Effective Date

Date of Origin 

07-01-2025            

10-01-2024

Spevigo®

(spesolimab-sbzo)

Prefilled syringe for subcutaneous injection

Treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients 12 years of age and older and weighing at least 40 kg

1

Generalized Pustular Psoriasis

Generalized pustular psoriasis (GPP) is a rare inflammatory skin condition characterized by recurrent pustules that vary in size and severity. Approximately 46% of patients with GPP have plaque psoriasis, however GPP is a distinctly different disease from plaque psoriasis. Both adults and children are affected by GPP with severity ranging from mild to severe with each flare. Estimates of GPP prevalence vary between 1.8 and 124 per million people. GPP pathogenesis primarily involves abnormal activation of the interleukin (IL)-36 pathway of the innate immune system, with secondary contributions from the adaptive immune system.(2,7)

GPP has two major clinical presentations, acute GPP (aka generalized pustular psoriasis of von Zumbusch) and generalized annular pustular psoriasis. Acute GPP is characterized by the abrupt development of widespread, painful erythematous patches or thin plaques that rapidly become studded with numerous pinhead-sized sterile pustules. Some pustules will then coalesce resulting in larger collections referred to as “lakes of pus.” Acutely affected patients experience recurrent and sudden onset flare ups. These patients present systemically ill with a high-grade fever, pain, arthralgias, widespread pustules and often times systemic inflammation.(2,7) Patients may also experience leukocytosis, malaise, and at times extracutaneous organ involvement, such as sepsis and/or renal, hepatic, respiratory, and heart failure, which can be life threatening. Due to the rarity of the disease, there is very little consensus on the definition and different phenotypes.(2) Generalized annual pustular psoriasis presents as a recurring, subacute eruption characterized by the development of annular or figurate erythematous plaques with peripheral pustules and scale. Pustules expand out over hours to days. Acute GPP and generalized annular pustular psoriasis pustules typically resolve within a few days, leaving erythema and extensive scaling.(3) 

GPP flares can occur multiple times per year or may not occur for years at a time. Flares are often provoked, with withdrawal of systemic corticosteroids being the most common precipitating factor. Other precipitating factors include infections, sunlight, pregnancy, menstruation, and numerous systemic medications. Other medications known to precipitate flares include lithium, progesterone, infliximab, adalimumab, and apremilast. Flares typically last between 2 to 5 weeks but some flares may last for up to 3 months. Patients do not always achieve completely clear skin between flares of GPP. Roughly 30% of patients may have persistent pustular lesions.(2,3)

GPP is diagnosed using a combination of patient history of symptoms, physical examination, skin biopsy, and labs. The diagnosis of GPP is suspected in patients that present with widespread pustules arising on erythematous skin.(4,5) Treatment consists of a combination of phototherapy and systemic and/or topical treatments and can be broken down into supportive care and long-term management. Initial management usually consists of systemic therapy to rapidly stabilize acute flares. The ADA recommends Spevigo, biologics (e.g., Otezla, Cosentyx, Taltz), cyclosporine, methotrexate, or acitretin and more than one agent may be used at a time.(6,7) 

Physicians specializing in psoriatic diseases from the Medical Board of the National Psoriasis Foundation formulated the following consensus statements as a guide in GPP management:(7,8)

• Therapeutic developments have been focused on modulating the aberrantly increased interleukin 36 signaling in GPP. 
• Spesolimab is the first US Food and Drug Administration-approved treatment that is highly effective in the treatment of GPP flares in adults.
• Timely access to approved therapies is critical to reducing morbidity and mortality in patients presenting with GPP.

Efficacy

A randomized, double-blind, placebo-controlled study (Study Effisayil-2) [NCT04399837] evaluated the efficacy and safety of Spevigo for subcutaneous administration in adults and pediatric subjects (12 years of age and older and weighing at least 40 kg) with a history of at least two GPP flares of moderate-to-severe intensity in the past. Subjects were randomized if they had a Generalized Pustular Psoriasis Physician Global Assessment GPPPGA total score of 0 or 1 at screening and randomization. Subjects were required to discontinue systemic and topical therapy for GPP prior to or at randomization. These subjects must have had a history of flaring while on concomitant treatment for GPP or a history of flaring upon dose reduction or discontinuation of these concomitant medications. A total of 123 subjects were randomized (1:1:1:1) to one of four treatment arms:(1)

• SPEVIGO: 600 mg subcutaneous loading dose (LD) followed by 300 mg subcutaneously every 4 weeks
• SPEVIGO: 600 mg subcutaneous LD followed by 300 mg subcutaneously every 12 weeks
• SPEVIGO: 300 mg subcutaneous LD followed by 150 mg subcutaneously every 12 weeks
• Placebo: subcutaneous LD followed by subcutaneous treatment every 4 weeks

Despite alternative dosing being used in this trial, (600 mg LD dose followed by 300 mg every 12 weeks dosage and a 300 mg LD followed by 150 mg every 12 weeks), these dosages are not approved. The recommended dosage of Spevigo for treatment of GPP when not experiencing a flare is a subcutaneous LD of 600 mg followed by 300 mg subcutaneously, administered every 4 weeks. The study population was 38% male and 62% female. The mean age was 40 years old (range: 14 to 75 years) with 8 (7%) pediatric subjects (2 per treatment arm); 64% of subjects were Asian and 36% were White. For ethnicity, 6% of subjects identified as Hispanic or Latino. Subjects included in the study had a GPPPGA pustulation sub score of 1 (28%) or 0 (72%), and subjects had a GPPPGA total score of 1 (86%) or 0 (14%). At the time of randomization, 75% of subjects were treated with systemic therapy for GPP, which was discontinued at the start of the randomized study treatment.

Subjects who experienced a GPP flare were eligible to receive up to two open-label intravenous doses of 900 mg Spevigo. Two subjects in the subcutaneous Spevigo 600 mg LD/300 mg every 4 weeks arm and 15 subjects in the placebo arm received intravenous Spevigo for treatment of GPP flare. The primary endpoint of the study was the time to the first GPP flare up to Week 48 (defined by a GPPPGA pustulation sub score of greater than or equal to 2 and an increase in GPPPGA total score by greater than or equal to 2 from baseline). The key secondary endpoint was the occurrence of at least one GPP flare up to Week 48.(1)

Spevigo significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. In the trial with 123 patients, no flares were observed after Week 4 of treatment in the high dose group.(1)

Safety

Spevigo is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in Spevigo.(1)

1

Spevigo prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. March 2024.

2

Choon, S.E., Navarini, A.A. & Pinter, A. Clinical Course and Characteristics of Generalized Pustular Psoriasis. Am J Clin Dermatol 23 (Suppl 1), 21–29 (2022). https://doi.org/10.1007/s40257-021-00654-z.

3

Choon SE, Lai NM, Mohammad NA, et al. Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia. Int J Dermatol 2014; 53:676.

4

Ly K, Beck KM, Smith MP, Thibodeaux Q, Bhutani T. Diagnosis and screening of patients with generalized pustular psoriasis. Psoriasis (Auckl). 2019 Jun 20;9:37-42. doi: 10.2147/PTT.S181808.

5

Fujita, H., Gooderham, M. & Romiti, R. Diagnosis of Generalized Pustular Psoriasis. Am J Clin Dermatol 23 (Suppl 1), 31–38 (2022). https://doi.org/10.1007/s40257-021-00652-1.

6

Falto-Aizpurua LA, Martin-Garcia RF, Carrasquillo OY, et al. Biological therapy for pustular psoriasis: a systematic review. Int J Dermatol 2020; 59:284.

7

Armstrong AW, Elston CA, Elewski BE, et al. Generalized pustular psoriasis: A consensus statement from the National Psoriasis Foundation. J Am Acad Dermatol. 2024;90(4):727-730. doi:10.1016/j.jaad.2023.09.080

8

Pustular psoriasis: Treatment. https://www.aad.org/public/diseases/psoriasis/treatment/medications/pustular

Spevigo

spesolimab-sbzo subcutaneous soln pref syr

150 MG/ML

M ; N ; O ; Y

N

Spevigo

spesolimab-sbzo subcutaneous soln pref syr

150 MG/ML

2

Syringes

28

DAYS

Spevigo

spesolimab-sbzo subcutaneous soln pref syr

150 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Spevigo

spesolimab-sbzo subcutaneous soln pref syr

150 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
   2. BOTH of the following:
      1. ONE of the following:
         1. The patient has a diagnosis of generalized pustular psoriasis (GPP) AND ALL of the following:
            1. The patient has moderate to severe GPP AND
            2. The patient has a history of 2 or more flares AND
            3. The patient is NOT currently experiencing an acute flare OR
         2. The patient has another FDA labeled indication for the requested agent OR
      2. If the patient has an FDA labeled indication, then ONE of the following:
         1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
         2. There is support for using the requested agent for the patient’s age AND
2. If the patient has a diagnosis of GPP, then the patient weighs greater than or equal to 40 kg AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. ONE of the following:
   1. The patient does NOT have active or latent tuberculosis (TB) OR
   2. The patient has latent tuberculosis (TB) and the patient has begun or completed therapy for latent TB prior to initiating with the requested agent AND
5. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table):
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (copy of support required, i.e., clinical trials, phase III studies, guidelines) AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months 

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table):
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (copy of support required, i.e., clinical trials, phase III studies, guidelines) AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months 

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QL

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval:  up to 12 months

Note: If patient is NOT transitioning from IV to SC maintenance: Approve Spevigo loading dose for 1 month, then maintenance dose can be approved for the remainder of 12 months. Patient IS transitioning from IV to SC maintenance dosing due to a recent flare: Approve 12 months for maintenance therapy.

Agents NOT to be used Concomitantly

Abrilada (adalimumab-afzb)
Actemra (tocilizumab)
Adalimumab
Adbry (tralokinumab-ldrm)
Amjevita (adalimumab-atto)
Arcalyst (rilonacept)
Avsola (infliximab-axxq)
Benlysta (belimumab)
Bimzelx (bimekizumab-bkzx)
Cibinqo (abrocitinib)
Cimzia (certolizumab)
Cinqair (reslizumab)
Cosentyx (secukinumab)
Cyltezo (adalimumab-adbm)
Dupixent (dupilumab)
Ebglyss (lebrikizumab-lbkz)
Enbrel (etanercept)
Entyvio (vedolizumab)
Fasenra (benralizumab)
Hadlima (adalimumab-bwwd)
Hulio (adalimumab-fkjp)
Humira (adalimumab)
Hyrimoz (adalimumab-adaz)
Idacio (adalimumab-aacf)
Ilaris (canakinumab)
Ilumya (tildrakizumab-asmn)
Imuldosa (ustekinumab-srlf)
Inflectra (infliximab-dyyb)
Infliximab
Kevzara (sarilumab)
Kineret (anakinra)
Leqselvi (deuruxolitinib)
Litfulo (ritlecitinib)
Nemluvio (nemolizumab-ilto)
Nucala (mepolizumab)
Olumiant (baricitinib)
Omvoh (mirikizumab-mrkz)
Opzelura (ruxolitinib)
Orencia (abatacept)
Otezla (apremilast)
Otulfi (ustekinumab-aauz)
Pyzchiva (ustekinumab-ttwe)
Remicade (infliximab)
Renflexis (infliximab-abda)
Riabni (rituximab-arrx)
Rinvoq (upadacitinib)
Rituxan (rituximab)
Rituxan Hycela (rituximab/hyaluronidase human)
Ruxience (rituximab-pvvr)
Saphnelo (anifrolumab-fnia)
Selarsdi (ustekinumab-aekn)
Siliq (brodalumab)
Simlandi (adalimumab-ryvk)
Simponi (golimumab)
Simponi ARIA (golimumab)
Skyrizi (risankizumab-rzaa)
Sotyktu (deucravacitinib) 
Spevigo (spesolimab-sbzo) subcutaneous injection
Stelara (ustekinumab)
Steqeyma (ustekinumab-stba)
Taltz (ixekizumab)
Tezspire (tezepelumab-ekko)
Tofidence (tocilizumab-bavi)
Tremfya (guselkumab)
Truxima (rituximab-abbs)
Tyenne (tocilizumab-aazg)
Tysabri (natalizumab)
Ustekinumab
Velsipity (etrasimod)
Wezlana (ustekinumab-auub)
Xeljanz (tofacitinib)
Xeljanz XR (tofacitinib extended release)
Xolair (omalizumab)
Yesintek (ustekinumab-kfce)
Yuflyma (adalimumab-aaty)
Yusimry (adalimumab-aqvh)
Zeposia (ozanimod)
Zymfentra (infliximab-dyyb)