Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis

Abstract

Objective: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care.

Method: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses.

Results: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%.

Conclusion: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

Keywords: Cost-efficacy; Gabapentin; Knee osteoarthritis; Pain.

Figure 1

Panel A. The usual care, gabapentin sparing (UC-GS) treatment sequence for knee OA in the OAPol model. Subjects are initialized based on specific cohort characteristics and progress through the regimens outlined, including an NSAID plus corticosteroid injections, tramadol, opioids (for some subjects, others skip the tramadol and opioid regimens), total knee replacement, and revision total knee replacement. Subjects remain on each treatment until it is no longer effective. Death can occur at any point in the sequence. Panel B. The targeted gabapentin (TG) treatment sequence for knee OA in the OAPol model. Subjects are initialized based on specific cohort characteristics and are screened for nociplastic pain using the modified PainDETECT questionnaire (mPD-Q) at initialization. If they screen positive for nociplastic pain, they receive gabapentin in addition to an NSAID plus corticosteroid injections before moving on to the rest of the UC treatment sequence of tramadol, opioids (for some subjects, others skip the tramadol and opioid regimens), total knee replacement, and revision total knee replacement. If they screen negative for nociplastic pain, they proceed normally through the UC sequence. Subjects remain on each treatment until it is no longer effective. Death can occur at any point in the sequence. Panel C. The universal gabapentin treatment sequence for knee OA in the OAPol model. Subjects are initialized based on specific cohort characteristics and receive gabapentin in addition to an NSAID plus corticosteroid injections before moving on to the rest of the UC treatment sequence of tramadol, opioids (for some subjects, others skip the tramadol and opioid regimens), total knee replacement, and revision total knee replacement. Subjects remain on each treatment until it is no longer effective. Death can occur at any point in the sequence.

Figure 2

Panel A. Bivariate heat map of the modified PainDETECT questionnaire (mPD-Q) sensitivity and adverse event (AE) rate for the targeted gabapentin (TG) strategy. The AE rate refers to the likelihood of experiencing one of the three AEs (drug abuse/misuse, overdose, suicidal behavior, and deaths) that lead to immediate discontinuation of gabapentin. Incremental cost-effectiveness ratios (ICERs) for the TG strategy were calculated for increasing mPD-Q sensitivity values and decreasing AE rates. The AE rate was decreased from the base case value of 10% to 0% and the mPD-Q sensitivity was increased from the base case value of 58% to 100%. All other parameters were held at base case values. ICERs were categorized into buckets and assigned an orange color as specified in the key. Panel B. Bivariate heat map of the modified PainDETECT questionnaire (mPD-Q) specificity and adverse event rate for the targeted gabapentin (TG) strategy. The AE rate refers to the likelihood of experiencing one of the three AEs (drug abuse/misuse, overdose, suicidal behavior, and deaths) that lead to immediate discontinuation of gabapentin. Incremental cost-effectiveness ratios (ICERs) for the TG strategy were calculated for increasing mPD-Q specificity values and decreasing AE rates. The AE rate was decreased from the base case value of 10% to 0% and the mPD-Q specificity was increased from the base case value of 71% to 100%. All other parameters were held at base case values. ICERs were categorized into buckets and assigned an orange color as specified in the key. Panel C. Bivariate heat map of gabapentin efficacy and adverse event rate for the targeted gabapentin strategy. The AE rate refers to the likelihood of experiencing one of the three AEs (drug abuse/misuse, overdose, suicidal behavior, and deaths) that lead to immediate discontinuation of gabapentin. Incremental cost-effectiveness ratios (ICERs) for the TG strategy were calculated for increasing gabapentin efficacy values and decreasing AE rates. The AE rate was decreased from the base case value of 10% to 0% and gabapentin efficacy was increased from the base case value of 40.6% to 60% nociplastic pain reduction.

Figure 3

The cost-effectiveness points distribution corresponding to the probabilistic sensitivity analyses that were conducted varying gabapentin efficacy, nociplastic prevalence, discontinuation rates, mPD-Q sensitivity and specificity, AE rates and AE QoL multipliers. One thousand sets of probabilistically chosen inputs were drawn from plausible distributions. Each point in the plane marks the average lifetime medical cost and average cumulative quality adjusted life years for a single strategy from one of the 1,000 model runs in the probabilistic sensitivity analysis. Lifetime medical costs are reported in 2020 USD and treatment efficacy is reported in quality adjusted life years. The three treatment strategies include usual care (UC), universal gabapentin (UG), and targeted gabapentin (TG).

Figure 4

Probabilistic sensitivity analyses were conducted varying gabapentin efficacy, nociplastic prevalence, discontinuation rates, mPD-Q sensitivity and specificity, AE rates and AE QoL multipliers. 1,000 iterations of probabilistically chosen inputs were drawn. Incremental cost-effectiveness ratios (ICERs) were calculated for each iteration comparing the usual care, gabapentin sparing (green line), targeted gabapentin (orange line), and universal gabapentin (purple line) treatment strategies. The ICERs for these strategies were compared at a range of willingness-to-pay (WTP) thresholds, and that which produced the greatest number of quality-adjusted life years while remaining below the WTP threshold was termed the preferred strategy. The probability of being the preferred strategy is plotted against WTP thresholds from $0 to $200,000/QALY.