100 responses and lowest discounted cost per cumulative benefit for PASI 90 and PASI 100 responses for moderate to severe psoriasis over the initial 16-week treatment period. DISCLOSURES: This study was funded by Eli Lilly and Company (Indianapolis, IN). Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Ortho, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma and as a paid speaker for AbbVie. Burge, Zhu, Malatestinic, Brnabic, Guo, and Janardhanan are employees and shareholder of Eli Lilly and Company.

Cycloserine Induced Late Onset Psychosis and Ethambutol Induced Peripheral Neuropathy Associated with MDR-TB Treatment in an Indian Patient- A Rare Case Report.

Adverse reactions and toxicity inevitably accompany all treatment courses for drug-resistant TB. Our case underscores the importance of awareness regarding neuropsychiatric adverse reactions due to MDR-TB therapy and reversible nature of it. Cycloserine induced psychosis is most life threatening complication and sometimes could be fatal. A 42-year-old male on MDR-TB therapy got admitted for his persistent psychotic complaints like hallucinations, delusions and suicidal ideations, despite being treated with quetiapine/olanzapine. Eventually patient was rehabilitated, cycloserine was stopped and psychotic events regressed slowly. Other culprit drugs like ethambutol and levofloxacin causing psychosis was ruled out because there was no relapse of psychotic events despite being continued with these drugs. He also complained of tingling, numbness, swaying, pain and weakness. On examination, he had distal motor weakness in lower limbs, tandem gait positive, altered position sense, and tenderness over toes and positive Romberg's sign with ataxia. He was diagnosed to have drug induced sensorimotor peripheral neuropathy. All these symptoms persisted after stopping cycloserine and patient continued to have neuropathy with ethambutol and ethionamide. Considering the nature of neuropathy which was mild, mixed sensorimotor and resolved completely after 2-3 weeks of stopping, it was more in favour of ethambutol. However, we could not rule out the possibility of ethionamide or (ethionamide + ethambutol) causing neuropathy or both could have accelerated the neurotoxic effects of cycloserine which remained elusive.

Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.

The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/µL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.