The following material represents a subset of new drugs, drug approvals, drug warnings, and drugs removed from the market from the past six months. This is not a complete list; it includes those topics considered by the authors and editors to be of particular interest or importance. For a complete list of new drug approvals, see /lco/action/index/newapprovals/patch_f (an additional subscription may be required).
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GENERAL DRUG THERAPY
CDC updates opioid prescribing guidelines (November 2022)
The United States Centers for Disease Control and Prevention (CDC) has published a new guideline for prescribing opioids for acute, subacute, and chronic pain, updating their 2016 guideline (table 1). The guideline is intended for clinicians who prescribe opioids to outpatients ≥18 years of age and does not apply to pain related to sickle cell disease, cancer, palliative care, or end of life care [1]. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Opioid therapy in the context of the opioid epidemic'.)
Morning versus bedtime dosing of once-daily antihypertensive medications (October 2022)
The best time of day to take once-daily antihypertensive medications was previously controversial, and some studies found that bedtime dosing lowered nocturnal blood pressure and improved cardiovascular outcomes. In the largest and most rigorous trial (ie, the Treatment In the Morning or Evening [TIME] study), more than 21,000 adults with hypertension were randomly assigned to take their antihypertensive medications in the morning or the evening [2]. At approximately five years, rates of cardiovascular outcomes were similar between the groups, as were adverse events. This study indicates that patients can take their once-daily antihypertensive medications at a time that they find most suitable. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Bedtime versus morning dosing'.)
Antibiotic prophylaxis against endocarditis before invasive dental procedures (September 2022)
The efficacy of antibiotic prophylaxis for prevention of infective endocarditis (IE) has not been established. A case-crossover analysis and cohort study performed in nearly 8 million individuals identified an association between invasive dental procedures (particularly extractions and oral surgery) and subsequent IE in individuals at high IE risk [3]. Antibiotic prophylaxis was associated with reduced risk of IE after these procedures. These findings support administration of antibiotic prophylaxis to individuals with high IE risk undergoing invasive dental procedures. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures", section on 'Impact of procedures on risk of endocarditis'.)
Anticoagulation for rheumatic mitral stenosis with atrial fibrillation (September 2022)
Limited data have been available to guide anticoagulant choice in patients with rheumatic mitral stenosis and atrial fibrillation. A randomized trial enrolling over 4500 adults with rheumatic heart disease and atrial fibrillation found that the mortality and stroke rates were higher with rivaroxaban than with a vitamin K antagonist (VKA), and major bleeding rates were similar [4]. Based on these findings, for patients with rheumatic mitral stenosis and atrial fibrillation, we now recommend a VKA rather than a direct oral anticoagulant such as rivaroxaban. (See "Rheumatic mitral stenosis: Overview of management", section on 'Choice of anticoagulant'.)
Efficacy of moderate-dose statin plus ezetimibe for secondary prevention of cardiovascular disease (September 2022)
The long-term efficacy of combination therapy with ezetimibe plus a moderate-dose statin for the secondary prevention of cardiovascular disease (CVD) has not been well studied. In the RACING trial, which randomly assigned nearly 3800 patients with CVD to combination therapy with moderate-dose rosuvastatin plus ezetimibe or high-dose rosuvastatin monotherapy, rates of a composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at three years were similar between the treatment groups (9.1 versus 9.9 percent, respectively) [5]. Patients receiving combination therapy were more likely to have low-density lipoprotein cholesterol <70 mg/dL, and discontinuation or dose reduction of the study drug was less frequent in the combination versus monotherapy group. In patients with CVD, ezetimibe plus a moderate-dose statin may be an alternative to high-dose statin therapy, particularly in those with an intolerance to high-dose statins. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease", section on 'Combination therapies'.)
Tirzepatide for obesity treatment (June 2022)
Treatment of obesity with glucagon-like peptide-1 (GLP-1) agonists is very effective, but treatment with a dual-acting GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist may be more effective. In a randomized controlled trial including over 2500 adults with obesity (but without diabetes), the dual GIP/GLP-1 receptor agonist tirzepatide once weekly was compared with placebo [6]. At 72 weeks, reduction in body weight at all tirzepatide doses (5, 10, and 15 mg administered subcutaneously once weekly) was greater compared with placebo (-16.1, -22.2, and -23.6 kg, respectively, versus -2.4 kg). While tirzepatide is effective for obesity management in patients with and without diabetes, it does not have regulatory approval for the treatment of obesity alone. (See "Obesity in adults: Drug therapy", section on 'Dual-acting GLP-1 and GIP receptor agonists'.)
DRUG OR INDICATION WITHDRAWALS
Belantamab mafodotin withdrawn from market (December 2022)
Belantamab mafodotin is being withdrawn from the market beginning November 2022, although it remains accessible through the manufacturer for patients who started treatment prior to its withdrawal [7]. The antibody drug conjugate targeting B-cell maturation antigen (BCMA) had received accelerated approval in the United States for patients with relapsed or refractory multiple myeloma (MM) based on response data from two uncontrolled open-label trials (DREAMM-1 and DREAMM-2). However, initial results of a randomized phase 3 trial (DREAMM-3) of belantamab mafodotin versus pomalidomide and dexamethasone in relapsed or refractory MM have not confirmed clinical benefit, leading to market withdrawal. (See "Multiple myeloma: Treatment of third or later relapse", section on 'Belantamab mafodotin'.)
ADVERSE REACTIONS AND WARNINGS
Risk of drug overdose in young people prescribed benzodiazepines for sleep disorders (December 2022)
Prescription database studies indicate that benzodiazepines are commonly prescribed for insomnia, despite risks and the availability of safer options. In a recent cohort study in the United States that included over 90,000 children and young adults (age 10 to 29 years) with a sleep disorder who were prescribed a new insomnia medication, benzodiazepines were associated with increased risk of drug overdose in the next six months compared with alternative insomnia medications (trazodone, hydroxyzine, zolpidem, zaleplon, eszopiclone) [8]. Risk was highest among individuals who had also received an opioid prescription in the preceding three months. We do not prescribe benzodiazepines for insomnia in patients taking opioids or in those with a substance use disorder. (See "Pharmacotherapy for insomnia in adults", section on 'Shared warnings and precautions'.)
Progestogens and risk of venous thromboembolism (September 2022)
Historically, estrogens but not progestogens were avoided in patients at increased risk of venous thromboembolism (VTE) who desired contraception or experienced abnormal uterine bleeding. In a case-control study that matched >21,000 reproductive-age patients with acute VTE with patients without prior VTE, current use of depot medroxyprogesterone acetate (DMPA), norethindrone acetate, or MPA was associated with an increased risk of VTE compared with non-use; the levonorgestrel-releasing intrauterine device and oral norethindrone were not associated with increased risk [9]. Study limitations included potential bias from patient selection and treatment indication. When counseling any patient about use of DMPA or high dose oral progestogens, we discuss the possibly increased risk of VTE and consider the patient's other potential risk factors for VTE when making treatment decisions. (See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Cardiovascular and thromboembolic risk'.)
Dexmedetomidine and delirium in critically ill patients (August 2022)
Data have been conflicting regarding clinical benefit associated with dexmedetomidine as a sedative in critically ill patients. A recent meta-analysis of 77 randomized trials (almost 12,000 patients) reported that compared with other sedatives, dexmedetomidine reduced the risk of delirium (relative risk 0.67, 95% CI 0.55-0.81; moderate certainty) but increased the risk of bradycardia and hypotension [10]. We agree with a recent guideline committee that dexmedetomidine can be successfully used as a sedative when the goal of reducing delirium is outweighed by the undesirable effects of hypotension and bradycardia [11]. (See "Sedative-analgesic medications in critically ill adults: Properties, dose regimens, and adverse effects", section on 'Efficacy'.)
RECENT APPROVALS - ANTIMICROBIALS
Ibrexafungerp for recurrent vulvovaginal candidiasis (December 2022)
Treatment of recurrent vulvovaginal candidiasis (RVVC) has mainly consisted of long-term use of azole drugs such as fluconazole. In a phase 3 trial evaluating extended treatment with either ibrexafungerp, a novel triterpenoid antifungal, or placebo after initial fluconazole treatment in patients with RVVC, more patients receiving extended ibrexafungerp remained without evidence of RVVC four weeks from final dose (65 versus 53 percent). Based on this trial, the US Food and Drug Administration recently approved RVVC as a new indication for use of ibrexafungerp [12]. Although the duration of treatment benefit and efficacy against non-Candida species are not yet known, ibrexafungerp offers patients with RVVC another treatment option. (See "Candida vulvovaginitis: Treatment", section on 'Triterpenoid extended treatment'.)
Treatment of recurrent vulvovaginal candidiasis (July 2022)
Patients with recurrent vulvovaginal candidiasis (RVVC, defined as ≥3 culture-confirmed episodes in ≤12 months) who do not respond to oral fluconazole therapy have had few other treatment options. In an industry-sponsored trial comparing treatment and maintenance with either oteseconazole (a novel azole) or fluconazole/placebo in 185 females with active RVVC, fewer patients receiving oteseconazole experienced ≥1 culture-confirmed candidiasis episodes during the 48-week maintenance phase compared with fluconazole/placebo (5 versus 42 percent, respectively) [13]. Where available, oteseconazole is a therapeutic option for patients with culture-confirmed RVVC who do not respond to fluconazole therapy and who are not pregnant, attempting pregnancy, or lactating. (See "Candida vulvovaginitis: Treatment".)
RECENT APPROVALS - DERMATOLOGIC AND ALLERGY THERAPIES
Topical ruxolitinib for limited nonsegmental vitiligo (October 2022)
Vitiligo is a difficult-to-treat autoimmune skin disease characterized by depigmented patches. In two recent identical randomized trials that included 674 patients with nonsegmental vitiligo involving ≤10 percent of total body surface area, more patients assigned to twice daily ruxolitinib 1.5% cream (a topical Janus kinase inhibitor) achieved a 75 percent reduction in the facial Vitiligo Area Scoring Index at 24 weeks, compared with vehicle (30 versus 7 percent [trial 1] and 31 percent versus 11 percent [trial 2]) [14]. Ruxolitinib-related adverse events included acne and pruritus at the site of application and nasopharyngitis. These studies were the basis for the US Food and Drug Administration approval for this indication. However, due to safety concerns related to systemic absorption of ruxolitinib, we continue to suggest topical corticosteroids and topical calcineurin inhibitors as initial treatments for limited vitiligo. (See "Vitiligo: Management and prognosis", section on 'Localized disease'.)
Oral deucravacitinib for moderate to severe plaque psoriasis (October 2022)
Tyrosine kinase inhibition represents a novel approach to psoriasis treatment. Two phase 3 trials support efficacy of oral deucravacitinib, a selective tyrosine kinase 2 inhibitor, for moderate to severe plaque psoriasis [15,16]. In the POETYK PSO-1 and POETYK PSO-2 trials, adults with moderate to severe plaque psoriasis were randomly assigned to deucravacitinib, placebo, or apremilast. At week 16, patients treated with deucravacitinib were more likely to achieve at least 75 percent improvement in the Psoriasis Area and Severity Index score than patients in the placebo or apremilast groups (58, 13, and 35 percent in POETYK PSO-1 and 53, 9, and 40 percent in POETYK PSO-2, respectively). Serious adverse effects were infrequent in both trials. These findings support deucravacitinib as an effective oral treatment for psoriasis and contributed to FDA approval of deucravacitinib for moderate to severe psoriasis in adults who are candidates for systemic therapy or phototherapy. Additional study will be useful for determining long-term efficacy and safety. (See "Treatment of psoriasis in adults", section on 'Deucravacitinib'.)
Oral baricitinib for alopecia areata (August 2022)
Effective therapies for severe alopecia areata are limited. Two phase 3 trials support the efficacy of baricitinib, an oral Janus kinase (JAK) 1 and JAK2 inhibitor [17]. In BRAVE-AA1 (n = 654) and BRAVE-AA2 (n = 546), adults with severe alopecia areata were randomly assigned to baricitinib 4 mg per day, baricitinib 2 mg per day, or placebo. After 36 weeks, patients treated with either dose of baricitinib were more likely to achieve the specified level of improvement in the alopecia severity score than patients in the placebo group. Acne, elevated levels of creatinine kinase, and elevated levels of low density lipoprotein cholesterol and high density lipoprotein cholesterol occurred more frequently in the baricitinib groups than the placebo group. These findings support baricitinib as a preferred therapy for severe alopecia areata in adults and contributed to US Food and Drug Administration approval for this indication. However, uncertainty remains about long-term efficacy and safety. (See "Alopecia areata: Management", section on 'Other Janus kinase inhibitors'.)
RECENT APPROVALS - HEMATOLOGIC AND ANTICOAGULANT
Bispecific T cell engager (BiTE) teclistamab in multiple myeloma (November 2022)
Therapies that target the B cell maturation antigen (BCMA) are a preferred treatment option for patients with penta-refractory multiple myeloma (MM), defined as disease refractory to an anti-CD38 monoclonal antibody, lenalidomide, pomalidomide, bortezomib, and carfilzomib (algorithm 1). In a single-arm, phase 2, multicenter trial (MajesTEC-1) of the first-in-class anti-BCMA bispecific T-cell engager (BiTE) teclistamab in multiply relapsed MM, objective responses were seen in 63 percent, with an estimated progression-free survival of 11 months [18]. At least one grade 3 or 4 toxicity was reported in 95 percent of patients, with hematologic toxicity being most common. Cytokine release syndrome occurred in 73 percent and was usually grade 1 or 2. Based on this data, teclistamab has received accelerated approval by the US Food and Drug Administration for treatment of adults with relapsed, refractory MM after four or more lines of systemic therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody [19]. The use of teclistamab and other BCMA-directed therapies is individualized, weighing disease tempo, availability of other treatments, and expected toxicity. (See "Multiple myeloma: Treatment of third or later relapse".)
RECENT APPROVALS - NEUROLOGIC AND PSYCHIATRIC
Sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis (October 2022)
Sodium phenylbutyrate-taurursodiol (PB-TURSO) is a combination of two orally available drugs that each reduce neuronal cell death in preclinical models of amyotrophic lateral sclerosis (ALS). In a randomized trial of 137 patients with ALS (75 percent also taking riluzole and/or edaravone) who were within 18 months of symptom onset, patients assigned to PB-TURSO showed a slower median rate of monthly functional decline than those assigned to placebo by 24-week follow-up [20]. There were nonsignificant trends toward slower decline in both vital capacity and muscle strength with treatment. In a subsequent analysis of patients who continued open-label treatment (up to 35 months), those originally randomized to PB-TURSO had a longer median time to tracheostomy (26 versus 19 months) and a longer median time to first hospitalization [21]. Based on these results, the combination product received regulatory approval in the United States and Canada [22,23]. We now suggest use of PB-TURSO for all patients with ALS, along with riluzole (prioritized as initial therapy) and edaravone. (See "Disease-modifying treatment of amyotrophic lateral sclerosis", section on 'Efficacy'.)
RECENT APPROVALS - ONCOLOGIC
Mirvetuximab soravtansine in platinum-resistant epithelial ovarian cancer (November 2022)
Mirvetuximab soravtansine is a folate receptor alpha-directed antibody and microtubule inhibitor conjugate that has regulatory approval in the United States for folate receptor-alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) that has previously been treated with one to three prior systemic treatment regimens [24]. In an earlier randomized trial in patients with platinum-resistant EOC, the agent resulted in a nonsignificant trend towards better progression-free survival compared with investigator's choice chemotherapy in those with folate receptor-alpha high tumors (hazard ratio 0.69), with better tolerability. We consider mirvetuximab soravtansine to be an appropriate later-line option in platinum-resistant EOC. (See "Medical treatment for relapsed epithelial ovarian, fallopian tube, or peritoneal cancer: Platinum-resistant disease", section on 'Other agents'.)
Immune checkpoint inhibitor combinations plus chemotherapy in advanced NSCLC (November 2022)
The addition of immune checkpoint inhibitors to chemotherapy improves survival in advanced non-small cell lung cancer (NSCLC), with new combinations being investigated. In preliminary results of Study 16113, among 466 patients randomly assigned to chemotherapy with or without cemiplimab, the cemiplimab group experienced an improvement in median overall survival (22 versus 13 months), with low rates of serious adverse events [25]. Similarly, in the POSEIDON trial, the addition of tremelimumab plus durvalumab to chemotherapy improved median survival (15 versus 11 months), with acceptable rates of grade ≥3 toxicity [26]. These results have led to US Food and Drug Administration approvals of combinations of cemiplimab as well as tremelimumab/durvalumab with chemotherapy in advanced NSCLC lacking certain driver mutations. (See "Management of advanced non-small cell lung cancer lacking a driver mutation: Immunotherapy", section on 'Cemiplimab plus chemotherapy'.)
Tissue-agnostic approval of selpercatinib for RET fusion-positive solid tumors (November 2022)
Selpercatinib has received a tissue-agnostic, accelerated approval from the US Food and Drug Administration for treatment of adult patients with locally advanced or metastatic solid tumors and a rearranged during transfection (RET) gene fusion with disease progression on or following prior systemic treatment or those who have no satisfactory alternative treatment options. Approval was based on the phase 1/2 LIBRETTO-001 basket trial of 41 patients with a variety of solid tumors containing an RET fusion gene, in which the objective response rate was 44 percent and median duration of response was 24.5 months [27]. The most common grade 3 or worse treatment-emergent adverse events were hypertension and elevated serum transaminases. (See "Systemic therapy for nonoperable metastatic colorectal cancer: Approach to later lines of systemic therapy", section on 'RET fusion-positive tumors' and "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease", section on 'RET fusion-positive tumors'.)
Futibatinib for advanced intrahepatic cholangiocarcinoma with an FGFR2 gene fusion or rearrangement (October 2022)
Futibatinib, a highly selective inhibitor of fibroblast growth factor receptor (FGFR) 1 to 4, has been approved by the US Food and Drug Administration for treatment of locally advanced/metastatic intrahepatic cholangiocarcinoma with an FGFR2 gene fusion or rearrangement [28]. Approval was based on the phase II FOENIX-CCA2 study, which showed an objective response rate of 42 percent, a mean duration of response of 9.5 months, and no new safety signals [29]. The most common treatment-related adverse effects were hyperphosphatemia, alopecia, dry mouth, diarrhea, dry skin, and fatigue. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'FGFR inhibitors for FGFR fusion-positive tumors'.)
Durvalumab for locally advanced or metastatic biliary tract cancer (September 2022)
The US Food and Drug Administration has approved durvalumab, an antiprogrammed cell death ligand 1 monoclonal antibody, in combination with cisplatin and gemcitabine for adults with previously untreated locally advanced or unresectable biliary tract cancer. Approval was based on the TOPAZ-1 trial, which directly compared cisplatin and gemcitabine with or without durvalumab for up to 24 weeks; those in the durvalumab group received ongoing monthly durvalumab until disease progression or toxicity [30]. Durvalumab improved objective response rates and modestly improved median overall survival (12.8 versus 11.5 months), but more than twice as many individuals were still alive at 24 months (25 versus 10 percent). There was no added toxicity compared with chemotherapy alone. In our view, durvalumab plus cisplatin and gemcitabine is an option, but not necessarily preferred, for first-line treatment of advanced cholangiocarcinoma. We individualize decision-making based on patient preference, insurance coverage, and drug availability. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'Gemcitabine plus cisplatin and durvalumab'.)
Eflapegrastim for chemotherapy-induced neutropenia (September 2022)
The US Food and Drug Administration has approved eflapegrastim, a novel long-acting formulation of granulocyte colony stimulating factor (G-CSF), to decrease the incidence of infection in adult patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia [31]. Approval was based on two separate trials of patients with early-stage breast cancer treated with docetaxel plus cyclophosphamide and randomized to eflapegrastim or pegfilgrastim. Efficacy was comparable, but despite the lower G-CSF dose with eflapegrastim, the incidence of adverse events (ie, bone pain, injection site reactions) was not lower in either trial. Given the available data, these two medications appear clinically similar, and agent selection may depend largely on institutional formulary and insurance constraints. (See "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation", section on 'Eflapegrastim'.)
Sodium thiosulfate to reduce cisplatin ototoxicity in children with nonmetastatic solid tumors (September 2022)
Sodium thiosulfate (STS) has been approved by the US Food and Drug Administration to decrease the risk of cisplatin-related ototoxicity in pediatric patients aged 1 month or older with a localized, nonmetastatic solid malignancy [32]. Approval was based on two randomized trials, the Children's Oncology Group ACCL0431 trial and the SIOPEL-6 trial, which both demonstrated a lower incidence of ototoxicity among children treated with STS in the setting of hepatoblastoma or a solid tumor including germ cell cancer, medulloblastoma, neuroblastoma, or osteosarcoma. Given ongoing concerns about possible inferior oncologic outcomes, the approval was not extended to individuals with a metastatic solid tumor. The approved dose is based on actual body weight, as outlined in the US prescribing information [33]. (See "Overview of neurologic complications of platinum-based chemotherapy", section on 'Strategies'.)
Crizotinib for ALK-positive inflammatory myofibroblastic tumor (August 2022)
Inflammatory myofibroblastic tumor (IMT) is a rare chemotherapy-resistant sarcoma, and there is interest in novel targeted therapies for patients with advanced disease. In two separate open-label phase I/II trials in patients with unresectable, recurrent, or refractory IMT harboring an ALK gene rearrangement, crizotinib demonstrated objective response rates of 86 percent among children (12 of 14 patients) and 71 percent among adults (5 of 7 patients) with no new toxicity signals [34]. Based on these data, the US Food and Drug Administration approved crizotinib for adult and pediatric patients with unresectable, recurrent, or refractory IMT harboring an ALK gene rearrangement, and we also suggest initial treatment with crizotinib in this population. (See "Uncommon sarcoma subtypes", section on 'ALK-mutated tumors'.)
Tissue-agnostic approval for dabrafenib plus trametinib in BRAF V600E-mutated tumors (June 2022)
Combined therapy with the BRAF and MEK inhibitors dabrafenib and trametinib has been granted a tissue-agnostic accelerated approval by the US Food and Drug Administration for the treatment of patients ≥6 years of age with unresectable or metastatic solid tumors harboring mutations in BRAF V600E following progression on previous treatment and with no satisfactory alternative treatment options [35]. Approval was based on data from the open-label phase II ROAR and NCI-MATCH trials that demonstrated objective response rates in a variety of refractory solid tumors with data from the open-label phase II ROAR and NCI-MATCH trials that demonstrated objective response rates in a variety of refractory solid tumors with V600E mutations, which were highest (up to 50 percent) in gliomas and biliary tract, gynecologic, and gastrointestinal (but not colorectal) tumors [36,37]. The most common adverse events in the NCI MATCH trial were fatigue, nausea, and fever and chills. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'BRAF V600E-mutated cancers'.)
RECENT APPROVALS - OTHER
Trial of intravenous immune globulin for dermatomyositis (November 2022)
Intravenous immune globulin (IVIG) has been used in the treatment of dermatomyositis (DM) based on limited observational data and small randomized trials. In a new randomized trial of 95 patients with DM, the percentage of patients who achieved a response of at least minimal improvement based on a composite score of disease activity was higher among those who received IVIG compared with placebo (79 versus 44 percent) at 16 weeks [38]. IVIG was associated with more adverse events, including thromboembolic events. Based on these results, the US Food and Drug Administration approved IVIG for the treatment of adults with dermatomyositis. More data are needed to help determine the potential role of IVIG as first-line therapy for patients with DM. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults", section on 'Intravenous immune globulin'.)
Risankizumab for moderate to severe Crohn disease (July 2022)
Therapeutic options for moderate to severe Crohn disease (CD) are expanding. In two induction trials comparing 600 and 1200 mg risankizumab (an anti-interleukin 23 antibody) with placebo in adults with moderate to severe CD, risankizumab resulted in higher rates of clinical remission at 12 weeks (40 to 45 percent in the treatment groups versus 20 to 25 percent in the placebo groups) [39]. In a maintenance trial comparing risankizumab 180 or 360 mg with placebo, risankizumab resulted in higher rates of sustained remission after 52 weeks (52 and 55 percent in the treatment groups versus 41 percent in the placebo group) [40]. No safety signals were detected. Based on these data, the US Food and Drug Administration approved risankizumab for adults with moderate to severe CD. We anticipate using risankizumab as an alternative to other first-line biologic therapies. (See "Overview of medical management of high-risk, adult patients with moderate to severe Crohn disease", section on 'Other biologic agents'.)
COVID-19 MANAGEMENT
Nirmatrelvir-ritonavir in vaccinated individuals with COVID-19 (October 2022)
A large randomized trial previously demonstrated that nirmatrelvir-ritonavir (Paxlovid) substantively reduced hospitalization and death in unvaccinated individuals with COVID-19 and risk factors for severe disease; accumulating observational data suggest that high-risk vaccinated individuals also benefit. In a study of 1130 vaccinated adults who received nirmatrelvir-ritonavir within five days of COVID-19 diagnosis and 1130 controls matched for age, gender, race, and comorbidities, nirmatrelvir-ritonavir was associated with a lower rate of emergency department visits, hospitalization, and death (odds ratio 0.5) [41]. All 10 deaths were among those who had not been treated. In another study, nirmatrelvir-ritonavir was associated with a reduction in hospitalization from 59 to 15 cases per 100,000 person-days among mostly vaccinated patients ≥65 years old [42]. Despite the limitations of observational data, these data highlight the potential clinical impact of nirmatrelvir-ritonavir among vaccinated individuals with Omicron subvariant infection and support our recommendations to treat patients at risk for severe disease, including otherwise healthy individuals ≥65 years old, regardless of vaccination status (algorithm 2). (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Efficacy and rationale'.)
COVID-19 VACCINATION
Booster doses with the bivalent COVID-19 mRNA vaccines (September 2022, Modified December 2022)
Booster doses of COVID-19 vaccines are a strategy to improve effectiveness in the setting of waning immunity and immune evasion from circulating SARS-CoV-2 variants. The US Food and Drug Administration authorized two bivalent mRNA booster vaccines that target the spike proteins of both the original SARS-CoV-2 strain and the Omicron B.4/B.5 variants (figure 1 and figure 2) [43,44]. The Centers for Disease Control and Prevention (CDC) now recommends that all individuals ≥5 years old who have completed a primary COVID-19 vaccine series (including those who already received booster doses with monovalent vaccines) receive a single booster dose with one of the bivalent vaccines at least two months after the last vaccine dose; bivalent booster recommendations for children younger than five years old depend on the primary series vaccine received (table 2) [45]. Our approach is consistent with CDC recommendations. Although clinical data evaluating bivalent vaccines are limited, their use is supported by indirect evidence from trials and observational studies in which monovalent booster doses improved vaccine efficacy against infection and severe disease and by studies that indicate at least comparable immunogenicity with bivalent versus monovalent formulations. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations'.)
Novavax COVID-19 vaccine in the United States (July 2022)
In July 2022, the US Food and Drug Administration issued an emergency use authorization for NVX-CoV2373 (Novavax COVID-19 vaccine) for individuals aged 12 years or older, and the Centers for Disease Control and Prevention subsequently recommended it as an option for COVID-19 vaccination [46]. It is an adjuvanted recombinant protein vaccine, similar to other long-available non-COVID-19 vaccines. In trials conducted prior to the emergence of the Delta and Omicron variants, NVX-CoV2373 efficacy in preventing symptomatic COVID-19 was 90 percent in adults; rare cases of myocarditis were reported among vaccine recipients [47,48]. NVX-CoV2373 may be an attractive option for individuals who prefer a COVID-19 vaccine created with a more established vaccine platform. (See "COVID-19: Vaccines", section on 'Available vaccines'.)
No evidence that PEG is the cause of allergic reactions to mRNA COVID-19 vaccines (July 2022)
When initial reports of allergic reactions to SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccines appeared, the excipient polyethylene glycol (PEG) 2000 was implicated as the possible causative agent because higher molecular weight PEGs and related polysorbates have rarely caused anaphylaxis. However, several case series have documented uneventful mRNA vaccinations in a total of over 300 patients who had known or probable PEG allergy and past reactions to PEG-containing medications [49,50]. These findings suggest that PEG 2000 is not the likely cause of apparent anaphylaxis after vaccination with mRNA vaccines. Patients with past allergic reactions to PEG or polysorbate in other medications can safely receive mRNA COVID-19 vaccines without prior PEG skin testing or other special precautions. (See "COVID-19: Allergic reactions to SARS-CoV-2 vaccines", section on 'Uncertain role of polyethylene glycol'.)
Vaccination status and prevalence of "long COVID" symptoms (July 2022)
In a new prospective observational cohort study of 2560 patients with mild COVID-19, COVID-19 vaccination was associated with a decreased prevalence of postacute sequelae of SARS-CoV-2 infection (PASC) in a dose-dependent fashion (three doses 16 percent, two doses 17.4 percent, and one dose 30 percent) compared with unvaccinated individuals (42.8 percent) [51]. This finding appeared to be independent from the COVID-19 variant. This study provides additional evidence that COVID-19 vaccination, in addition to reducing the risk of COVID-19 infection, may also decrease PASC in vaccinated patients with mild infection. (See "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")", section on 'Prevention of post-COVID conditions'.)
COVID-19 vaccination in patients with inflammatory bowel disease (July 2022)
Data on the immunogenicity of COVID-19 vaccines in patients with inflammatory bowel disease (IBD) are accumulating. In a meta-analysis of 31 studies including nearly 9500 patients with IBD who completed a COVID-19 vaccination series, the pooled seroconversion rate was 96 percent [52]. Seroconversion rates were not significantly different by drug therapy (ie, biologics, small molecules, immunomodulators, and/or glucocorticoids). In most studies that reported durability of serologic response, antibody titers began declining four weeks after vaccination. These data provide some reassurance for patients on immunosuppressive medications and lend support for additional vaccine doses in patients with IBD. (See "COVID-19: Issues related to gastrointestinal disease in adults", section on 'COVID-19 vaccination'.)
VACCINES - OTHER
Expanded ACIP recommendations for oral cholera vaccine (October 2022)
CVD 103-HgR (Vaxchora) is a single-dose, live attenuated oral cholera vaccine derived from Vibrio cholerae serotype O1; it was licensed by the US Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices (ACIP) in 2016 for adults age 18 to 64 years traveling to areas of active cholera transmission. In 2022, the ACIP expanded the age group to include individuals age 2 to 17 years who meet these criteria [53]. Thus far, assessment of CVD 103-HgR vaccine benefit in children has been based on safety and immunogenicity data rather than direct assessment of vaccine efficacy. We are in agreement with this guidance. (See "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'For travelers to high-risk areas'.)
Updated recommendations for pneumococcal vaccination in children and adolescents (September 2022)
Updated guidance from the Advisory Committee on Immunization Practices (ACIP) permits interchangeable use of the recently licensed 15-valent pneumococcal conjugate vaccine (PCV15) and 13-valent PCV (PCV13) for routine infant immunization and immunization of high-risk children and adolescents (table 3) [54]. PCV15 contains the 13 serotypes included in PCV13 plus serotypes 22F and 33F (table 4), which accounted for 15 to 23 percent of invasive pneumococcal disease cases in children <18 years in the United States during 2018 to 2019. In prelicensure randomized trials, PCV15 demonstrated immunogenicity and safety similar to those of PCV13. We agree with the ACIP recommendations for PCV15. Clinical trials of the 20-valent PCV in children are ongoing. (See "Pneumococcal vaccination in children", section on 'Conjugate vaccines'.)
New ACIP recommendations for seasonal influenza vaccination (September 2022)
In August 2022, the Advisory Committee on Immunization Practices (ACIP) issued new recommendations for seasonal influenza vaccination in the United States [55]. The ACIP now recommends that adults aged ≥65 years preferentially receive any one of the following higher dose or adjuvanted influenza vaccines: quadrivalent high-dose inactivated influenza vaccine (HD-IIV4), quadrivalent recombinant influenza vaccine (RIV4), or quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) (table 5). In addition, the approved age indication for the cell culture–based inactivated influenza vaccine has been changed from ≥2 years to ≥6 months. We are in agreement with this guidance. (See "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Seasonal influenza in children: Prevention with vaccines", section on 'Influenza vaccines'.)
Vaccine-derived poliovirus infection in Rockland County, New York (August 2022)
In June 2022, poliovirus was confirmed in an unvaccinated, immunocompetent adult resident of Rockland County, New York hospitalized with acute flaccid lower limb weakness [56]. Vaccine-derived poliovirus type 2 was detected in the patient's stool and was also identified from wastewater samples in two neighboring New York counties, reflecting community transmission. The patient had not traveled internationally during the presumed exposure period; therefore, these findings suggest transmission within the United States from a person who received a type 2-containing oral polio vaccine abroad. Unvaccinated individuals remain at risk for paralytic poliomyelitis if they are exposed to either wild or vaccine-derived poliovirus; all individuals should stay up to date on recommended poliovirus vaccination. (See "Poliomyelitis and post-polio syndrome", section on 'Epidemiology'.)
Modified vaccinia Ankara vaccine for monkeypox postexposure prophylaxis (August 2022)
During the 2022 monkeypox outbreak, a modified vaccinia Ankara (MVA) vaccine is being used for postexposure prophylaxis after known or likely exposure. In the United States, given limited vaccine supplies, emergency use authorization was granted for intradermal MVA administration in persons ≥18 years; younger individuals should continue to receive the vaccine subcutaneously [57]. Intradermal administration uses a lower dose compared with the standard subcutaneous route, thus maximizing vaccine supply, and clinical trials suggest similar immunogenicity. However, data on the efficacy of postexposure prophylaxis and intradermal administration remain limited; patients who receive the vaccine should continue to monitor for symptoms after an exposure and reduce their risk of new exposures. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses", section on 'Dose-sparing regimen'.)
