would be double the cost of effectively clearing one biologically naive subject with standard biologic dosing (Figure 3).
Switching to Another Biologic Approach Cost Considerations
Studies evaluating switching to another biologic approach reporting clearance as PASI 100 or PGA 0 were identified for infliximab and guselkumab only.15,16 Similar to dose escalation approach, the number of subjects in the study and percentage of patients achieving clearance were used to determine NNT to achieve clearance in one additional patient (Figure 1). We assumed that the baseline cost on the first biologic would equal the cost of the switched biologic except the additional cost of loading dose of the new biologic. To determine the additional cost with this approach, we needed to estimate cost of the new biologic loading dose. For infliximab, the loading dose of 5 mg/ kg is administered at weeks 0, 2, and 6. We used the price of reconstituted 100 mg intravenous infliximab solution ($1,167) obtained from Medi-Span Price Rx,9 and the average weight was assumed to be 80 kg, which would require a 400 mg infliximab dose. The cost/unit of medication ($1,167*4 = $4,668) was multiplied by the number of medication units (three) administered during loading period of infliximab: $4,668*3 = $14,004 to estimate cost of the new biologic loading dose. Multiplying this cost by the NNT provides additional cost required to effectively clear one more patient not achieving complete clearance on initial biologic: $14,004 x 6.3 = $88,225 when switching to infliximab (Figure 4).
In the study evaluating switching to guselkumab, patients were administered guselkumab at weeks 0 and 4 during the loading phase after an inadequate response to ustekinumab. We multiplied the cost/unit of medication ($10,859) by the number of medication units (two) administered during loading period to estimate cost of the new biologic loading dose.9,16 NNT and cost of effectively clearing one additional patient not achieving complete clearance on initial biologic was determined in the same manner as for the switch to infliximab (Figure 4).
For addition of topical treatment, the added cost was the price of Cal/BD foam when adding topical as an adjunct to the patient’s existing biologic therapy. For the dose escalation approach, the added cost is the same as cost of standard maintenance biologic dosing as we have estimated dose escalation to double the price of standard dose (Figure 3). For the switch to another biologic approach, assuming the maintenance cost of the new biologic is equal to the baseline cost of the initial biologic, the added cost is simply the cost of the new biologic loading dose.
Time to Clearance and Safety
Secondary endpoints include time to clearing and adverse event rates. To determine time to clearing, we evaluated the time (number of weeks) it took patients to achieve psoriasis clearance on different treatments. Lastly, we looked at AE rates as another secondary endpoint and reported serious AE described in the studies to assess safety.
Switching to Another Biologic Approach Cost Considerations
Studies evaluating switching to another biologic approach reporting clearance as PASI 100 or PGA 0 were identified for infliximab and guselkumab only.15,16 Similar to dose escalation approach, the number of subjects in the study and percentage of patients achieving clearance were used to determine NNT to achieve clearance in one additional patient (Figure 1). We assumed that the baseline cost on the first biologic would equal the cost of the switched biologic except the additional cost of loading dose of the new biologic. To determine the additional cost with this approach, we needed to estimate cost of the new biologic loading dose. For infliximab, the loading dose of 5 mg/ kg is administered at weeks 0, 2, and 6. We used the price of reconstituted 100 mg intravenous infliximab solution ($1,167) obtained from Medi-Span Price Rx,9 and the average weight was assumed to be 80 kg, which would require a 400 mg infliximab dose. The cost/unit of medication ($1,167*4 = $4,668) was multiplied by the number of medication units (three) administered during loading period of infliximab: $4,668*3 = $14,004 to estimate cost of the new biologic loading dose. Multiplying this cost by the NNT provides additional cost required to effectively clear one more patient not achieving complete clearance on initial biologic: $14,004 x 6.3 = $88,225 when switching to infliximab (Figure 4).
In the study evaluating switching to guselkumab, patients were administered guselkumab at weeks 0 and 4 during the loading phase after an inadequate response to ustekinumab. We multiplied the cost/unit of medication ($10,859) by the number of medication units (two) administered during loading period to estimate cost of the new biologic loading dose.9,16 NNT and cost of effectively clearing one additional patient not achieving complete clearance on initial biologic was determined in the same manner as for the switch to infliximab (Figure 4).
For addition of topical treatment, the added cost was the price of Cal/BD foam when adding topical as an adjunct to the patient’s existing biologic therapy. For the dose escalation approach, the added cost is the same as cost of standard maintenance biologic dosing as we have estimated dose escalation to double the price of standard dose (Figure 3). For the switch to another biologic approach, assuming the maintenance cost of the new biologic is equal to the baseline cost of the initial biologic, the added cost is simply the cost of the new biologic loading dose.
Time to Clearance and Safety
Secondary endpoints include time to clearing and adverse event rates. To determine time to clearing, we evaluated the time (number of weeks) it took patients to achieve psoriasis clearance on different treatments. Lastly, we looked at AE rates as another secondary endpoint and reported serious AE described in the studies to assess safety.
RESULTS
Complete clearance in those not initially cleared on their biologic was achieved in 28% (n=7) of subjects when adding calcipotriene/ betamethasone dipropionate (Cal/BD) foam, 20% (n=135) of patients switching to guselkumab, and 15.8% (n=179) switching to infliximab (Table 1).15-17 These rates represent clearance beyond what was accomplished by the initial biologic. There were limited data reporting efficacy of dose escalation in patient populations failing an initial biologic; we have estimated around 10.9% patients would achieve clearance with dose doubling of adalimumab, ustekinumab, ixekizumab, and guselkumab.
In addition to patient’s baseline cost of initial biologic, adding a topical agent costs $3,780 per additional patient cleared (Table 1). Adding a topical agent is less costly than biologic dose escalation or switching biologic approaches. Guselkumab is the least costly option for achieving clearance with dose escalation with $73,370 being the added cost of effectively clearing one additional subject, whereas adalimumab is the most costly option at $290,900 per additional patient cleared (Table 2). Switching the initial failed biologic to infliximab ($88,225 per additional patient cleared) is least costly switching intervention; guselkumab was estimated to cost $108,590 per additional patient cleared (Table 1). No other studies were identified that reported complete psoriatic clearance after switching biologics.
Time to clearing was shortest for adding a topical agent approach as patients achieved total clearance of plaque psoriasis as early as week 4.17 Time to clearance for dose escalation would be expected to be more than 24-28 weeks, as it takes 24 weeks to achieve clearance on adalimumab and guselkumab standard dosing, and 28 weeks to reach clearance on ustekinumab and ixekizumab standard dosing (Table 3). Time to clearance with switching to infliximab is 26 weeks while it’s 36 weeks for switching to guselkumab, although we made an assumption in this paper that switch to guselkumab would also clear patients in 26 weeks.15,16
Lastly, serious AE were evaluated as another secondary endpoint to assess safety of treatments. Adding Cal/BD foam is safer than dose escalation or switching to another biologic, as there were no treatment-related AE or serious AE when adding a topical agent to biologic monotherapy.17 AE rates for biologic dose escalation are expected to be at least as high as rates (1.7% – 4.9% serious AE) reported in studies evaluating standard biologic dosing.11-14 3.7% and 6.7% of patients experienced serious AE in studies evaluating switching to infliximab and switching to guselkumab, respectively (Table 3).15,16
In addition to patient’s baseline cost of initial biologic, adding a topical agent costs $3,780 per additional patient cleared (Table 1). Adding a topical agent is less costly than biologic dose escalation or switching biologic approaches. Guselkumab is the least costly option for achieving clearance with dose escalation with $73,370 being the added cost of effectively clearing one additional subject, whereas adalimumab is the most costly option at $290,900 per additional patient cleared (Table 2). Switching the initial failed biologic to infliximab ($88,225 per additional patient cleared) is least costly switching intervention; guselkumab was estimated to cost $108,590 per additional patient cleared (Table 1). No other studies were identified that reported complete psoriatic clearance after switching biologics.
Time to clearing was shortest for adding a topical agent approach as patients achieved total clearance of plaque psoriasis as early as week 4.17 Time to clearance for dose escalation would be expected to be more than 24-28 weeks, as it takes 24 weeks to achieve clearance on adalimumab and guselkumab standard dosing, and 28 weeks to reach clearance on ustekinumab and ixekizumab standard dosing (Table 3). Time to clearance with switching to infliximab is 26 weeks while it’s 36 weeks for switching to guselkumab, although we made an assumption in this paper that switch to guselkumab would also clear patients in 26 weeks.15,16
Lastly, serious AE were evaluated as another secondary endpoint to assess safety of treatments. Adding Cal/BD foam is safer than dose escalation or switching to another biologic, as there were no treatment-related AE or serious AE when adding a topical agent to biologic monotherapy.17 AE rates for biologic dose escalation are expected to be at least as high as rates (1.7% – 4.9% serious AE) reported in studies evaluating standard biologic dosing.11-14 3.7% and 6.7% of patients experienced serious AE in studies evaluating switching to infliximab and switching to guselkumab, respectively (Table 3).15,16
