Serious Infections: Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Malignancies: Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.
Other Serious Adverse Reactions: Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.
Plaque Psoriasis: HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
Hidradenitis Suppurativa: HUMIRA is indicated for the treatment of adult patients with moderate to severe hidradenitis suppurativa.
Psoriatic Arthritis: HUMIRA is indicated, alone or in combination with non-biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis.
I’m Dr. Jennifer Cather. Today I’d like to talk to you about HUMIRA, the first and only FDA-approved treatment for moderate to severe hidradenitis suppurativa, or HS. HUMIRA is a subcutaneous injectable biologic that targets TNF-α, a key cytokine and source of inflammation in many immune-mediated diseases, including HS. The relationship between these pharmacodynamic activities and the mechanism or mechanisms by which HUMIRA exerts its clinical effect is unknown.
The safety and efficacy of HUMIRA was studied in PIONEER I and PIONEER II, the first and only completed Phase 3, randomized, placebo-controlled trials in HS. These were 36-week, double-blind trials with 2 treatment periods: A and B. The patient population was 633 adult patients with lesions, 1 of which was Hurley stage II or Hurley stage III. The Hurley staging system is a widely used classification. The total abscess and inflammatory nodule count was at least 3 at the baseline visit.
In Period A, which was baseline to Week 12, patients in both studies received HUMIRA or control by subcutaneous injection. Concomitant oral antibiotic use was allowed in PIONEER II. During the trial, at Week 0 dosing started at 160 mg, then 80 mg at Week 2, and finally a maintenance dose at Week 4 of 40 mg every week through Week 11. The primary endpoint was the proportion of patients achieving HiSCR, which was the measure of clinical response in these trials, at Week 12. HiSCR stands for Hidradenitis Suppurativa Clinical Response.
Clinical response required: At least a 50% reduction in total abscess and inflammatory nodule count relative to baseline, with no increase in abscess count AND no increase in draining fistula count. Period B explored the safety and efficacy of different maintenance regimens over 24 weeks. Patients were instructed to discontinue from Period B and enter the open-label extension—or OLE—study if they achieved HiSCR in Period A and subsequently had loss of response, or if they did not achieve HiSCR and experienced worsening or absence of improvement on or after Week 16.
170 and 116 patients completed Period B in PIONEER I and PIONEER II, respectively. 79% of patients entered the OLE. In PIONEER I, a significantly greater proportion of HUMIRA-treated patients achieved clinical response vs control patients at Week 12: 42% of HUMIRA-treated patients vs 26% of control patients. In PIONEER II, more than twice as many patients treated with HUMIRA achieved clinical response vs control patients at Week 12: 59% of HUMIRA-treated patients vs 28% of control patients.
Here you can see what clinically meaningful improvement may look like for your patients with moderate to severe HS. And in my experience using various HS treatments, moderate patients who start on therapy before their disease becomes severe do better. The safety profile of HUMIRA in patients with HS was consistent with the known safety profile of HUMIRA.
Here you can see the treatment-emergent adverse events in PIONEER I during Period A. And here are the treatment-emergent adverse events in PIONEER II during Periods A and B.
Adverse reaction rates observed in clinical trials may not predict the rates observed in a broader patient population in clinical practice. This is because clinical trials are conducted under controlled conditions.
So to sum up: HUMIRA studies PIONEER I and II are the first and only completed Phase 3 clinical trials in HS, a disease that in moderate to severe stages can be progressive and debilitating. In these trials, many patients taking HUMIRA achieved clinically meaningful improvement, or HiSCR, with a safety profile that was consistent with the known safety profile of HUMIRA.
HUMIRA for moderate to severe HS is a weekly subcutaneous injectable. The way that HUMIRA treats HS is different. It targets a key source of inflammation and is the first and only FDA-approved treatment for HS.
Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue HUMIRA if a patient develops a serious infection or sepsis.
Reported infections include:
Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including HUMIRA. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.
For full Prescribing Information, visit rxabbvie.com/pdf/humira.pdf
Reference: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc.