U.S. Food and Drug Administration (FDA)-Approved Indications

Guselkumab is available as Tremfya (Janssen Biotech, Inc). Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines (Janssen Biotech, 2020).

Labeled warning and precautions include hypersensitivity reactions and infections. Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of Tremfya. Some cases required hospitalization. In addition, Tremfya may increase the risk of infection. In clinical trials in subjects with plaque psoriasis, infections occurred in 23% of subjects in the Tremfya group versus 21% of subjects in the placebo group through 16 weeks of treatment. Upper respiratory tract infections, gastroenteritis, tinea infections, and herpes simplex infections occurred more frequently in the Tremfya group than in the placebo group. A similar risk of infection was seen in placebo-controlled trials in subjects with psoriatic arthritis.

The label recommends evaluating patients for tuberculosis (TB) infection prior to initiating treatment. The prescribing information states to "initiate treatment of latent TB prior to administering Tremfya. In clinical trials, 105 subjects with plaque psoriasis and 71 subjects with psoriatic arthritis with latent TB who were concurrently treated with Tremfya and appropriate TB prophylaxis did not develop active TB. Monitor patients for signs and symptoms of active TB during and after Tremfya treatment. Consider anti-TB therapy prior to initiating Tremfya in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Do not administer Tremfya to patients with active TB infection" (Janssen Biotech, 2020).

The most common (1% or more) adverse reactions associated with Tremfya include upper respiratory infections, headache, injection site reactions, arthralgia, bronchitis, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.

Plaque Psoriasis

In July 2017, the U.S. Food and Drug Administration (FDA) approved Tremfya (guselkumab) for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Guselkumab, an interleukin-23 (IL-23) blocker, is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines (Johnson & Johnson, 2017).

Tremfya received FDA approval based on results from Phase 3, multicenter, randomized, double-blind trials (VOYAGE 1, VOYAGE 2, and NAVIGATE studies). In VOYAGE 1 and VOYAGE 2, 1443 subjects, 18 years and older, were randomized to either Tremfya (100 mg at Weeks 0 and 4 and every 8 weeks thereafter), placebo or adalimumab (80 mg at Week 0 and 40 mg at Week 1, followed by 40 mg every other week thereafter). At 16 weeks, at least seven out of ten Tremfya-treated patients achieved at least 90 percent clearer skin, and more than 80 percent demonstrated cleared or almost cleared skin. Improvements were also demonstrated in psoriasis involving the scalp and in symptoms of plaque psoriasis including itch, pain, stinging, burning and skin tightness. Treatment resulted in clearer skin that lasted, as nearly nine out of ten patients who achieved PASI 90 at week 28 maintained that response at week 48. At week 24, more than seven out of ten patients treated with Tremfya reported at least 90 percent clearer skin compared with more than four out of ten patients treated with adalimumab (Janssen Biotech, 2017a, 2017b).

NAVIGATE findings demonstrated the effectiveness of Tremfya in patients who had an inadequate response to treatment with ustekinumab. NAVIGATE evaluated the efficacy of 24 weeks of treatment with Tremfya in subjects (N=268) who had not achieved an adequate response, defined as IGA ≥2 at Week 16 after initial treatment with ustekinumab (dosed 45 mg or 90 mg according to the subject’s baseline weight at Week 0 and Week 4). These subjects were randomized to either continue with ustekinumab treatment every 12 weeks or switch to Tremfya 100 mg at Weeks 16, 20, and every 8 weeks thereafter. In subjects with an inadequate response (IGA ≥2 at Week 16 to ustekinumab), greater proportions of subjects on Tremfya compared to ustekinumab achieved an IGA score of 0 or 1 with a ≥2 grade improvement at Week 28 (31% vs 14%, respectively; 12 weeks after randomization) (Janssen Biotech, 2017a).

Psoriatic Arthritis

In July 2020, the U.S. FDA approved Tremfya (guselkumab) for the treatment of adult patients with active psoriatic arthritis (PsA), a chronic progressive disease characterized by painful joints and skin inflammation. FDA approval was based on the results from two pivotal Phase 3 clinical trials (DISCOVER-1 and DISCOVER-2), which were randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of guselkumab in 1,120 adult patients with active PsA who had inadequate response to standard therapies (Janssen, 2020).

Deodhar et al (2020) state that guselkumab, a specific inhibitor of interleukin-23 (IL-23) via IL-23 p19 subunit binding, significantly improved psoriatic arthritis signs and symptoms with an acceptable safety profile in a phase 2 trial. Thus, the authors conducted a multicenter, double-blind, randomized, placebo-controlled, phase 3 trial (DISCOVER-1) to evaluate guselkumab in adults with active psoriatic arthritis. Eligibility criteria included inadequate response to or intolerance of standard treatment, including at least 4 months of apremilast, at least 3 months of non-biologic disease-modifying antirheumatic drugs (DMARDs), or at least 4 weeks of non-steroidal anti-inflammatory drugs for psoriatic arthritis. About 30% of study participants could have previously received one or two TNF inhibitors. There were 381 patients randomly assigned (1:1:1) to subcutaneous guselkumab 100 mg every 4 weeks (n=128), guselkumab 100 mg at weeks 0, 4 and then every 8 weeks (n=127), or placebo (n=126). 362 patients continued study treatment up to week 24. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) at week 24 in all patients per assigned treatment group using non-responder imputation. Safety was assessed in all patients per treatment received. The primary endpoint was met: ACR20 at week 24 was achieved by significantly greater proportions of patients in the guselkumab every 4 weeks group and every 8 weeks group than in the placebo group, with percentage differences versus placebo of 37% for the every 4 weeks group and 30% for the every 8 weeks group (both p<0·0001). Serious adverse events up to week 24 occurred in no patients receiving guselkumab every 4 weeks, four (3%) patients receiving guselkumab every 8 weeks, and five (4%) patients receiving placebo. Up to week 24, one patient in the placebo group died from cardiac failure and two had serious infections; no guselkumab-treated patient died or had serious infections. The authors concluded that guselkumab demonstrated a favourable benefit-risk profile and might be an effective treatment option for patients with active psoriatic arthritis.

Mease et al (2020) conducted a multicenter, phase 3, double-blind, placebo-controlled study (DISCOVER-2) to evaluate guselkumab in biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was ACR20 response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. A total of 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57-70]) and every 8 weeks group (159 [64%] of 248 [58-70]) than in the placebo group (81 [33%] of 246 [27-39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22-39] for the every 4 weeks group and 31% [23-40] for the every 8 weeks group; both p<0·0001). Up to week 24, serious adverse events occurred in eight (3%) of 245 patients receiving guselkumab every 4 weeks (three serious infections), three (1%) of 248 receiving guselkumab every 8 weeks (one serious infection), and seven (3%) of 246 receiving placebo (one serious infection). No deaths occurred. The authors concluded that guselkumab was efficacious and demonstrated an acceptable benefit-risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics.

Appendix

Examples of Clinical Reasons to Avoid Pharmacologic Treatment with Methotrexate, Cyclosporine, Acitretin, or Leflunomide

Prescriber Specialties

This medication must be prescribed by or in consultation with

of the following:

Criteria for Initial Approval

Aetna considers guselkumab (Tremfya)

Plaque psoriasis (PsO)

Psoriatic arthritis (PsA)

Member has mild to moderate disease and meets

of the following criteria:

Member has severe disease.

Aetna considers all other indications as experimental and investigational

.

Continuation of Therapy

Aetna considers continuation of guselkumab (Tremfya) therapy medically necessary for the following indications:

Plaque psoriasis (PsO)

For all adult members (including new members) who are using the requested medication for moderate to severe plaque psoriasis and who achieve or maintain positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when

of the following is met:

Psoriatic arthritis (PsA)

For all adult members (including new members) who are using the requested medication for psoriatic arthritis and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in

of the following from baseline:

* If the screening test for TB is positive, there must be further testing to confirm there is no active disease. Do not administer the requested medication to members with active TB infection. If there is latent disease, TB treatment must be started before initiation of the requested medication.