Aetna considers tofacitinib (Xeljanz), alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs), medically necessary for the treatment of adults with moderately-to-severely active rheumatoid arthritis (RA) (see note) who have had an inadequate response to, or who are intolerant of, methotrexate when the following criteria are met:

• A documented recent tuberculin skin test (within 6 months) to check for latent tuberculosis; and
• A documented contraindication or intolerance or allergy or inadequate response to a trial of 1 month each of 2 least cost medically necessary alternatives indicated for RA.

Note: There are several brands of targeted immune modulators on the market.  There is a lack of reliable evidence that any one brand of targeted immune modulator is superior to other brands for medically necessary indications.  Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Simponi (golimumab), Simponi Aria (golimumab intravenous) and Stelara (ustekinumab) brands of targeted immune modulators ("least cost brands of targeted immune modulators") are less costly to Aetna.  Consequently, because other brands (e.g., Actemra (tocilizumab), Cimzia (certolizumab), Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), and Xeljanz (tofacitinib)) of injectables are more costly than these least cost brands of targeted immune modulators, and least cost brands of targeted immune modulators are at least as likely to produce equivalent therapeutic results, no other brands of targeted immune modulator will be considered medically necessary unless the member has a contraindication, intolerance or incomplete response to at least 2 of the least cost brands of targeted immune modulator: Enbrel, Humira, Remicade, Simponi, Simponi Aria, or Stelara, for the same medically necessary indication. If the least costly targeted immune modulator does not have the labeled indication (see appendix), then Aetna considers medically necessary another brand of targeted immune modulator that has the required labeling indication.

Aetna considers tofacitinib in combination with biologic DMARDs (e.g., adalimumab and etanercept) or potent immunosuppressants (e.g., azathioprine and cyclosporine) for the treatment of RA experimental and investigational because the effectiveness of this approach has not been established.

Aetna considers tofacitinib experimental and investigational for the following diseases/conditions (not an all-inclusive list) because its effectiveness for these indications has not been established:

• Dry eye disease
• Inflammatory bowel diseases (Crohn's disease and ulcerative colitis)
• Prevention of organ transplant rejection
• Psoriasis
• Psoriatic arthritis

See also: CPB 0314 - Rituximab (Rituxan); CPB 0315 - Enbrel (Etanercept); CPB 0341 - Remicade (infliximab); CPB 0595 - Kineret (Anakinra); CPB 0655 - Adalimumab (Humira); CPB 0720 - Abatacept (Orencia); CPB 0761 - Certolizumab Pegol (Cimzia); CPB 0790 - Golimumab (Simponi); CPB 0799 - Tocilizumab (Actemra); and CPB 0818 - Belimumab (Benlysta).

Currently available therapeutic options for rheumatoid arthritis (RA) entail disease-modifying anti-rheumatic drugs (DMARDs; e.g., anti-malarials, cyclosporine, gold compounds, methotrexate, or sulfasalazine), and biologic agents (e.g., adalimumab, abatacept, anakinra, etanercept, infliximab, rituximab, and tocilizumab).  However, these treatments often fail to adequately prevent disease progression.  Tofacitinib is an inhibitor of the enzyme Janus kinase 3 (JAK3), which means that it interferes with the JAK-STAT signaling pathway that plays an important role in the pathogenesis of RA.  Tofacitinib has been evaluated in phase II and phase III studies, as both monotherapy and in combination with methotrexate (MTX) and other DMARDs, and demonstrated improvements in the signs and symptoms of RA, patient health, physical functioning as well as quality of life, while having a manageable safety profile (de Lartigue, 2012). 

In a 12-week, phase II, double-blind study, Tanaka et al (2011) compared the efficacy, safety, and tolerability of 4 doses of oral tofacitinib with placebo in Japanese patients with active RA receiving stable background MTX who had an inadequate response to MTX alone.  A total of 140 patients were randomized to receive tofacitinib 1, 3, 5, and 10 mg twice-daily or placebo in this study.  All patients remained on background MTX.  Efficacy and safety were assessed at weeks 1, 2, 4, 8, and 12.  The primary efficacy end point was the American College of Rheumatology 20 % improvement criteria (ACR20) response rate at week 12.  ACR20 response rates at week 12 were significant (p < 0.0001) for all tofacitinib treatment groups: 1 mg twice-daily, 64.3 %; 3 mg twice-daily, 77.8 %; 5 mg twice-daily, 96.3 %; and 10 mg twice-daily, 80.8 % versus placebo, 14.3 %.  A significant dose-response relationship for the ACR20 was observed (p < 0.0001).  Low disease activity was achieved by 72.7 % of patients with high baseline disease activity for tofacitinib 10 mg twice-daily at week 12 (p < 0.0001).  Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index (HAQ-DI) score, and 3-variable Disease Activity Score in 28 joints (DAS28) using C-reactive protein (DAS28-3[CRP]) were also reported.  The most commonly reported adverse events (AEs) were naso-pharyngitis (n = 13) and increased alanine aminotransferase (n = 12) and aspartate aminotransferase (n = 9) levels.  These AEs were mild or moderate in severity.  Serious AEs were reported by 5 patients; no deaths occurred.  The authors concluded that in Japanese patients with active RA with an inadequate response to MTX, tofacitinib in combination with MTX over 12 weeks was effective and had a manageable safety profile.

In a 24-week, double-blind, phase IIb study, Fleischmann et al (2012a) compared the efficacy, safety, and tolerability of 5 doses of oral tofacitinib or adalimumab monotherapy with placebo for the treatment of active RA in patients with an inadequate response to DMARDs.  Patients with RA (n = 384) were randomized to receive placebo, tofacitinib at 1, 3, 5, 10, or 15 mg administered orally twice-daily, or adalimumab at 40 mg injected subcutaneously every 2 weeks (total of 6 injections) followed by oral tofacitinib at 5 mg twice-daily for 12 weeks.  The primary end point was the responder rate according to ACR20 at week 12.  Treatment with tofacitinib at a dose of greater than or equal to 3 mg twice-daily resulted in a rapid response with significant efficacy when compared to placebo, as indicated by the primary end point (ACR20 response at week 12), achieved in 39.2 % (3 mg; p ≤ 0.05), 59.2 % (5 mg; p < 0.0001), 70.5 % (10 mg; p < 0.0001), and 71.9 % (15 mg; p < 0.0001) in the tofacitinib group and 35.9 % of patients in the adalimumab group (p = 0.105), compared with 22.0 % of patients receiving placebo.  Improvements were sustained at week 24, according to the ACR20, ACR50, and ACR70 response rates as well as classifications of remission according to the 3-variable Disease Activity Score in 28 joints (DAS28) using C-reactive protein (DAS28-3[CRP]) and the 4-variable DAS28 using the erythrocyte sedimentation rate (DAS28-4[ESR]).  The most common treatment-related AEs in patients across all tofacitinib treatment arms (n = 272) were urinary tract infection (7.7 %), diarrhea (4.8 %), headache (4.8 %), and bronchitis (4.8 %).  The authors concluded that tofacitinib monotherapy at greater than or equal to 3 mg twice-daily was effective in the treatment of patients with active RA over 24 weeks and demonstrated a manageable safety profile.

In a 24-week, double-blind, phase IIb study, Kremer et al (2012) compared the efficacy, safety, and tolerability of 6 doses of oral tofacitinib with placebo for the treatment of active RA in patients receiving a stable background regimen of MTX who have an inadequate response to MTX monotherapy.  Patients with active RA (n = 507) were randomized to receive placebo or tofacitinib (20 mg/day, 1 mg twice-daily, 3 mg twice-daily, 5 mg twice-daily, 10 mg twice-daily, or 15 mg twice-daily).  All patients continued to receive a stable dosage of MTX.  The primary end point was the ACR20 response rate at week 12.  At week 12, ACR20 response rates for patients receiving all tofacitinib dosages greater than or equal to 3 mg twice-daily (52.9 % for 3 mg twice-daily, 50.7 % for 5 mg twice-daily, 58.1 % for 10 mg twice-daily, 56.0 % for 15 mg twice-daily, and 53.8 % for 20 mg/day) were significantly (p ≤ 0.05) greater than those for placebo (33.3 %).  Improvements were sustained at week 24 for the ACR20, ACR50, and ACR70 responses, scores for the HAQ-DI scores, the DAS28-3[CRP], and a 3-variable DAS28-3[CRP] of less than 2.6.  The most common treatment-related AEs occurring in greater than 10 % of patients in any tofacitinib group were diarrhea, upper respiratory tract infection, and headache; 21 patients (4.1 %) experienced serious AEs.  Sporadic increases in transaminase levels; increases in cholesterol and serum creatinine levels; and decreases in neutrophil and hemoglobin levels were observed.  The authors concluded that in patients with active RA in whom the response to MTX has been inadequate, the addition of tofacitinib at a dosage greater than or equal to 3 mg twice-daily showed sustained efficacy and a manageable safety profile over 24 weeks.

In a phase III, double-blind, placebo-controlled, parallel-group, 6-month study, (Fleischmann et al, 2012b), a total of 611 patients were randomly assigned in a 4:4:1:1 ratio to 5 mg of tofacitinib twice-daily, 10 mg of tofacitinib twice-daily, placebo for 3 months followed by 5 mg of tofacitinib twice-daily, or placebo for 3 months followed by 10 mg of tofacitinib twice-daily.  The primary end points, assessed at month 3, were the percentage of patients with at least a 20 % improvement in the ACR 20, the change from baseline in HAQ-DI scores (which ranged from 0 to 3, with higher scores indicating greater disability), and the percentage of patients with a DAS28-joint counts based on DAS28-4[ESR] of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating more disease activity).  At month 3, a higher percentage of patients in the tofacitinib groups than in the placebo groups met the criteria for an ACR 20 response (59.8 % in the 5-mg tofacitinib group and 65.7 % in the 10-mg tofacitinib group versus 26.7 % in the combined placebo groups, p < 0.001 for both comparisons).  The reductions from baseline in HAQ-DI scores were greater in the 5-mg and 10-mg tofacitinib groups than in the placebo groups (-0.50 and -0.57 points, respectively, versus -0.19 points; p < 0.001).  The percentage of patients with a DAS28-4(ESR) of less than 2.6 was not significantly higher with tofacitinib than with placebo (5.6 % and 8.7 % in the 5-mg and 10-mg tofacitinib groups, respectively, and 4.4 % with placebo; p = 0.62 and p = 0.10 for the two comparisons).  Serious infections developed in 6 patients who were receiving tofacitinib.  Common AEs were headache and upper respiratory tract infection.  Tofacitinib treatment was associated with elevations in low-density lipoprotein cholesterol levels and reductions in neutrophil counts.  The authors concluded that in patients with active RA, tofacitinib monotherapy was associated with reductions in signs and symptoms of RA and improvement in physical function.

van Vollenhoven et al (2012) compared tofacitinib and adalimumab in the treatment of RA.  In this 12-month, phase III clinical trial, a total of 717 patients who were receiving stable doses of MTX were randomly assigned to 5 mg of tofacitinib twice-daily, 10 mg of tofacitinib twice-daily, 40 mg of adalimumab once every 2 weeks, or placebo.  At month 3, patients in the placebo group who did not have a 20 % reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice-daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion.  The 3 primary outcome measures were a 20 % improvement at month 6 in the ACR 20; the change from baseline to month 3 in the score on the HAQ-DI (which ranged from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a DAS28-4[ESR] of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity).  At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5 % and 52.6 %, respectively) and among those receiving adalimumab (47.2 %) than among those receiving placebo (28.3 %) (p < 0.001 for all comparisons).  There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group.  Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in 2 patients in the 10-mg tofacitinib group.  Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts.  The authors concluded that in patients with RA receiving background MTX, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy.

On November 6, 2012, the Food and Drug Administration (FDA) approved tofacitinib (Xeljanz) for the treatment of adults with moderately-to-severely active RA who have had an inadequate response to, or who are intolerant of, MTX.  The FDA approved tofacitinib with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a Medication Guide advising patients about important safety information and a communication plan to inform health care providers about the serious risks associated with tofacitinib.  To study the long-term effects of tofacitinib on heart disease, cancer, and serious infections, the FDA is requiring a post-marketing study that will evaluate 2 doses of tofacitinib and include a group of patients on another approved treatment to serve as a comparison.  The use of tofacitinib was associated with an increased risk of serious infections, including opportunistic infections, tuberculosis, cancers and lymphoma.  The most common AEs in clinical trials were upper respiratory tract infections, headache, diarrhea, and inflammation of the nasal passage and the upper part of the pharynx.  According to the Prescribing Information of Xeljanz, it may be used as monotherapy or in combination with MTX or other non-biologic DMARDs.  Furthermore, Xeljanz should not be used in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine.

Tofacitinib is also being investigated in the treatment of dry eye disease, inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and plaque psoriasis as well as prevention of organ transplant rejection.  However, its effectiveness for these diseases/conditions has not been established.

In a phase I/II prospective, randomized, vehicle- and comparator-controlled clinical trial, Huang et al (2012) evaluated the immuno-modulatory effect of topical ophthalmic tofacitinib after an 8-week treatment period in patients with dry eye disease (DED).  A total of 82 patients with moderate-to-severe DED enrolled in this study.  Patients received 1 of 5 doses of tofacitinib (0.0003 %, 0.001 %, 0.003 %, or 0.005 % twice-daily [BID] or 0.005 % once-daily [QD]), active comparator (cyclosporine ophthalmic emulsion, 0.05 % [Restasis]), or vehicle control BID for 8 weeks.  Conjunctival impression cytology and tear fluid samples were collected at baseline and after an 8-week treatment period.  Conjunctival cells were analyzed by flow cytometry for human leukocyte antigen DR-1 (HLA-DR).  Tear fluids were analyzed by microsphere-based immunoassays for tear levels of cytokines and inflammation markers.  Main outcome measures were reduction in inflammation assessed by change from baseline in conjunctival cell surface level of HLA-DR and tear level of cytokines and inflammation markers.  At week 8, a decrease in conjunctival cell surface expression of HLA-DR was observed in patients treated with tofacitinib 0.005 % QD and 0.003 % BID: 71 % and 67 % of baseline, respectively, compared with 133 % of baseline in patients treated with vehicle (p = 0.023 and p = 0.006, compared with vehicle, respectively).  Matrix metallo-proteinase (MMP)-3 in tears was reduced from baseline at week 8 (40 % of baseline, p = 0.035) in the tofacitinib 0.005 % QD group, whereas the vehicle group showed 77 % of baseline (p > 0.20).  Interleukin (IL)-1β in tears was 36 % of baseline (p = 0.053) in the tofacitinib 0.005 % QD group and 95 % of baseline (p > 0.20) in the vehicle group.  Several other cytokines and inflammation markers in tears, including MMP-9, IL-15, IL-17A, and IL-12p70, were markedly reduced in the tofacitinib 0.005 % QD group but not the vehicle group.  There was an association between the changes in HLA-DR and the tear inflammation markers (p < 0.05): HLA-DR with IL-12p70 (r = 0.49) and IL-1β (r = 0.46), IL-12p70 with IL-1β (r = 0.90), and IL-17A with MMP-9 (r = 0.82).  The authors concluded that topical ophthalmic tofacitinib may act as an immuno-modulator in patients with DED.  Treatment for 8 weeks showed a promising reduction of conjunctival cell surface HLA-DR expression and tear levels of pro-inflammatory cytokines and inflammation markers.  These preliminary findings need to be validated by well-designed studies.

Perrier and Rutgeerts (2012) stated that several anti-tumor necrosis factor-alpha agents are currently used to treat Crohn's disease and ulcerative colitis.  Although these agents have markedly improved the treatment of inflammatory bowel diseases, up to 50 % of the patients have no sustained benefit due to non-response, loss of response or intolerance.  Novel therapies targeting other immune pathways are under study, such as antibodies targeting the IL-12/IL-23 pathway, and have shown interesting preliminary results.  In parallel, anti-adhesion therapies limiting the recruitment of cells to the gut will reach the clinic in the coming years.  Small molecules inhibiting the production of pro-inflammatory cytokines are already used in the clinic for RA, and tofacitinib appears to have great potential to treat ulcerative colitis.

Papp et al (2012) noted that tofacitinib is a novel, oral Janus kinase inhibitor under investigation as a potential treatment for plaque psoriasis.  In a phase IIb, 12-week, dose-ranging study, these researchers characterized the exposure-response, safety and effectiveness of tofacitinib versus placebo in patients with moderate-to-severe chronic plaque psoriasis.  A total of 197 patients were randomized.  The primary end point was the proportion of patients achieving a greater than or equal to 75 % reduction in the Psoriasis Area and Severity Index (PASI 75) score at week 12.  At week 12, PASI 75 response rates were significantly higher for all tofacitinib twice-daily groups: 25.0 % (2 mg; p < 0.001), 40.8 % (5 mg; p < 0.0001) and 66.7 % (15 mg; p < 0.0001), compared with placebo (2.0 %).  Significant increases in the proportion of PASI 75 responses were observed by week 4 and were maintained at week 12.  Exposure-response over the 0 to 15 mg tofacitinib twice-daily dose range was successfully characterized.  PASI 50, PASI 90 and Physician's Global Assessment response rates were also higher for tofacitinib versus placebo.  The most frequently reported AEs were infections and infestations: 22.4 % (2 mg twice-daily), 20.4 % (5 mg twice-daily), 36.7 % (15 mg twice-daily) and 32.0% (placebo).  Discontinuations due to AEs were 6.0 %, 2.0 %, 4.1 % and 6.1 % of patients in the placebo, 2, 5 and 15 mg twice-daily tofacitinib groups, respectively.  Dose-dependent increases from baseline in mean serum high-density lipoprotein, low-density lipoprotein and total cholesterol, and decreases in hemoglobin and neutrophils were observed.  The authors concluded that the short-term treatment with oral tofacitinib results in significant clinical improvement in patients with moderate-to-severe plaque psoriasis and is generally well-tolerated.  These promising findings need to be validated in prospective, randomized, controlled trials with longer follow-up periods.

Charpentier et al (2011) stated that medium- and long-term renal graft survival depends on 4 main factors: (i) the quality of the harvested graft, (ii) ischemia-reperfusion injury during harvesting and re-implantation, (iii) rejection, and (iv) the nephrotoxicity of certain drugs (especially immunosuppressants) used in this setting.  The most nephrotoxic immunosuppressive drugs are the anti-calcineurins (cyclosporine A and tacrolimus), a class discovered in the late 1970s and currently representing a basic component of all immunosuppressive protocols for solid organ graft recipients.  The renal tubular and vascular toxicity of anti-calcineurins is due to their immunosuppressive mechanism: they block the calcineurin pathway and thereby prevent transmission of the first signal from the T cell receptor to the nucleus, which normally triggers cytokine synthesis.  New non-nephrotoxic immunosuppressants are therefore needed, especially for grafts of poor quality or subject to severe ischemia-reperfusion injury.  Attention is turning to "old" molecules such as anti-thymocyte globulins, but exciting new immunosuppressants are now appearing.  Alefacept is a fusion protein that binds to the immunological synapse-associated molecule CD2, which normally interacts with LFA-3.  Belatacept, another fusion protein, blocks the T cell second signal CD 28-B7.1/B7.2.  Finally, new chemical agents are being developed, such as sautrasporine, a tyrosine kinase inhibitor, and tofacitinib, an JAK inhibitor.

Wojciechowski and Vincenti (2011) discussed the mechanism of action and important clinical trial data in renal transplantation for tofacitinib, formerly known as CP-690,550 and tasocitinib.  JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, especially members of the cytokine receptor common gamma chain family.  JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated efficacy in autoimmune disorders such as RA.  Non-human primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared with vehicle control.  Renal transplant clinical trials in humans have demonstrated tofacitinib to be non-inferior to cyclosporine in terms of rejection rates and graft survival.  There was also a lower rate of new-onset diabetes after transplant.  However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis.  The authors concluded that tofacitinib may be a promising alternative to calcineurin inhibitors.  Moreover, the optimal therapeutic window is still being determined.

Wojciechowski and Vincenti (2013) discussed the mechanism of action and important kidney transplant clinical trial data for tofacitinib.  Current maintenance immunosuppressive protocols that rely on calcineurin inhibitors have long-term nephrotoxicity and negative impact on cardio-metabolic risk factors.  JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated effectiveness in autoimmune disorders such as RA.  Non-human primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared to control.  Renal transplant clinical trials in humans have demonstrated tofacitinib to be non-inferior to cyclosporine in terms of rejection rates and graft survival.  There was also a lower rate of new onset diabetes after transplant.  However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis.  The authors concluded that tofacitinib may be a promising alternative to calcineurin inhibitors; and the optimal therapeutic window is still being determined.

In a phase IIa clinical trial, Ports et al (2013) evaluated the safety, effectiveness, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis.  Two tofacitinib ointment formulations were evaluated in this multi-center, double-blind, vehicle-controlled trial.  A total of 71 patients were randomized 2 : 1 : 2 : 1 to 2 % tofacitinib ointment 1, vehicle 1, 2 % tofacitinib ointment 2 and vehicle 2, each administered twice-daily for 4 weeks to a single fixed 300 cm(2) treatment area containing a target plaque with or without 1 or more non-target plaques and normal skin.  The primary end-point of percentage change from baseline in the Target Plaque Severity Score at week 4 demonstrated statistically significant improvement for ointment 1 [least squares mean (LSM) -54.4 %] versus vehicle 1 (LSM -41.5 %), but not ointment 2 (LSM -24.2 %) versus vehicle 2 (LSM -17.2 %).  Secondary end-points (target plaque area and Itch Severity Item) improved similarly for tofacitinib ointment versus corresponding vehicle.  Adverse event occurrence was similar across treatment groups.  All AEs were mild or moderate and none was serious or led to subject discontinuation.  One application-site AE (erythema) was reported.  Tofacitinib mean systemic exposure was minimal and was greater for ointment 1 than for ointment 2.  The authors concluded that tofacitinib ointment 1 was well-tolerated and effective compared with vehicle for the treatment of plaque psoriasis.  Moreover, they stated that further study of topical tofacitinib for psoriasis treatment is warranted.

Gan and colleagues (2013) stated that psoriatic arthritis affects approximately 6 to 42 % of patients with psoriasis.  It is useful for physicians or dermatologists managing psoriasis patients to be aware of how to concurrently manage the joint manifestations, as it is preferable and convenient to use a single agent in such patients.  However, only certain therapies are effective for both.  Systemic agents, which can be used for both skin and joint manifestations, include methotrexate and cyclosporine.  For the group of biologic agents, the tumor necrosis factor inhibitors such as adalimumab, certolizumab, etanercept, golimumab, and infliximab are effective.  Ustekinumab is a more recently developed agent belonging to the group of anti-IL-12p40 antibodies and has been shown to be effective.  Newer drugs in the treatment armamentarium that have shown efficacy for both psoriasis and psoriatic arthritis consist of the anti-IL-17 agent, secukinumab, and a phosphodiesterase-4 inhibitor, apremilast.  The other anti-IL-17 agents, ixekizumab and brodalumab, as well as the oral JAK inhibitor, tofacitinib, have very limited but promising data.

Appendix