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VBCR - December 2016, Vol 5, No 6 - Drug Update
Loretta Fala

Psoriatic arthritis is an inflammatory form of arthritis that is characterized by swelling, stiffness, and pain and is often accompanied by skin and nail psoriasis; it can affect any joint, including fingers and toes.1 Psoriatic arthritis affects an estimated 0.3% to 1% of the US population (>3 million people).2 Furthermore, as many as 30% of individuals with psoriasis will have psoriatic arthritis.1

Ankylosing spondylitis, a type of inflammatory arthritis, is a painful, progressively debilitating disease that affects the spine, vertebrae, cartilage, and joints—particularly joints in the sacroiliac area where the base of the spine joins the pelvis.3 The disease is also associated with uveitis (eye inflammation), compression fractures, and, in some cases, heart and lung problems.4 Nearly 500,000 people in the United States have ankylosing spondylitis.5

The chronic pain, fatigue, and physical limitations associated with these inflammatory diseases affect the patient’s health-related quality of life and impose a substantial societal burden.6 Early diagnosis and treatment of these conditions are crucial to reduce inflammation, prevent joint damage, and relieve pain.5

Cosentyx Approved for Psoriatic Arthritis and Ankylosing Spondylitis

On January 15, 2016, the US Food and Drug Administration (FDA) approved secukinumab (Cosentyx; Novartis), an interleukin (IL)-17A antagonist, for the treatment of patients with active psoriatic arthritis or with active ankylosing spondylitis.7 Secukinumab is the first IL-17A antagonist to be FDA approved for these 2 conditions.7

Secukinumab was initially approved by the FDA in January 2015 for the treatment of patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.8,9

Mechanism of Action

IL-17A is a naturally occurring cytokine that plays a role in the body’s inflammatory and immune responses.9 Secukinumab, a recombinant human immunoglobulin G1 monoclonal antibody, selectively binds to IL-17A and inhibits its interaction with the IL-17 receptor, thereby blocking the release of proinflammatory cytokines.9

Dosing and Administration

For patients with psoriatic arthritis and coexisting moderate-to-severe plaque psoriasis, the recommended dosage of secukinumab is 300 mg via subcutaneous injection at weeks 0, 1, 2, 3, and 4, followed by 300 mg every 4 weeks. A 150-mg dose of secukinumab may be acceptable for some patients.

For other patients with psoriatic arthritis, secukinumab is administered with or without a loading dosage; when administered with a loading dosage, secukinumab should be given at 150 mg at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter; when administered without a loading dose, secukinumab should be administered at 150 mg every 4 weeks. If the patient’s active psoriatic arthritis persists, a dose of secukinumab 300 mg should be considered.9

For patients with ankylosing spondylitis, secukinumab is administered with or without a loading dosage. The recommended dosage of secukinumab when administered with a loading dose is 150 mg at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter; when secukin­umab is administered without a loading dose, the recommended dosage is 150 mg every 4 weeks.9

Secukinumab is available in 3 injection forms, including a 150-mg/mL solution in a single-use Sensoready pen; a 150-mg/mL solution in a single-use prefilled syringe; and a 150-mg, lyophilized powder in a single-use vial (reconstitution for healthcare professional use only).9

Pivotal Clinical Trials

Psoriatic Arthritis

The FDA approval of secukinumab for the treatment of patients with active psoriatic arthritis was based on 2 randomized, double-blind, placebo-controlled clinical trials—FUTURE 1 and FUTURE 2—involving 1003 adults with active disease.9-11 Patients had psoriatic arthritis for at least 5 years before clinical trial enrollment. The primary end point in both studies was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 24.9-11

An ACR20 response is a 20% improvement in tender and swollen joint counts and a 20% improvement in 3 of the 5 remaining ACR core set measures (patient and physician global assessments, pain, disability, others). An ACR50 response represents a 50% improvement in both measures; an ACR70, a 70% improvement in both measures.

In the FUTURE 1 study with 606 patients, those who received secukin­umab at the 150-mg or the 75-mg dose had a significantly higher ACR20 response rate at week 24 versus placebo; 50% of patients who received secukinumab 150 mg and 50.5% of patients who received secukinumab 75 mg achieved an ACR20 response versus 17.3% of patients who received placebo (P <.001; both results vs placebo).10

In the FUTURE 2 study, secukin­umab 150 mg or 300 mg achieved a greater clinical response in ACR20, ACR50, and ACR70 compared with placebo at week 24 (Table 1).9,11,12

Table

Ankylosing Spondylitis

The FDA approval of secukinumab for the treatment of patients with ankylosing spondylitis was based on the safety and efficacy data from the MEASURE 1 and MEASURE 2 studies—2 randomized, double-blind, placebo-controlled studies involving 590 patients.9,13 In both studies, the primary end point was the percentage of patients who achieved an Assessment of SpondyloArthritis International Society (ASAS)20 response at week 16.13

ASAS20 was defined as an improvement of at least 20%, and absolute improvement of at least 1 unit (on a 10-unit scale) in at least 3 of the 4 main ASAS domains, with no worsening by ≥20% in the remaining domain. Similarly, ASAS40 was defined as an improvement of at least 40% and absolute improvement of at least 1 unit (on a 10-unit scale) in at least 3 of the 4 main ASAS domains, with no worsening by ≥20% in the remaining domain.13

In the MEASURE 1 study with 371 patients, 61% of the patients who received secukinumab 150 mg achieved an ASAS20 response at week 16 compared with 29% of patients who received placebo at week 16 (P <.001).9,13

These results were nearly identical to the MEASURE 2 clinical trial that included 219 patients: those who received secukinumab 150 mg achieved significantly greater improvements in ASAS20 and ASAS40 response rates than patients who received placebo at week 16 (Table 2).9,13

Table

Adverse Events

The safety of secukinumab was evaluated in 4 clinical trials that included 3430 patients, 1641 of whom were exposed to the drug for at least 1 year. The most common adverse reactions that were reported by >1% of patients who received secukinumab 300 mg or 150 mg were nasopharyngitis (11.4% and 12.3%, respectively), diarrhea (4.1% and 2.6%, respectively), and upper respiratory tract infection (2.5% and 3.2%, respectively).9

The safety profiles from the 2 psoriatic arthritis studies with 1003 patients (703 patients received secukinumab) and from the 2 ankylosing spondylitis studies with 590 patients (394 patients received secukinumab) were consistent with the plaque psoriasis study.

In the psoriatic arthritis clinical trials, adverse events that occurred in ≥2% of patients who received secukin­umab and at a greater incidence than placebo were nasopharyngitis, upper respiratory tract infection, headache, nausea, and hypercholesterolemia. In the 2 ankylosing spondylitis clinical trials, adverse events that occurred in ≥2% of patients who received secukin­umab and more frequently than placebo were nasopharyngitis, nausea, and upper respiratory tract infection.9

Contraindications

Secukinumab is contraindicated in patients with a serious hypersensitivity reaction to secukinumab or to any of its excipients.9

Warnings and Precautions

Secukinumab may increase the risk for infections, and some serious infections have been reported.9 Therefore, caution should be exercised when considering the use of secukinumab for patients with a chronic infection or a history of recurring infection. If a patient has a serious infection, secukin­umab should be discontinued until the infection is resolved.9

Before initiating secukinumab treatment, patients should be evaluated for tuberculosis; secukinumab should not be administered to patients with active tuberculosis. Patients should be closely monitored for signs of active tuberculosis during and after treatment with secukinumab.9

Cases of inflammatory bowel disease, including serious inflammatory bowel disease, have occurred in patients who received secukinumab; caution should be used when prescribing secukinumab to patients with this disease.9

Anaphylactic reactions have occurred with secukinumab therapy. If a patient has an anaphylactic reaction or other serious allergic reactions, secukin­umab should be immediately discontinued, and appropriate treatment should be initiated.9

Studies assessing drug interactions with secukinumab have not been conducted. Patients who receive secu­kinumab should not receive live vaccinations.9

Use in Specific Populations

Because it is not known whether secukinumab is excreted in human milk, caution is advised when secukin­umab is administered to a nursing woman.9

Of the 3430 patients with plaque psoriasis who received secukinumab in clinical trials, 230 patients were aged ≥65 years and 32 were aged ≥75 years.9 No differences in the safety or efficacy of secukinumab were observed between patients in these age-groups and younger patients; however, the number of older patients was insufficient to assess a definitive difference between the 2 age-groups.9

Conclusion

With the 2 FDA approvals for secu­kinumab for the treatment of patients with active psoriatic arthritis or active ankylosing spondylitis, secukinumab became the first IL-17A antagonist approved for these conditions.

In clinical trials, secukinumab demonstrated significant improvements in response rates in patients with psoriatic arthritis or ankylosing spondylitis. Given its novel mechanism of action—targeting the proinflammatory cytokines implicated in these 2 debilitating conditions—secukinumab is an important therapeutic option for improving outcomes in patients with psoriatic arthritis or ankylosing spondylitis.

Copyright © 2016 American Health & Drug Benefits. Used with permission.




References

  1. National Psoriasis Foundation. About psoriatic arthritis. www.psoriasis.org/about-psoriatic-arthritis. Accessed August 22, 2016.
  2. Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64(suppl 2):ii14-ii17.
  3. Spondylitis Association of America. Ankylosing spondylitis. www.spondylitis.org/About-Spondylitis/Ankylosing-Spondylitis. Accessed August 22, 2016.
  4. Mayo Clinic staff. Diseases and conditions: ankylosing spondylitis: definition. February 11, 2014. www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/basics/definition/con-20019766. Accessed August 22, 2016.
  5. Arthritis Foundation. What is ankylosing spondylitis? www.arthritis.org/about-arthritis/types/ankylosing-spondylitis/what-is-ankylosing-spondylitis.php. Accessed August 22, 2016.
  6. Lee S, Mendelsohn A, Sarnes E. The burden of psoriatic arthritis: a literature review from a global health systems perspective. P T. 2010;35:680-689.
  7. Novartis. Novartis receives two new FDA approvals for Cosentyx (secukinumab) to treat patients with ankylosing spondylitis and psoriatic arthritis. Press release. January 15, 2016. www.pharma.us.novartis.com/news/media-releases/novartis-receives-two-new-fda-approvals-cosentyxr-secukinumab-treat-patients. Accessed August 22, 2016.
  8. US Food and Drug Administration. FDA approves new psoriasis drug Cosentyx. Press release. January 21, 2015. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm430969.htm. Accessed August 22, 2016.
  9. Cosentyx (secukinumab) for injection [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; January 2016.
  10. Mease PJ, McInnes IB, Kirkham B, et al; for the FUTURE 1 Study Group. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329-1339.
  11. McInnes IB, Mease PJ, Kirkham B, et al; for the FUTURE 2 Study Group. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;386:1137-1146.
  12. Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38:727-735.
  13. Baeten D, Sieper J, Braun J, et al; for the MEASURE 1 Study Group; MEASURE 2 Study Group. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373:2534-2548.
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