Patients
TB, WOCBP, neurotic excoriations, malignancy, autoimmune diseases, psychiatric, Eczema, acne, abnormal frequency or prolonged duration, investigatorActive malignancy, scabies, periodKnown, uremia, infections, psoriasis, lupus, non-tuberculous mycobacterial infection, actinic dermatitis, pneumocystosis, immune-compromised, non-metastatic squamous, diabetes, anaphylaxis, itch, listeriosis, HIV infection, HBV DNAPositive HCV Ab, CRF, delusions, infection, pruritus, sporotrichosis, heart failure, AD, dermatitis herpetiformis, neuropathy, obsessive compulsive disorder, IGA, infectious disease, atopic, insect bite, low disease activity
RHEUMATOID ARTHRITIS, OPPORTUNISTIC INFECTIONS, INFLAMMATORY BOWEL DISEASE, NEUROTIC EXCORIATION, AUTOIMMUNE DISEASES, CRF, LYMPHOMATOID PAPULOSIS, ECZEMA, ACNE, HEART, LICHEN SIMPLEX CHRONICUS, SCABIES, UREMIA, INFECTIONS, PSORIASIS, REMISSION, LUPUS, PNEUMOCYSTOSIS, CARCINOMA OF THE CERVIX, HISTOPLASMOSIS, DEMYELINATING DISEASES, DIABETES, ANAPHYLAXIS, ASPERGILLOSIS, FOLLICULITIS, LISTERIOSIS, POSITIVE, HIV INFECTION, NOTALGIA PARESTHETICA, INFECTION, SPOROTRICHOSIS, HEART FAILURE, TUBERCULOSIS (TB), ACUTE INFECTION, COCCIDIOIDOMYCOSIS, ATOPIC DERMATITIS, NEUROPATHY, DISEASE, INFECTIOUS DISEASE, SECONDARY, ATOPIC, IMMUNODEFICIENCY
Patients were enrolled in PRIME or PRIME2 if all the following inclusion criteria applied:Male or female, 18–80 years of age at the time of signing the informed consentPN diagnosed by a dermatologist for at least 3 months before the screening visitWI-NRS score of ≥7 in the 7 days before day 1 (on a scale of 0–10)Baseline pruritus NRS average score for maximum itch intensity was determined based on the average of daily NRS scores for maximum intensity (the daily score ranges from 0 to 10) during the 7 days immediately preceding randomization (a minimum of four daily scores out of the 7 days is required to calculate the baseline average score); for patients who did not have at least four daily scores reported during the 7 days immediately preceding the planned randomization date, randomization was postponed until this requirement was met but without exceeding the 28-day maximum duration of the screening period.≥20 PN lesions in total on both legs, and/or both arms and/or trunk, at screening visit and on day 1Patients needed to have bilaterally symmetrical lesions on the extremities; presence of lesions on at least two body surface areas was required.History of failing a 2-week course of medium-to-super-potent TCS or when TCS were not medically advisableFailure was defined as patients who had been unable to achieve and/or maintain remission and low disease activity (similar to IGA PN-S score of ≤2 (≤19 nodules)) despite treatment with a daily regimen of medium-to-super-potent TCS (±TCI as appropriate), applied for at least 14 days or for the maximum duration recommended by the product prescribing information, whichever was shorter.Had applied a stable dose of topical emollient (moisturizer) once or twice daily for at least five out of the seven consecutive days immediately before day 1Was willing and able to complete a daily symptom eDiary for the duration of the studyContraceptive use by women was consistent with local regulations regarding the methods of contraception for those participating in clinical studiesFemale patients were eligible to participate if they were not pregnant or breastfeeding and at least one of the following conditions applied:Is not a woman of childbearing potential (WOCBP)ORIs a WOCBP and agreed to use a contraceptive method during the study (at a minimum until 12 weeks after the last dose of study intervention)A WOCBP must have had a negative highly sensitive pregnancy test (urine or serum as required by local regulations) on day 1 before the first dose of study intervention.If a urine test could not be confirmed as negative (for example, an ambiguous result), a serum pregnancy test would be required; in such cases, the patient would be excluded from participation if the serum pregnancy result was positive.The investigator was responsible for review of medical history, menstrual history and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.Is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the study protocol; in countries where legal age of majority is above 18 years, a specific ICF was signed by the patient’s legally authorized representative.Patients were not eligible if any of the following exclusion criteria applied:Presence of skin morbidities other than PN and mild AD that may interfere with the assessment of the study outcomesConditions such as, but not limited to, the following: scabies, insect bite, lichen simplex chronicus, psoriasis, acne, folliculitis, habitual picking, lymphomatoid papulosis, chronic actinic dermatitis, dermatitis herpetiformis, sporotrichosis and bullous diseasePatients with mild active AD will have represented up to 10% of the atopic PN study population.PN secondary to medications (for example, opioids and angiotensin-converting enzyme inhibitors)PN secondary to medical conditions such as neuropathy or psychiatric disease (for example, notalgia paresthetica, brachioradial pruritus, neurotic excoriations, obsessive compulsive disorder and delusions of parasitosis)Documented moderate-to-severe AD within 6 months before the screening visit or documented diagnosis of moderate-to-severe AD from screening visit to randomization visit (for example, Investigator Global Assessment (IGA) for AD of 3 or 4, Eczema Area and Severity Index (EASI) ≥16 and SCORing Atopic Dermatitis (SCORAD) ≥25)Severe concomitant illness(es) under poor control that, in the investigator’s judgment, would adversely affect the patient’s participation in the studyExamples include, but are not limited to, patients with life expectancy shorter than 1 year; patients with uncontrolled diabetes (hemoglobin A1c ≥9% according to the laboratory results within 3 months before screening visit); patients with cardiovascular conditions (for example, class III or IV heart failure according to the New York Heart Association classification); hepatobiliary conditions (for example, Child–Pugh class B or C); neurologic conditions (for example, demyelinating diseases); active major autoimmune diseases (for example, lupus, inflammatory bowel disease and rheumatoid arthritis); and other severe endocrinological, gastrointestinal, metabolic, pulmonary or lymphatic diseases. The specific justification for patients excluded under this criterion would be noted in study documents (chart notes and electronic CRF (eCRF)).Severe renal conditions (for example, patients with uremia and/or on dialysis)Uncontrolled thyroid diseaseActive tuberculosis (TB) or non-tuberculous mycobacterial infection or a history of incompletely treated TB, unless it was well documented by a specialist that the patient had been adequately treated and can now start treatment with dupilumab in the medical judgment of the investigator and/or infectious disease specialist; TB testing was performed on a country-by-country basis, according to local guidelines if required by regulatory authorities or ethics boards.Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomizationActive chronic or acute infection (except HIV infection) requiring treatment with systemic antibiotics, antivirals, antiprotozoals or antifungals within 2 weeks before screening visit or during the screening periodKnown or suspected immunodeficiency, including history of invasive opportunistic infections (for example, TB, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis and aspergillosis) despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune-compromised status, as judged by the investigatorActive malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skinHistory of systemic hypersensitivity or anaphylaxis to any biologic therapy, including any excipientsAny other medical or psychological condition, including relevant laboratory abnormalities at screening, that, in the opinion of the investigator, suggested a new and/or insufficiently understood disease, may have presented an unreasonable risk to the study patient as a result of his/her participation in this clinical trial, may have made the patient’s participation unreliable or may have interfered with study assessments. The specific justification for patients excluded under this criterion was to be noted in study documents (chart notes and eCRF).History of substance and/or alcohol abusePlanned major surgical procedure during the patient’s participation in this studyExposure to another systemic or topical investigative drug (monoclonal antibodies as well as small molecules) within a certain time period before visit 1 (screening), as follows: an interval of less than 6 months or <5 pharmacokinetic (PK) half-lives for investigative monoclonal antibodies, whichever was longer, and an interval of fewer than 30 days or <5 PK half-lives, whichever was longer, for investigative small moleculesHad used any of the following treatments within 4 weeks before the screening visit:Systemic immunosuppressive/immunomodulating drugs (for example, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon-gamma, Janus kinase inhibitors, azathioprine, methotrexate, hydroxychloroquine, dapsone, sulfasalazine and colchicine)Intralesional corticosteroid injections and cryotherapyPhototherapy, including tanning bedsNaltrexone or other opioid antagonistsGabapentin, pregabalin or thalidomideStarted to use the following treatments or changed the dose of the following treatments in 3 months before the screening visit or expected the dose of the following treatments would be changed throughout the study:Paroxetine, fluvoxamine or other selective serotonin reuptake inhibitors (SSRIs)Serotonin and norepinephrine reuptake inhibitors (SNRIs)Amitriptyline or other tricyclic or tetracyclic antidepressantsPrevious treatment with biologic medicines within the following timeframe:Any cell-depleting agents including, but not limited to, rituximab: within 6 months before the screening visitOmalizumab: within 5 months before screening visitOther immunomodulatory biologics: within 5 half-lives (if known) or 16 weeks before the screening visit, whichever was longerInitiation of treatment with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, menthol, polidocanol or filaggrin degradation products during the screening period (patients could continue using stable doses of such moisturizers if initiated before the screening visit)Initiation of treatment with TCS/TCI (any potency) during the screening period or treatment with high-potency or super-potent TCS/TCI during the screening periodFor patients who were on a stable regimen of TCS/TCI (maintain same medicine, same dose from 2 weeks before screening visit) at the screening visit:Application of TCS/TCI on fewer than 6 days during the 7 days immediately preceding randomizationApplication of TCS/TCI of incorrect potency within 7 days before day 1 (correct application was low potency if on low potency at screening visit and medium potency if on medium or higher potency at screening visit)Treatment with a live (attenuated) vaccine within 4 weeks before the screening visitFor patients who had vaccination with live, attenuated vaccines planned during the study (based on national vaccination schedule/local guidelines), it was determined, after consultation with a physician, whether the administration of vaccine could be postponed until after the end of study or preponed to before the start of the study, without compromising the health of the patient.Patients for whom administration of live (attenuated) vaccine could be safely postponed were eligible to enroll in the study.Patients who had their vaccination preponed could enroll in the study only after a gap of 4 weeks after administration of the vaccine.Planned or anticipated use of any prohibited medications and procedures during screening and study treatment periodParticipation in a prior dupilumab clinical study, treated in the past with dupilumab or prior use of biologics for PNFor patients without history of HIV infection before screening visit, positive HIV serology at screening; for patients with history of HIV infection, CD4Patients with any of the following results at screening:Positive (or indeterminate) HBs AgPositive total HBc Ab confirmed by positive HBV DNAPositive HCV Ab confirmed by positive HCV RNA